Inhixa

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 
  



 

2 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 2,000 IU (20 mg)/0.2 mL solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

10,000 IU/mL (100 mg/mL) solution for injection 

 

Each pre-filled syringe contains enoxaparin sodium 2,000 IU anti-Xa activity (equivalent to 20 mg) in 

0.2 mL water for injections. 

 

For the full list of excipients, see section 6.1. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerization of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in pre-filled syringe. 

Clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in particular 
those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility at 

increased risk of venous thromboembolism.  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to require 
thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), in 

combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to be 
managed medically or with subsequent percutaneous coronary intervention (PCI). 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 



 

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 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous (SC) injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk surgery.  

In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 7-

10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the patient no 

longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by SC injection preferably started 12 hours before surgery. If there is a need for 

earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high risk patient 

waiting for a deferred orthopaedic surgery), the last injection should be administered no later than 

12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis 
up to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal 
or pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by SC injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status (e.g. 

mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered SC either as a once daily injection of 150 IU/kg (1.5 mg/kg) or as 

twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by SC injection administered in combination with antiplatelet 

therapy. Treatment should be maintained for a minimum of 2 days and continued until clinical 

stabilization. The usual duration of treatment is 2 to 8 days.  

Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading 

dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75–325 mg/day 

long-term regardless of treatment strategy. 



 

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 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous (IV) 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) SC dose followed by 100 IU/kg (1 mg/kg) 

administered SC every 12 hours (maximum 10,000 IU (100 mg) for each of the first two SC doses). 

Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg to 325 mg once daily) should be 

administered concomitantly unless contraindicated. The recommended duration of treatment is 8 days or 

until hospital discharge, whichever comes first. When administered in conjunction with a thrombolytic 

(fibrin specific or non-fibrin specific), enoxaparin sodium should be given between 15 minutes before 

and 30 minutes after the start of fibrinolytic therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last dose of enoxaparin sodium SC was given less than 

8 hours before balloon inflation, no additional dosing is needed. If the last SC administration 

was given more than 8 hours before balloon inflation, an IV bolus of 30 IU/kg (0.3 mg/kg) 

enoxaparin sodium should be administered. 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established. 

 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below “renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥75 years of age, an initial IV bolus must not be used. 

Initiate dosing with 75 IU/kg (0.75 mg/kg) SC every 12 hours (maximum 7,500 IU (75 mg) for each of the 

first two SC doses only, followed by 75 IU/kg (0.75 mg/kg) SC dosing for the remaining doses). For dosage 

in elderly patients with impaired kidney function, see below “renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

 Severe renal impairment  
Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease  

 

2,000 IU (20 mg) SC once daily 

Treatment of  DVT and PE 100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of acute STEMI (patients under 75) 

 

 

 

Treatment of acute STEMI (patients over 75) 

1 x 3,000 IU (30 mg) IV bolus plus 100 IU/kg 

(1 mg/kg) body weight SC and then 100 IU/kg 

(1 mg/kg) body weight SC every 24 hours 

 

No IV initial bolus, 100 IU/kg (1 mg/kg) body 

weight SC and then 100 IU/kg (1 mg/kg) body 

weight SC every 24 hours 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

 Moderate and mild renal impairment 



 

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Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30-

50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring is 

advised. 

 

Method of administration  

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thrombo-embolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by SC injection. 

 For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a 
SC injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The pre-filled disposable syringe is ready for immediate use.  

 

The use of a tuberculin syringe or equivalent is recommended when using ampoules or multiple-dose vials to 

assure withdrawal of the appropriate volume of drug. 

 

 SC injection technique: 
Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep SC injection.  

 

Do not expel the air bubble from the syringe before the injection to avoid the loss of drug when using pre-

filled syringes. When the quantity of drug to be injected requires to be adjusted based on the patient’s body 

weight, use the graduated pre-filled syringes to reach the required volume by discarding the excess before 

injection. Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations 

on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. Do not rub the 

injection site after administration. 

 

Note for the pre-filled syringes fitted with an automatic safety system: The safety system is triggered at the 

end of the injection (see instructions in section 6.6). 

 

In case of self-administration, patient should be advised to follow instructions provided in the patient 

information leaflet included in the pack of this medicine. 

 

 IV (bolus) injection (for acute STEMI indication only): 
For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a SC 

injection.  

For IV injection, either the multidose vial or pre-filled syringe can be used. 

Enoxaparin sodium should be administered through an IV line. It should not be mixed or co-administered 

with other medications. To avoid the possible mixture of enoxaparin sodium with other drugs, the IV access 

chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the IV 

bolus administration of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely 

administered with normal saline solution (0.9%) or 5% dextrose in water. 

 

o Initial 3,000 IU (30 mg) bolus 



 

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For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the IV line. 

 

o Additional bolus for PCI when last SC administration was given more than 8 hours before balloon 
inflation 

For patients being managed with PCI, an additional IV bolus of 30 IU/kg (0.3 mg/kg) is to be administered if 

last SC administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either normal saline solution (0.9%) or 5% 

dextrose in water) as follows:  

Withdraw 30 mL from the infusion bag with a syringe and discard the liquid. Inject the complete contents of 

the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe into the 20 mL remaining in the bag. Gently mix 

the contents of the bag. Withdraw the required volume of diluted solution with a syringe for administration 

into the IV line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 



 

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Volume to be injected through IV line after dilution is completed at a concentration of 300 IU (3 mg) /mL. 

 

Weight 

 

Required dose 

 30 IU/kg (0.3 mg/kg) 

Volume to inject when 

diluted to a final 

concentration of  

 300 IU (3 mg) / mL 

 

[kg] 

 

IU 

 

[mg] 

 

[mL] 

 

45 

 

1350 

 

13.5 

 

4.5 

50 1500 15 5 

55 1650 16.5 5.5 

60 1800 18 6 

65 1950 19.5 6.5 

70 2100 21 7 

75 2250 22.5 7.5 

80 2400 24 8 

85 2550 25.5 8.5 

90 2700 27 9 

95 2850 28.5 9.5 

100 3000 30 10 

105 3150 31.5 10.5 

110 3300 33 11 

115 3450 34.5 11.5 

120 3600 36 12 

125 3750 37.5 12.5 

130 3900 39 13 

135 4050 40.5 13.5 

140 4200 42 14 

145 4350 43.5 14.5 

150 4500 45 15 

  

 

 Arterial line injection: 
It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 

Switch between enoxaparin sodium and oral anticoagulants 

 Switch between enoxaparin sodium and vitamin K antagonists (VKA)  
Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalized 

Ratio (INR)] must be intensified to monitor the effect of VKA. 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

 Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 
For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 



 

8 

 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

- At doses used for prophylaxis 
A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin 

sodium at prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing 

the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with 

neuraxial anaesthesia. 

- At doses used for treatment 
A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin 

sodium at curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg 

(1 mg/kg) twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay 

before catheter placement or removal.  

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH) or to any of the excipients listed in section 6.1; 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

 

4.4 Special warnings and precautions for use 
 

 General 
Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

 History of HIT (>100 days) 



 

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Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-

induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such a 

case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments 

are considered (e.g. danaparoid sodium or lepirudin). 

 

 Monitoring of platelet counts 
The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 

 

 Haemorrhage 
As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 
- neuro- or ophthalmologic surgery, 
- concomitant use of medications affecting haemostasis (see section 4.5). 

 

 Laboratory tests 
At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

 Spinal/Epidural anaesthesia or lumbar puncture 
Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 



 

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To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach a 

sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance [15--

30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is more 

prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

 Skin necrosis / cutaneous vasculitis 
Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

 Percutaneous coronary revascularization procedures 
To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If the treatment with 

enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours 

after sheath removal. The site of the procedure should be observed for signs of bleeding or hematoma 

formation. 

 

 Acute infective endocarditis 
Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after a 

careful individual benefit risk assessment. 

 

 Mechanical prosthetic heart valves 
The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 

 Pregnant women with mechanical prosthetic heart valves 
The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg ) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

 Elderly 
No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 



 

11 

 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

 Renal impairment 
In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which increases the 

risk of bleeding. In these patients, careful clinical monitoring is advised, and biological monitoring by anti-

Xa activity measurement might be considered (see sections 4.2 and 5.2). 

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 

 Hepatic impairment 
Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

 Low weight 
An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

 Obese Patients 
Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI >30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 

 

 Hyperkalaemia 
Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  

 Traceability 
LMWHs are biological medicinal products. In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded. 

  

Sodium content 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended:  

 Medicinal products affecting haemostasis (see section 4.4) 
It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 



 

12 

 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 

 

Concomitant use with caution: 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

 Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  

- Systemic glucocorticoids. 
 

 Medicinal products increasing potassium levels: 
Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 

Breast-feeding  

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely. Inhixa can be used during breastfeeding. 

 

Fertility 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 



 

13 

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) SC once daily for prophylaxis of deep vein thrombosis 

following surgery or in acutely ill medical patients with severely restricted mobility. In treatment of DVT 

with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg (1 mg/kg) SC 

dose every 12 hours or a 150 IU/kg (1.5 mg/kg) SC dose once a day. In the clinical studies for treatment of 

unstable angina and non-Q-wave myocardial infarction, doses were 100 IU/kg (1 mg/kg) SC every 12 hours, 

and in the clinical study for treatment of acute STEMI enoxaparin sodium regimen was a 3,000 IU (30 mg) 

IV bolus followed by 100 IU/kg (1 mg/kg) SC every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see section 4.4 and 'Description of selected adverse reactions' below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 

1/1000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

 Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 

 Rare: Eosinophilia* 

 Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 
complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

 Common: Allergic reaction 

 Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

 Common: Headache* 
 

Vascular disorders 

 Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees of 
neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 

 Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of normality) 

 Uncommon: Hepatocellular liver injury *  

 Rare: Cholestatic liver injury* 
 

Skin and subcutaneous tissue disorders 

 Common: Urticaria, pruritus, erythema  

 Uncommon: Bullous dermatitis 

 Rare: Alopecia* 

 Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena have 
been usually preceded by purpura or erythematous plaques, infiltrated and painful). 

Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 

resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

 Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 



 

14 

 

General disorders and administration site conditions 

 Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

 Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

 Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting 

haemostasis (see sections 4.4 and 4.5). 

 

System 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

 

Blood 

and 

lymphatic 

system 

disorders 

Very common: 

Haemorrhage 
α
 

  

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
  

Very common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and 

gastro-intestinal haemorrhage. 

 

Thrombocytopenia and thrombocytosis 

 

Syste

m 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymph

atic 

system 

disord

ers 

Very common: 

Thrombocytosi

s
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 
 

Very common:    

Thrombocytosi

s 
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 

Common:  

Thrombocytosi

s
β
 

Thrombocytop

enia 

Very rare:     

Immuno-

allergic 

thrombocytope

nia 
β
: Platelet increased >400 G/L  

 



 

15 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

Accidental overdose with enoxaparin sodium after IV, extracorporeal or SC administration may lead to 

haemorrhagic complications. Following oral administration of even large doses, it is unlikely that enoxaparin 

sodium will be absorbed. 

 

Management 

The anticoagulant effects can be largely neutralized by the slow IV injection of protamine. The dose of 

protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the anticoagulant 

effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the previous 

8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be administered if 

enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it 

has been determined that a second dose of protamine is required. After 12 hours of the enoxaparin sodium 

injection, protamine administration may not be required. However, even with high doses of protamine, the 

anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 60%) (see the 

prescribing information for protamine salts). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

Pharmacodynamic effects 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
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16 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

 Extended prophylaxis of VTE following orthopaedic surgery  
In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 179 

patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin sodium 

4,000 IU (40 mg) SC, were randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU 

(40 mg) (n=90) once a day SC or to placebo (n=89) for 3 weeks. The incidence of DVT during extended 

prophylaxis was significantly lower for enoxaparin sodium compared to placebo, no PE was reported. No 

major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

once a day SC 

n (%) 

All Treated Extended Prophylaxis 

Patients 
90 (100) 89 (100) 

Total VTE 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)*  18 (20.2) 

 Proximal DVT (%) 5 (5.6)
# 
 7 (8.8) 

*p value versus placebo =0.008 

#p value versus placebo =0.537 

 

 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) SC were randomized to a 

post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n=131) once a day SC or to placebo 

(n=131) for 3 weeks. Similar to the first study the incidence of VTE during extended prophylaxis was 

significantly lower for enoxaparin sodium compared to placebo for both total VTE (enoxaparin sodium 21 

[16%] versus placebo 45 [34.4%]; p=0.001) and proximal DVT (enoxaparin sodium 8 [6.1%] versus placebo 

28 [21.4%]; p=<0.001). No difference in major bleeding was found between the enoxaparin sodium and the 

placebo group. 

 

 Extended prophylaxis of DVT following cancer surgery 
A double-blind, multicenter trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) SC) daily for 6 to 10 days and were 

then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. Bilateral 

venography was performed between days 25 and 31, or sooner if symptoms of venous thromboembolism 

occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis for four weeks after 

surgery for abdominal or pelvic cancer significantly reduced the incidence of venographically demonstrated 

thrombosis, as compared with enoxaparin sodium prophylaxis for one week. The rates of venous 

thromboembolism at the end of the double-blind phase were 12.0 % (n=20) in the placebo group and 4.8% 

(n=8) in the enoxaparin sodium group; p=0.02. This difference persisted at three months [13.8% vs. 5.5% 

(n=23 vs 9), p=0.01]. There were no differences in the rates of bleeding or other complications during the 

double-blind or follow-up periods. 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicenter, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day SC was compared to placebo in the prophylaxis of DVT in medical patients with 

severely restricted mobility during acute illness (defined as walking distance of <10 meters for ≤3 days). 

This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

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17 

 

least one VTE risk factor (age ≥75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day SC, enoxaparin 

sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are provided 

in the table below. 

 

 Enoxaparin 

sodium  

2,000 IU (20 mg) 

once a day SC 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

 

n (%) 

All Treated Medical 

Patients During Acute 

Illness 

287 (100) 291(100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5)  40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 

VTE = Venous thromboembolic events which included DVT, PE, and death considered to 

be thromboembolic in origin 

* p value versus placebo =0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicenter, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day SC, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours SC, or (iii) heparin IV bolus 

(5,000 IU) followed by a continuous infusion (administered to achieve an aPTT of 55 to 85 seconds). A total 

of 900 patients were randomized in the study and all patients were treated. All patients also received warfarin 

sodium (dose adjusted according to prothrombin time to achieve an INR of 2.0 to 3.0), commencing within 

72 hours of initiation of enoxaparin sodium or standard heparin therapy, and continuing for 90 days. 

Enoxaparin sodium or standard heparin therapy was administered for a minimum of 5 days and until the 

targeted warfarin sodium INR was achieved.  Both enoxaparin sodium regimens were equivalent to standard 

heparin therapy in reducing the risk of recurrent venous thromboembolism (DVT and/or PE). The efficacy 

data are provided in the table below. 

 

 Enoxaparin sodium  

150 IU/kg 

(1.5 mg/kg) once a 

day SC 

n (%) 

Enoxaparin sodium  

100 IU/kg 

(1 mg/kg) twice a 

day SC 

n (%) 

Heparin  

aPTT Adjusted IV 

Therapy 

n (%) 

All Treated DVT 

Patients with or 

without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

 DVT Only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

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18 

 

 Proximal DVT 
(%) 

9 (3.0) 6 (1.9) 7 (2.4) 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 

VTE = venous thromboembolic event (DVT and/or PE) 

*The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  
- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicenter study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either SC enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated heparin 

adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 2 days and a maximum of 

8 days, until clinical stabilization, revascularization procedures or hospital discharge. The patients had to be 

followed up to 30 days. In comparison with heparin, enoxaparin sodium significantly reduced the combined 

incidence of angina pectoris, myocardial infarction and death, with a decrease of 19.8 to 16.6% (relative risk 

reduction of 16.2%) on day 14. This reduction in the combined incidence was maintained after 30 days (from 

23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the SC 

injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicenter study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) IV bolus plus a 100 IU/kg 

(1 mg/kg) SC dose followed by an SC injection of 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated 

heparin adjusted based on aPTT for 48 hours. All patients were also treated with  acetylsalicylic acid for a 

minimum of 30 days. The enoxaparin sodium dosing strategy was adjusted for severe renally impaired 

patients and for the elderly of at least 75 years of age. The SC injections of enoxaparin sodium were given 

until hospital discharge or for a maximum of eight days (whichever came first). 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last SC 

administration given less than 8 hours before balloon inflation, IV bolus of 30 IU/ kg (0.3 mg/kg) enoxaparin 

sodium, if the last SC administration given more than 8 hours before balloon inflation. 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p<0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p<0.001). 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p=0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage (a 

measure of net clinical benefit) was significantly lower (p<0.0001) in the enoxaparin sodium group (10.1%) 

as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of treatment 

with enoxaparin sodium. 



 

19 

 

The incidence of major bleeding at 30 days was significantly higher (p<0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated SC administration and after single IV administration. The quantitative determination of anti-Xa 

and anti-IIa pharmacokinetic activities was conducted by validated amidolytic methods. 

 

Absorption 

The absolute bioavailability of enoxaparin sodium after SC injection, based on anti-Xa activity, is close to 

100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after SC injection and achieves 

approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single SC administration of 2,000 IU, 4,000 IU, 

100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 

 

A 3,000 IU (30 mg) IV bolus immediately followed by a 100 IU/kg (1 mg/kg) SC every 12 hours provided 

initial maximum anti-Xa activity level of 1.16 IU/mL (n=16) and average exposure corresponding to 88% of 

steady-state levels. Steady-state is achieved on the second day of treatment. 

 

After repeated SC administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once daily 

regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio about 

15% higher than after a single dose. After repeated SC administration of the 100 IU/kg (1 mg/kg) twice daily 

regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% higher than after a single 

dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 0.52 IU/mL, respectively.  

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated SC administration no accumulation takes 

place. 

 

Plasma anti-IIa activity after SC administration is approximately ten-fold lower than anti-Xa activity. The 

mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following SC injection and 

reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 100 IU/kg (1 mg/kg) twice daily 

and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 

 

Biotransformation 



 

20 

 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour IV infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single SC dose to about 7 hours 

after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal.  However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated SC 

4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine clearance 

<30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated SC 

4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) IV dose however, AUC was two-fold higher than control. 

 

Weight 

After repeated SC 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is marginally 

higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese control 

subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-adjusted 

clearance in obese subjects with SC dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single-SC 4,000 IU (40 mg) dose, 

that anti-Xa exposure is 52% higher in low-weight women (<45 kg) and 27% higher in low-weight men 

(<57 kg) when compared to normal weight control subjects (see section 4.4). 

 

Pharmacokinetic interactions 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week SC toxicity studies both in rats and dogs and at  10 mg/kg/day in the 26-week 

SC and IV toxicity studies both in rats, and monkeys. 



 

21 

 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at SC doses of enoxaparin sodium up to 30 mg/kg/day did not 

reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was found to have no effect 

on fertility or reproductive performance of male and female rats at SC doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Water for injections 

 

6.2 Incompatibilities 
 

SC injection 

Do not mix with other products. 

 

IV (Bolus) Injection (for acute STEMI indication only):  

Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water 

(see section 4.2). 

 

6.3 Shelf life 

 

Pre-filled syringe 

3 years 

 

Diluted medicinal product with sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose 

8 hours 

 

6.4 Special precautions for storage 

 

Store below 25 °C. Do not freeze. 

 

6.5 Nature and contents of container 

 

0.2 mL of solution in: 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 
chlorobutyl rubber stopper and a blue polypropylene plunger rod. The syringe can be additionally 

equipped with needle guard; or 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 

chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe Passive 

needle guard. 

 

Packs of:  

- 1, 2, 6, 10 and 50 pre-filled syringe(s) 
- 2, 6, 10, 20, 50 and 90 pre-filled syringes with needle guard 
- 2 and 6 pre-filled syringes with UltraSafe Passive needle guard 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

INSTRUCTIONS FOR USE: PRE-FILLED SYRINGE  



 

22 

 

 

How to give yourself an injection of Inhixa 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 



 

23 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has a needle guard attached to it in order to protect you from needle stick injury. 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 



 

24 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Push hard the plunger. The needle guard, which is in the form of a plastic cylinder, will be activated 

automatically and it will completely cover the needle. 

 

 

 

 

 

 



 

25 

 

 

10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has UltraSafe Passive needle guard attached to it in order to protect you from needle 

stick injury.  

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 



 

26 

 

 

Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
 

To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Let go of the plunger and allow the syringe to move up until the entire needle is guarded and locks 

into place. 

 
 

10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 
 



 

27 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/001 

EU/1/16/1132/002 

EU/1/16/1132/011 

EU/1/16/1132/012 

EU/1/16/1132/021 

EU/1/16/1132/023 

EU/1/16/1132/033 

EU/1/16/1132/034 

EU/1/16/1132/051 

EU/1/16/1132/053 

EU/1/16/1132/054 

EU/1/16/1132/064 

EU/1/16/1132/065 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

 

 

 

  

http://www.ema.europa.eu/


 

28 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 4,000 IU (40 mg)/0.4 mL solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

10,000 IU/mL (100 mg/mL) solution for injection 

 

Each pre-filled syringe contains enoxaparin sodium 4,000 IU anti-Xa activity (equivalent to 40 mg) in 

0.4 mL water for injections. 

 

For the full list of excipients, see section 6.1. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerization of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in pre-filled syringe. 

Clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in particular 
those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility at 

increased risk of venous thromboembolism.  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to require 
thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), in 

combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to be 
managed medically or with subsequent percutaneous coronary intervention (PCI). 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 



 

29 

 

 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous (SC) injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk surgery.  

In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 7-

10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the patient no 

longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by SC injection preferably started 12 hours before surgery. If there is a need for 

earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high risk patient 

waiting for a deferred orthopaedic surgery), the last injection should be administered no later than 

12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis 
up to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal 
or pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by SC injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status (e.g. 

mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered SC either as a once daily injection of 150 IU/kg (1.5 mg/kg) or as 

twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by SC injection administered in combination with antiplatelet 

therapy. Treatment should be maintained for a minimum of 2 days and continued until clinical 

stabilization. The usual duration of treatment is 2 to 8 days.  

Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading 

dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75–325 mg/day 

long-term regardless of treatment strategy. 



 

30 

 

 

 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous (IV) 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) SC dose followed by 100 IU/kg (1 mg/kg) 

administered SC every 12 hours (maximum 10,000 IU (100 mg) for each of the first two SC doses). 

Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg to 325 mg once daily) should be 

administered concomitantly unless contraindicated. The recommended duration of treatment is 8 days or 

until hospital discharge, whichever comes first. When administered in conjunction with a thrombolytic 

(fibrin specific or non-fibrin specific), enoxaparin sodium should be given between 15 minutes before 

and 30 minutes after the start of fibrinolytic therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last dose of enoxaparin sodium SC was given less than 

8 hours before balloon inflation, no additional dosing is needed. If the last SC administration 

was given more than 8 hours before balloon inflation, an IV bolus of 30 IU/kg (0.3 mg/kg) 

enoxaparin sodium should be administered. 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established. 

 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below “renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥75 years of age, an initial IV bolus must not be used. 

Initiate dosing with 75 IU/kg (0.75 mg/kg) SC every 12 hours (maximum 7,500 IU (75 mg) for each of the 

first two SC doses only, followed by 75 IU/kg (0.75 mg/kg) SC dosing for the remaining doses). For dosage 

in elderly patients with impaired kidney function, see below “renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

 Severe renal impairment  
Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease  

 

2,000 IU (20 mg) SC once daily 

Treatment of  DVT and PE 100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of acute STEMI (patients under 75) 

 

 

 

Treatment of acute STEMI (patients over 75) 

1 x 3,000 IU (30 mg) IV bolus plus 100 IU/kg 

(1 mg/kg) body weight SC and then 100 IU/kg 

(1 mg/kg) body weight SC every 24 hours 

 

No IV initial bolus, 100 IU/kg (1 mg/kg) body 

weight SC and then 100 IU/kg (1 mg/kg) body 

weight SC every 24 hours 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

 Moderate and mild renal impairment 



 

31 

 

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30-

50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring is 

advised. 

 

Method of administration  

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thrombo-embolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by SC injection. 

 For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a 
SC injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The pre-filled disposable syringe is ready for immediate use.  

 

The use of a tuberculin syringe or equivalent is recommended when using ampoules or multiple-dose vials to 

assure withdrawal of the appropriate volume of drug. 

 

 SC injection technique: 
Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep SC injection.  

 

Do not expel the air bubble from the syringe before the injection to avoid the loss of drug when using pre-

filled syringes. When the quantity of drug to be injected requires to be adjusted based on the patient’s body 

weight, use the graduated pre-filled syringes to reach the required volume by discarding the excess before 

injection. Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations 

on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. Do not rub the 

injection site after administration. 

 

Note for the pre-filled syringes fitted with an automatic safety system: The safety system is triggered at the 

end of the injection (see instructions in section 6.6). 

 

In case of self-administration, patient should be advised to follow instructions provided in the patient 

information leaflet included in the pack of this medicine. 

 

 IV (bolus) injection (for acute STEMI indication only): 
For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a SC 

injection.  

For IV injection, either the multidose vial or pre-filled syringe can be used. 

Enoxaparin sodium should be administered through an IV line. It should not be mixed or co-administered 

with other medications. To avoid the possible mixture of enoxaparin sodium with other drugs, the IV access 

chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the IV 

bolus administration of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely 

administered with normal saline solution (0.9%) or 5% dextrose in water. 

 

o Initial 3,000 IU (30 mg) bolus 



 

32 

 

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the IV line. 

 

o Additional bolus for PCI when last SC administration was given more than 8 hours before balloon 
inflation 

For patients being managed with PCI, an additional IV bolus of 30 IU/kg (0.3 mg/kg) is to be administered if 

last SC administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either normal saline solution (0.9%) or 5% 

dextrose in water) as follows:  

Withdraw 30 mL from the infusion bag with a syringe and discard the liquid. Inject the complete contents of 

the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe into the 20 mL remaining in the bag. Gently mix 

the contents of the bag. Withdraw the required volume of diluted solution with a syringe for administration 

into the IV line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 



 

33 

 

Volume to be injected through IV line after dilution is completed at a concentration of 300 IU (3 mg) /mL. 

 

Weight 

 

Required dose 

 30 IU/kg (0.3 mg/kg) 

Volume to inject when 

diluted to a final 

concentration of  

 300 IU (3 mg) / mL 

 

[kg] 

 

IU 

 

[mg] 

 

[mL] 

 

45 

 

1350 

 

13.5 

 

4.5 

50 1500 15 5 

55 1650 16.5 5.5 

60 1800 18 6 

65 1950 19.5 6.5 

70 2100 21 7 

75 2250 22.5 7.5 

80 2400 24 8 

85 2550 25.5 8.5 

90 2700 27 9 

95 2850 28.5 9.5 

100 3000 30 10 

105 3150 31.5 10.5 

110 3300 33 11 

115 3450 34.5 11.5 

120 3600 36 12 

125 3750 37.5 12.5 

130 3900 39 13 

135 4050 40.5 13.5 

140 4200 42 14 

145 4350 43.5 14.5 

150 4500 45 15 

  

 

 Arterial line injection: 
It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 

Switch between enoxaparin sodium and oral anticoagulants 

 Switch between enoxaparin sodium and vitamin K antagonists (VKA)  
Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalized 

Ratio (INR)] must be intensified to monitor the effect of VKA. 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

 Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 
For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 



 

34 

 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

- At doses used for prophylaxis 
A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin 

sodium at prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing 

the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with 

neuraxial anaesthesia. 

- At doses used for treatment 
A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin 

sodium at curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg 

(1 mg/kg) twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay 

before catheter placement or removal.  

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH) or to any of the excipients listed in section 6.1; 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

 

4.4 Special warnings and precautions for use 
 

 General 
Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

 History of HIT (>100 days) 



 

35 

 

Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-

induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such a 

case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments 

are considered (e.g. danaparoid sodium or lepirudin). 

 

 Monitoring of platelet counts 
The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 

 

 Haemorrhage 
As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 
- neuro- or ophthalmologic surgery, 
- concomitant use of medications affecting haemostasis (see section 4.5). 

 

 Laboratory tests 
At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

 Spinal/Epidural anaesthesia or lumbar puncture 
Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 



 

36 

 

To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach a 

sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance [15--

30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is more 

prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

 Skin necrosis / cutaneous vasculitis 
Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

 Percutaneous coronary revascularization procedures 
To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If the treatment with 

enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours 

after sheath removal. The site of the procedure should be observed for signs of bleeding or hematoma 

formation. 

 

 Acute infective endocarditis 
Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after a 

careful individual benefit risk assessment. 

 

 Mechanical prosthetic heart valves 
The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 

 Pregnant women with mechanical prosthetic heart valves 
The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg ) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

 Elderly 
No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 



 

37 

 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

 Renal impairment 
In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which increases the 

risk of bleeding. In these patients, careful clinical monitoring is advised, and biological monitoring by anti-

Xa activity measurement might be considered (see sections 4.2 and 5.2). 

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 

 Hepatic impairment 
Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

 Low weight 
An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

 Obese Patients 
Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI >30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 

 

 Hyperkalaemia 
Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  

 Traceability 
LMWHs are biological medicinal products. In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded.  

 

Sodium content 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended:  

 Medicinal products affecting haemostasis (see section 4.4) 
It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 



 

38 

 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 

 

Concomitant use with caution: 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

 Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  

- Systemic glucocorticoids. 
 

 Medicinal products increasing potassium levels: 
Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 

Breast-feeding  

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely.  Inhixa can be used during breastfeeding. 

 

Fertility 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 



 

39 

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) SC once daily for prophylaxis of deep vein thrombosis 

following surgery or in acutely ill medical patients with severely restricted mobility. In treatment of DVT 

with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg (1 mg/kg) SC 

dose every 12 hours or a 150 IU/kg (1.5 mg/kg) SC dose once a day. In the clinical studies for treatment of 

unstable angina and non-Q-wave myocardial infarction, doses were 100 IU/kg (1 mg/kg) SC every 12 hours, 

and in the clinical study for treatment of acute STEMI enoxaparin sodium regimen was a 3,000 IU (30 mg) 

IV bolus followed by 100 IU/kg (1 mg/kg) SC every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see section 4.4 and 'Description of selected adverse reactions' below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 

1/1000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

 Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 

 Rare: Eosinophilia* 

 Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 
complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

 Common: Allergic reaction 

 Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

 Common: Headache* 
 

Vascular disorders 

 Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees of 
neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 

 Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of normality) 

 Uncommon: Hepatocellular liver injury *  

 Rare: Cholestatic liver injury* 
 

Skin and subcutaneous tissue disorders 

 Common: Urticaria, pruritus, erythema  

 Uncommon: Bullous dermatitis 

 Rare: Alopecia* 

 Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena have 
been usually preceded by purpura or erythematous plaques, infiltrated and painful). 

Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 

resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

 Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 



 

40 

 

General disorders and administration site conditions 

 Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

 Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

 Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting 

haemostasis (see sections 4.4 and 4.5). 

 

System 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

 

Blood 

and 

lymphatic 

system 

disorders 

Very common: 

Haemorrhage 
α
 

  

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
  

Very common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and 

gastro-intestinal haemorrhage. 

 

Thrombocytopenia and thrombocytosis 

 

Syste

m 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymph

atic 

system 

disord

ers 

Very common: 

Thrombocytosi

s
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 
 

Very common:    

Thrombocytosi

s 
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 

Common:  

Thrombocytosi

s
β
 

Thrombocytop

enia 

Very rare:     

Immuno-

allergic 

thrombocytope

nia 
β
: Platelet increased >400 G/L  

 



 

41 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

Accidental overdose with enoxaparin sodium after IV, extracorporeal or SC administration may lead to 

haemorrhagic complications. Following oral administration of even large doses, it is unlikely that enoxaparin 

sodium will be absorbed. 

 

Management 

The anticoagulant effects can be largely neutralized by the slow IV injection of protamine. The dose of 

protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the anticoagulant 

effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the previous 

8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be administered if 

enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it 

has been determined that a second dose of protamine is required. After 12 hours of the enoxaparin sodium 

injection, protamine administration may not be required. However, even with high doses of protamine, the 

anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 60%) (see the 

prescribing information for protamine salts). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

Pharmacodynamic effects 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/


 

42 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

 Extended prophylaxis of VTE following orthopaedic surgery  
In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 179 

patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin sodium 

4,000 IU (40 mg) SC, were randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU 

(40 mg) (n=90) once a day SC or to placebo (n=89) for 3 weeks. The incidence of DVT during extended 

prophylaxis was significantly lower for enoxaparin sodium compared to placebo, no PE was reported. No 

major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

once a day SC 

n (%) 

All Treated Extended Prophylaxis 

Patients 
90 (100) 89 (100) 

Total VTE 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)*  18 (20.2) 

 Proximal DVT (%) 5 (5.6)
# 
 7 (8.8) 

*p value versus placebo =0.008 

#p value versus placebo =0.537 

 

 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) SC were randomized to a 

post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n=131) once a day SC or to placebo 

(n=131) for 3 weeks. Similar to the first study the incidence of VTE during extended prophylaxis was 

significantly lower for enoxaparin sodium compared to placebo for both total VTE (enoxaparin sodium 21 

[16%] versus placebo 45 [34.4%]; p=0.001) and proximal DVT (enoxaparin sodium 8 [6.1%] versus placebo 

28 [21.4%]; p=<0.001). No difference in major bleeding was found between the enoxaparin sodium and the 

placebo group. 

 

 Extended prophylaxis of DVT following cancer surgery 
A double-blind, multicenter trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) SC) daily for 6 to 10 days and were 

then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. Bilateral 

venography was performed between days 25 and 31, or sooner if symptoms of venous thromboembolism 

occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis for four weeks after 

surgery for abdominal or pelvic cancer significantly reduced the incidence of venographically demonstrated 

thrombosis, as compared with enoxaparin sodium prophylaxis for one week. The rates of venous 

thromboembolism at the end of the double-blind phase were 12.0 % (n=20) in the placebo group and 4.8% 

(n=8) in the enoxaparin sodium group; p=0.02. This difference persisted at three months [13.8% vs. 5.5% 

(n=23 vs 9), p=0.01]. There were no differences in the rates of bleeding or other complications during the 

double-blind or follow-up periods. 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicenter, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day SC was compared to placebo in the prophylaxis of DVT in medical patients with 

severely restricted mobility during acute illness (defined as walking distance of <10 meters for ≤3 days). 

This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&audience=consumer#footnote-32


 

43 

 

least one VTE risk factor (age ≥75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day SC, enoxaparin 

sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are provided 

in the table below. 

 

 Enoxaparin 

sodium  

2,000 IU (20 mg) 

once a day SC 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

 

n (%) 

All Treated Medical 

Patients During Acute 

Illness 

287 (100) 291(100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5)  40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 

VTE = Venous thromboembolic events which included DVT, PE, and death considered to 

be thromboembolic in origin 

* p value versus placebo =0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicenter, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day SC, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours SC, or (iii) heparin IV bolus 

(5,000 IU) followed by a continuous infusion (administered to achieve an aPTT of 55 to 85 seconds). A total 

of 900 patients were randomized in the study and all patients were treated. All patients also received warfarin 

sodium (dose adjusted according to prothrombin time to achieve an INR of 2.0 to 3.0), commencing within 

72 hours of initiation of enoxaparin sodium or standard heparin therapy, and continuing for 90 days. 

Enoxaparin sodium or standard heparin therapy was administered for a minimum of 5 days and until the 

targeted warfarin sodium INR was achieved.  Both enoxaparin sodium regimens were equivalent to standard 

heparin therapy in reducing the risk of recurrent venous thromboembolism (DVT and/or PE). The efficacy 

data are provided in the table below. 

 

 Enoxaparin sodium  

150 IU/kg 

(1.5 mg/kg) once a 

day SC 

n (%) 

Enoxaparin sodium  

100 IU/kg 

(1 mg/kg) twice a 

day SC 

n (%) 

Heparin  

aPTT Adjusted IV 

Therapy 

n (%) 

All Treated DVT 

Patients with or 

without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

 DVT Only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&audience=consumer#footnote-40


 

44 

 

 Proximal DVT 
(%) 

9 (3.0) 6 (1.9) 7 (2.4) 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 

VTE = venous thromboembolic event (DVT and/or PE) 

*The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  
- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicenter study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either SC enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated heparin 

adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 2 days and a maximum of 

8 days, until clinical stabilization, revascularization procedures or hospital discharge. The patients had to be 

followed up to 30 days. In comparison with heparin, enoxaparin sodium significantly reduced the combined 

incidence of angina pectoris, myocardial infarction and death, with a decrease of 19.8 to 16.6% (relative risk 

reduction of 16.2%) on day 14. This reduction in the combined incidence was maintained after 30 days (from 

23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the SC 

injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicenter study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) IV bolus plus a 100 IU/kg 

(1 mg/kg) SC dose followed by an SC injection of 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated 

heparin adjusted based on aPTT for 48 hours. All patients were also treated with  acetylsalicylic acid for a 

minimum of 30 days. The enoxaparin sodium dosing strategy was adjusted for severe renally impaired 

patients and for the elderly of at least 75 years of age. The SC injections of enoxaparin sodium were given 

until hospital discharge or for a maximum of eight days (whichever came first). 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last SC 

administration given less than 8 hours before balloon inflation, IV bolus of 30 IU/ kg (0.3 mg/kg) enoxaparin 

sodium, if the last SC administration given more than 8 hours before balloon inflation. 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p<0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p<0.001). 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p=0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage (a 

measure of net clinical benefit) was significantly lower (p<0.0001) in the enoxaparin sodium group (10.1%) 

as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of treatment 

with enoxaparin sodium. 



 

45 

 

The incidence of major bleeding at 30 days was significantly higher (p<0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated SC administration and after single IV administration. The quantitative determination of anti-Xa 

and anti-IIa pharmacokinetic activities was conducted by validated amidolytic methods. 

 

Absorption 

The absolute bioavailability of enoxaparin sodium after SC injection, based on anti-Xa activity, is close to 

100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after SC injection and achieves 

approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single SC administration of 2,000 IU, 4,000 IU, 

100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 

 

A 3,000 IU (30 mg) IV bolus immediately followed by a 100 IU/kg (1 mg/kg) SC every 12 hours provided 

initial maximum anti-Xa activity level of 1.16 IU/mL (n=16) and average exposure corresponding to 88% of 

steady-state levels. Steady-state is achieved on the second day of treatment. 

 

After repeated SC administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once daily 

regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio about 

15% higher than after a single dose. After repeated SC administration of the 100 IU/kg (1 mg/kg) twice daily 

regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% higher than after a single 

dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 0.52 IU/mL, respectively.  

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated SC administration no accumulation takes 

place. 

 

Plasma anti-IIa activity after SC administration is approximately ten-fold lower than anti-Xa activity. The 

mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following SC injection and 

reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 100 IU/kg (1 mg/kg) twice daily 

and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 

 



 

46 

 

Biotransformation 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour IV infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single SC dose to about 7 hours 

after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal.  However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated SC 

4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine clearance 

<30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated SC 

4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) IV dose however, AUC was two-fold higher than control. 

 

Weight 

After repeated SC 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is marginally 

higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese control 

subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-adjusted 

clearance in obese subjects with SC dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single-SC 4,000 IU (40 mg) dose, 

that anti-Xa exposure is 52% higher in low-weight women (<45 kg) and 27% higher in low-weight men 

(<57 kg) when compared to normal weight control subjects (see section 4.4). 

 

 

Pharmacokinetic interactions 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 



 

47 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week SC toxicity studies both in rats and dogs and at  10 mg/kg/day in the 26-week 

SC and IV toxicity studies both in rats, and monkeys. 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at SC doses of enoxaparin sodium up to 30 mg/kg/day did not 

reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was found to have no effect 

on fertility or reproductive performance of male and female rats at SC doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Water for injections 

 

6.2 Incompatibilities 
 

SC injection 

Do not mix with other products. 

 

IV (Bolus) Injection (for acute STEMI indication only):  

Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water 

(see section 4.2). 

 

6.3 Shelf life 

 

Pre-filled syringe 

3 years 

 

Diluted medicinal product with sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose 

8 hours 

 

6.4 Special precautions for storage 

 

Store below 25 °C. Do not freeze. 

 

6.5 Nature and contents of container 

 

0.4 mL of solution in: 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 
chlorobutyl rubber stopper and a yellow polypropylene plunger rod. The syringe can be additionally 

equipped with needle guard; or 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 

chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe Passive 

needle guard. 

 

Packs of:  

- 2, 5, 6, 10, 30 and 50 pre-filled syringes 
- 2, 5, 6, 10, 20, 30, 50 and 90 pre-filled syringes with needle guard 
- 2 and 6 pre-filled syringes with UltraSafe Passive needle guard 

 



 

48 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

INSTRUCTIONS FOR USE: PRE-FILLED SYRINGE  

 

How to give yourself an injection of Inhixa 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 



 

49 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has a needle guard attached to it in order to protect you from needle stick injury. 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 



 

50 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Push hard the plunger. The needle guard, which is in the form of a plastic cylinder, will be activated 

automatically and it will completely cover the needle. 



 

51 

 

 
10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has UltraSafe Passive needle guard attached to it in order to protect you from needle 

stick injury.  

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
 



 

52 

 

Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
 

To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Let go of the plunger and allow the syringe to move up until the entire needle is guarded and locks 

into place. 

 
 

10)  Drop the used syringe the sharps container. Close the container lid tightly and place the container out 

of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 
Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 



 

53 

 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/003 

EU/1/16/1132/004 

EU/1/16/1132/013 

EU/1/16/1132/014 

EU/1/16/1132/024 

EU/1/16/1132/025 

EU/1/16/1132/035 

EU/1/16/1132/036 

EU/1/16/1132/043 

EU/1/16/1132/044 

EU/1/16/1132/052 

EU/1/16/1132/055 

EU/1/16/1132/056 

EU/1/16/1132/066 

EU/1/16/1132/067 

EU/1/16/1132/068 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

  

http://www.ema.europa.eu/


 

54 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 6,000 IU (60 mg)/0.6 mL solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

10,000 IU/mL (100 mg/mL) solution for injection 

 

Each pre-filled syringe contains enoxaparin sodium 6,000 IU anti-Xa activity (equivalent to 60 mg) in 0.6 

mL water for injections. 

 

For the full list of excipients, see section 6.1. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerization of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in pre-filled syringe. 

Clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in particular 
those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility at 

increased risk of venous thromboembolism.  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to require 
thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), in 

combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to be 
managed medically or with subsequent percutaneous coronary intervention (PCI). 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 



 

55 

 

 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous (SC) injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk surgery.  

In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 7-

10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the patient no 

longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by SC injection preferably started 12 hours before surgery. If there is a need for 

earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high risk patient 

waiting for a deferred orthopaedic surgery), the last injection should be administered no later than 

12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis 
up to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal 
or pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by SC injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status (e.g. 

mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered SC either as a once daily injection of 150 IU/kg (1.5 mg/kg) or as 

twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by SC injection administered in combination with antiplatelet 

therapy. Treatment should be maintained for a minimum of 2 days and continued until clinical 

stabilization. The usual duration of treatment is 2 to 8 days.  

Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading 

dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75–325 mg/day 

long-term regardless of treatment strategy. 



 

56 

 

 

 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous (IV) 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) SC dose followed by 100 IU/kg (1 mg/kg) 

administered SC every 12 hours (maximum 10,000 IU (100 mg) for each of the first two SC doses). 

Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg to 325 mg once daily) should be 

administered concomitantly unless contraindicated. The recommended duration of treatment is 8 days or 

until hospital discharge, whichever comes first. When administered in conjunction with a thrombolytic 

(fibrin specific or non-fibrin specific), enoxaparin sodium should be given between 15 minutes before 

and 30 minutes after the start of fibrinolytic therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last dose of enoxaparin sodium SC was given less than 

8 hours before balloon inflation, no additional dosing is needed. If the last SC administration 

was given more than 8 hours before balloon inflation, an IV bolus of 30 IU/kg (0.3 mg/kg) 

enoxaparin sodium should be administered. 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established. 

 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below “renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥75 years of age, an initial IV bolus must not be used. 

Initiate dosing with 75 IU/kg (0.75 mg/kg) SC every 12 hours (maximum 7,500 IU (75 mg) for each of the 

first two SC doses only, followed by 75 IU/kg (0.75 mg/kg) SC dosing for the remaining doses). For dosage 

in elderly patients with impaired kidney function, see below “renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

 Severe renal impairment  
Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease  

 

2,000 IU (20 mg) SC once daily 

Treatment of  DVT and PE 100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of acute STEMI (patients under 75) 

 

 

 

Treatment of acute STEMI (patients over 75) 

1 x 3,000 IU (30 mg) IV bolus plus 100 IU/kg 

(1 mg/kg) body weight SC and then 100 IU/kg 

(1 mg/kg) body weight SC every 24 hours 

 

No IV initial bolus, 100 IU/kg (1 mg/kg) body 

weight SC and then 100 IU/kg (1 mg/kg) body 

weight SC every 24 hours 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

 Moderate and mild renal impairment 



 

57 

 

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30-

50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring is 

advised. 

 

Method of administration  

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thrombo-embolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by SC injection. 

 For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a 
SC injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The pre-filled disposable syringe is ready for immediate use.  

 

The use of a tuberculin syringe or equivalent is recommended when using ampoules or multiple-dose vials to 

assure withdrawal of the appropriate volume of drug. 

 

 SC injection technique: 
Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep SC injection.  

 

Do not expel the air bubble from the syringe before the injection to avoid the loss of drug when using pre-

filled syringes. When the quantity of drug to be injected requires to be adjusted based on the patient’s body 

weight, use the graduated pre-filled syringes to reach the required volume by discarding the excess before 

injection. Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations 

on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. Do not rub the 

injection site after administration. 

 

Note for the pre-filled syringes fitted with an automatic safety system: The safety system is triggered at the 

end of the injection (see instructions in section 6.6). 

 

In case of self-administration, patient should be advised to follow instructions provided in the patient 

information leaflet included in the pack of this medicine. 

 

 IV (bolus) injection (for acute STEMI indication only): 
For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a SC 

injection.  

For IV injection, either the multidose vial or pre-filled syringe can be used. 

Enoxaparin sodium should be administered through an IV line. It should not be mixed or co-administered 

with other medications. To avoid the possible mixture of enoxaparin sodium with other drugs, the IV access 

chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the IV 

bolus administration of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely 

administered with normal saline solution (0.9%) or 5% dextrose in water. 

 

o Initial 3,000 IU (30 mg) bolus 



 

58 

 

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the IV line. 

 

o Additional bolus for PCI when last SC administration was given more than 8 hours before balloon 
inflation 

For patients being managed with PCI, an additional IV bolus of 30 IU/kg (0.3 mg/kg) is to be administered if 

last SC administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either normal saline solution (0.9%) or 5% 

dextrose in water) as follows:  

Withdraw 30 mL from the infusion bag with a syringe and discard the liquid. Inject the complete contents of 

the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe into the 20 mL remaining in the bag. Gently mix 

the contents of the bag. Withdraw the required volume of diluted solution with a syringe for administration 

into the IV line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 



 

59 

 

Volume to be injected through IV line after dilution is completed at a concentration of 300 IU (3 mg) /mL. 

 

Weight 

 

Required dose 

 30 IU/kg (0.3 mg/kg) 

Volume to inject when 

diluted to a final 

concentration of  

 300 IU (3 mg) / mL 

 

[kg] 

 

IU 

 

[mg] 

 

[mL] 

 

45 

 

1350 

 

13.5 

 

4.5 

50 1500 15 5 

55 1650 16.5 5.5 

60 1800 18 6 

65 1950 19.5 6.5 

70 2100 21 7 

75 2250 22.5 7.5 

80 2400 24 8 

85 2550 25.5 8.5 

90 2700 27 9 

95 2850 28.5 9.5 

100 3000 30 10 

105 3150 31.5 10.5 

110 3300 33 11 

115 3450 34.5 11.5 

120 3600 36 12 

125 3750 37.5 12.5 

130 3900 39 13 

135 4050 40.5 13.5 

140 4200 42 14 

145 4350 43.5 14.5 

150 4500 45 15 

  

 

 Arterial line injection: 
It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 

Switch between enoxaparin sodium and oral anticoagulants 

 Switch between enoxaparin sodium and vitamin K antagonists (VKA)  
Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalized 

Ratio (INR)] must be intensified to monitor the effect of VKA. 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

 Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 
For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 



 

60 

 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

- At doses used for prophylaxis 
A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin 

sodium at prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing 

the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with 

neuraxial anaesthesia. 

- At doses used for treatment 
A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin 

sodium at curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg 

(1 mg/kg) twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay 

before catheter placement or removal.  

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH) or to any of the excipients listed in section 6.1; 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

 

4.4 Special warnings and precautions for use 
 

 General 
Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

 History of HIT (>100 days) 



 

61 

 

Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-

induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such a 

case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments 

are considered (e.g. danaparoid sodium or lepirudin). 

 

 Monitoring of platelet counts 
The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 

 

 Haemorrhage 
As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 
- neuro- or ophthalmologic surgery, 
- concomitant use of medications affecting haemostasis (see section 4.5). 

 

 Laboratory tests 
At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

 Spinal/Epidural anaesthesia or lumbar puncture 
Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 



 

62 

 

To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach a 

sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance [15--

30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is more 

prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

 Skin necrosis / cutaneous vasculitis 
Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

 Percutaneous coronary revascularization procedures 
To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If the treatment with 

enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours 

after sheath removal. The site of the procedure should be observed for signs of bleeding or hematoma 

formation. 

 

 Acute infective endocarditis 
Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after a 

careful individual benefit risk assessment. 

 

 Mechanical prosthetic heart valves 
The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 

 Pregnant women with mechanical prosthetic heart valves 
The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg ) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

 Elderly 
No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 



 

63 

 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

 Renal impairment 
In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which increases the 

risk of bleeding. In these patients, careful clinical monitoring is advised, and biological monitoring by anti-

Xa activity measurement might be considered (see sections 4.2 and 5.2). 

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 

 Hepatic impairment 
Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

 Low weight 
An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

 Obese Patients 
Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI >30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 

 

 Hyperkalaemia 
Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  

 Traceability 
LMWHs are biological medicinal products. In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded. 

  

Sodium content 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended:  

 Medicinal products affecting haemostasis (see section 4.4) 
It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 



 

64 

 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 

 

Concomitant use with caution: 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

 Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  

- Systemic glucocorticoids. 
 

 Medicinal products increasing potassium levels: 
Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 

Breast-feeding  

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely.  Inhixa can be used during breastfeeding. 

 

Fertility 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 



 

65 

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) SC once daily for prophylaxis of deep vein thrombosis 

following surgery or in acutely ill medical patients with severely restricted mobility. In treatment of DVT 

with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg (1 mg/kg) SC 

dose every 12 hours or a 150 IU/kg (1.5 mg/kg) SC dose once a day. In the clinical studies for treatment of 

unstable angina and non-Q-wave myocardial infarction, doses were 100 IU/kg (1 mg/kg) SC every 12 hours, 

and in the clinical study for treatment of acute STEMI enoxaparin sodium regimen was a 3,000 IU (30 mg) 

IV bolus followed by 100 IU/kg (1 mg/kg) SC every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see section 4.4 and 'Description of selected adverse reactions' below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 

1/1000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

 Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 

 Rare: Eosinophilia* 

 Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 
complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

 Common: Allergic reaction 

 Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

 Common: Headache* 
 

Vascular disorders 

 Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees of 
neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 

 Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of normality) 

 Uncommon: Hepatocellular liver injury *  

 Rare: Cholestatic liver injury* 
 

Skin and subcutaneous tissue disorders 

 Common: Urticaria, pruritus, erythema  

 Uncommon: Bullous dermatitis 

 Rare: Alopecia* 

 Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena have 
been usually preceded by purpura or erythematous plaques, infiltrated and painful). 

Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 

resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

 Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 



 

66 

 

General disorders and administration site conditions 

 Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

 Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

 Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting 

haemostasis (see sections 4.4 and 4.5). 

 

System 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

 

Blood 

and 

lymphatic 

system 

disorders 

Very common: 

Haemorrhage 
α
 

  

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
  

Very common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and 

gastro-intestinal haemorrhage. 

 

Thrombocytopenia and thrombocytosis 

 

Syste

m 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymph

atic 

system 

disord

ers 

Very common: 

Thrombocytosi

s
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 
 

Very common:    

Thrombocytosi

s 
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 

Common:  

Thrombocytosi

s
β
 

Thrombocytop

enia 

Very rare:     

Immuno-

allergic 

thrombocytope

nia 
β
: Platelet increased >400 G/L  

 



 

67 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

Accidental overdose with enoxaparin sodium after IV, extracorporeal or SC administration may lead to 

haemorrhagic complications. Following oral administration of even large doses, it is unlikely that enoxaparin 

sodium will be absorbed. 

 

Management 

The anticoagulant effects can be largely neutralized by the slow IV injection of protamine. The dose of 

protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the anticoagulant 

effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the previous 

8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be administered if 

enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it 

has been determined that a second dose of protamine is required. After 12 hours of the enoxaparin sodium 

injection, protamine administration may not be required. However, even with high doses of protamine, the 

anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 60%) (see the 

prescribing information for protamine salts). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

Pharmacodynamic effects 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

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68 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

 Extended prophylaxis of VTE following orthopaedic surgery  
In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 179 

patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin sodium 

4,000 IU (40 mg) SC, were randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU 

(40 mg) (n=90) once a day SC or to placebo (n=89) for 3 weeks. The incidence of DVT during extended 

prophylaxis was significantly lower for enoxaparin sodium compared to placebo, no PE was reported. No 

major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

once a day SC 

n (%) 

All Treated Extended Prophylaxis 

Patients 
90 (100) 89 (100) 

Total VTE 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)*  18 (20.2) 

 Proximal DVT (%) 5 (5.6)
# 
 7 (8.8) 

*p value versus placebo =0.008 

#p value versus placebo =0.537 

 

 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) SC were randomized to a 

post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n=131) once a day SC or to placebo 

(n=131) for 3 weeks. Similar to the first study the incidence of VTE during extended prophylaxis was 

significantly lower for enoxaparin sodium compared to placebo for both total VTE (enoxaparin sodium 21 

[16%] versus placebo 45 [34.4%]; p=0.001) and proximal DVT (enoxaparin sodium 8 [6.1%] versus placebo 

28 [21.4%]; p=<0.001). No difference in major bleeding was found between the enoxaparin sodium and the 

placebo group. 

 

 Extended prophylaxis of DVT following cancer surgery 
A double-blind, multicenter trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) SC) daily for 6 to 10 days and were 

then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. Bilateral 

venography was performed between days 25 and 31, or sooner if symptoms of venous thromboembolism 

occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis for four weeks after 

surgery for abdominal or pelvic cancer significantly reduced the incidence of venographically demonstrated 

thrombosis, as compared with enoxaparin sodium prophylaxis for one week. The rates of venous 

thromboembolism at the end of the double-blind phase were 12.0 % (n=20) in the placebo group and 4.8% 

(n=8) in the enoxaparin sodium group; p=0.02. This difference persisted at three months [13.8% vs. 5.5% 

(n=23 vs 9), p=0.01]. There were no differences in the rates of bleeding or other complications during the 

double-blind or follow-up periods. 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicenter, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day SC was compared to placebo in the prophylaxis of DVT in medical patients with 

severely restricted mobility during acute illness (defined as walking distance of <10 meters for ≤3 days). 

This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

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69 

 

least one VTE risk factor (age ≥75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day SC, enoxaparin 

sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are provided 

in the table below. 

 

 Enoxaparin 

sodium  

2,000 IU (20 mg) 

once a day SC 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

 

n (%) 

All Treated Medical 

Patients During Acute 

Illness 

287 (100) 291(100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5)  40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 

VTE = Venous thromboembolic events which included DVT, PE, and death considered to 

be thromboembolic in origin 

* p value versus placebo =0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicenter, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day SC, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours SC, or (iii) heparin IV bolus 

(5,000 IU) followed by a continuous infusion (administered to achieve an aPTT of 55 to 85 seconds). A total 

of 900 patients were randomized in the study and all patients were treated. All patients also received warfarin 

sodium (dose adjusted according to prothrombin time to achieve an INR of 2.0 to 3.0), commencing within 

72 hours of initiation of enoxaparin sodium or standard heparin therapy, and continuing for 90 days. 

Enoxaparin sodium or standard heparin therapy was administered for a minimum of 5 days and until the 

targeted warfarin sodium INR was achieved.  Both enoxaparin sodium regimens were equivalent to standard 

heparin therapy in reducing the risk of recurrent venous thromboembolism (DVT and/or PE). The efficacy 

data are provided in the table below. 

 

 Enoxaparin sodium  

150 IU/kg 

(1.5 mg/kg) once a 

day SC 

n (%) 

Enoxaparin sodium  

100 IU/kg 

(1 mg/kg) twice a 

day SC 

n (%) 

Heparin  

aPTT Adjusted IV 

Therapy 

n (%) 

All Treated DVT 

Patients with or 

without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

 DVT Only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

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70 

 

 Proximal DVT 
(%) 

9 (3.0) 6 (1.9) 7 (2.4) 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 

VTE = venous thromboembolic event (DVT and/or PE) 

*The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  
- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicenter study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either SC enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated heparin 

adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 2 days and a maximum of 

8 days, until clinical stabilization, revascularization procedures or hospital discharge. The patients had to be 

followed up to 30 days. In comparison with heparin, enoxaparin sodium significantly reduced the combined 

incidence of angina pectoris, myocardial infarction and death, with a decrease of 19.8 to 16.6% (relative risk 

reduction of 16.2%) on day 14. This reduction in the combined incidence was maintained after 30 days (from 

23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the SC 

injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicenter study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) IV bolus plus a 100 IU/kg 

(1 mg/kg) SC dose followed by an SC injection of 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated 

heparin adjusted based on aPTT for 48 hours. All patients were also treated with  acetylsalicylic acid for a 

minimum of 30 days. The enoxaparin sodium dosing strategy was adjusted for severe renally impaired 

patients and for the elderly of at least 75 years of age. The SC injections of enoxaparin sodium were given 

until hospital discharge or for a maximum of eight days (whichever came first). 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last SC 

administration given less than 8 hours before balloon inflation, IV bolus of 30 IU/ kg (0.3 mg/kg) enoxaparin 

sodium, if the last SC administration given more than 8 hours before balloon inflation. 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p<0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p<0.001). 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p=0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage (a 

measure of net clinical benefit) was significantly lower (p<0.0001) in the enoxaparin sodium group (10.1%) 

as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of treatment 

with enoxaparin sodium. 



 

71 

 

The incidence of major bleeding at 30 days was significantly higher (p<0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated SC administration and after single IV administration. The quantitative determination of anti-Xa 

and anti-IIa pharmacokinetic activities was conducted by validated amidolytic methods. 

 

Absorption 

The absolute bioavailability of enoxaparin sodium after SC injection, based on anti-Xa activity, is close to 

100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after SC injection and achieves 

approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single SC administration of 2,000 IU, 4,000 IU, 

100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 

 

A 3,000 IU (30 mg) IV bolus immediately followed by a 100 IU/kg (1 mg/kg) SC every 12 hours provided 

initial maximum anti-Xa activity level of 1.16 IU/mL (n=16) and average exposure corresponding to 88% of 

steady-state levels. Steady-state is achieved on the second day of treatment. 

 

After repeated SC administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once daily 

regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio about 

15% higher than after a single dose. After repeated SC administration of the 100 IU/kg (1 mg/kg) twice daily 

regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% higher than after a single 

dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 0.52 IU/mL, respectively.  

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated SC administration no accumulation takes 

place. 

 

Plasma anti-IIa activity after SC administration is approximately ten-fold lower than anti-Xa activity. The 

mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following SC injection and 

reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 100 IU/kg (1 mg/kg) twice daily 

and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 

 

Biotransformation 



 

72 

 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour IV infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single SC dose to about 7 hours 

after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal.  However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated SC 

4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine clearance 

<30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated SC 

4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) IV dose however, AUC was two-fold higher than control. 

 

Weight 

After repeated SC 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is marginally 

higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese control 

subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-adjusted 

clearance in obese subjects with SC dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single-SC 4,000 IU (40 mg) dose, 

that anti-Xa exposure is 52% higher in low-weight women (<45 kg) and 27% higher in low-weight men 

(<57 kg) when compared to normal weight control subjects (see section 4.4). 

 

Pharmacokinetic interactions 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week SC toxicity studies both in rats and dogs and at  10 mg/kg/day in the 26-week 

SC and IV toxicity studies both in rats, and monkeys. 



 

73 

 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at SC doses of enoxaparin sodium up to 30 mg/kg/day did not 

reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was found to have no effect 

on fertility or reproductive performance of male and female rats at SC doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Water for injections 

 

6.2 Incompatibilities 
 

SC injection 

Do not mix with other products. 

 

IV (Bolus) Injection (for acute STEMI indication only):  

Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water 

(see section 4.2). 

 

6.3 Shelf life 

 

Pre-filled syringe 

3 years 

 

Diluted medicinal product with sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose 

8 hours 

 

6.4 Special precautions for storage 

 

Store below 25 °C. Do not freeze. 

 

6.5 Nature and contents of container 

 

0.6 mL of solution in: 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 
closed by chlorobutyl rubber stopper and an orange polypropylene plunger rod. The syringe can be 

additionally equipped with needle guard; or 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 

closed by chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe 

Passive needle guard. 

 

Packs of:  

- 2, 6, 10, 30 and 50 pre-filled syringes 
- 2, 6, 10, 12, 20, 24 and 30 pre-filled syringes with needle guard 
- 2 and 10 pre-filled syringes with UltraSafe Passive needle guard 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

INSTRUCTIONS FOR USE: PRE-FILLED SYRINGE  



 

74 

 

 

How to give yourself an injection of Inhixa 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 



 

75 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has a needle guard attached to it in order to protect you from needle stick injury. 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 



 

76 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Push hard the plunger. The needle guard, which is in the form of a plastic cylinder, will be activated 

automatically and it will completely cover the needle. 



 

77 

 

 
10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has UltraSafe Passive needle guard attached to it in order to protect you from needle 

stick injury.  

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
 



 

78 

 

Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
 

To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Let go of the plunger and allow the syringe to move up until the entire needle is guarded and locks 

into place. 

 
 

10)  Drop the used syringe with into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 
 



 

79 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/005 

EU/1/16/1132/006 

EU/1/16/1132/015 

EU/1/16/1132/016 

EU/1/16/1132/026 

EU/1/16/1132/027 

EU/1/16/1132/028 

EU/1/16/1132/037 

EU/1/16/1132/038 

EU/1/16/1132/045 

EU/1/16/1132/046 

EU/1/16/1132/057 

EU/1/16/1132/058 

EU/1/16/1132/083 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

  

http://www.ema.europa.eu/


 

80 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 8,000 IU (80 mg)/0.8 mL solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

10,000 IU/mL (100 mg/mL) solution for injection: 

 

Each pre-filled syringe contains enoxaparin sodium 8,000 IU anti-Xa activity (equivalent to 80 mg) in 

0.8 mL water for injections. 

 

For the full list of excipients, see section 6.1. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerization of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in pre-filled syringe. 

Clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in particular 
those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility at 

increased risk of venous thromboembolism.  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to require 
thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), in 

combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to be 
managed medically or with subsequent percutaneous coronary intervention (PCI). 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 



 

81 

 

 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous (SC) injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk surgery.  

In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 7-

10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the patient no 

longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by SC injection preferably started 12 hours before surgery. If there is a need for 

earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high risk patient 

waiting for a deferred orthopaedic surgery), the last injection should be administered no later than 

12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis 
up to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal 
or pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by SC injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status (e.g. 

mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered SC either as a once daily injection of 150 IU/kg (1.5 mg/kg) or as 

twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by SC injection administered in combination with antiplatelet 

therapy. Treatment should be maintained for a minimum of 2 days and continued until clinical 

stabilization. The usual duration of treatment is 2 to 8 days.  

Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading 

dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75–325 mg/day 

long-term regardless of treatment strategy. 



 

82 

 

 

 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous (IV) 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) SC dose followed by 100 IU/kg (1 mg/kg) 

administered SC every 12 hours (maximum 10,000 IU (100 mg) for each of the first two SC doses). 

Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg to 325 mg once daily) should be 

administered concomitantly unless contraindicated. The recommended duration of treatment is 8 days or 

until hospital discharge, whichever comes first. When administered in conjunction with a thrombolytic 

(fibrin specific or non-fibrin specific), enoxaparin sodium should be given between 15 minutes before 

and 30 minutes after the start of fibrinolytic therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last dose of enoxaparin sodium SC was given less than 

8 hours before balloon inflation, no additional dosing is needed. If the last SC administration 

was given more than 8 hours before balloon inflation, an IV bolus of 30 IU/kg (0.3 mg/kg) 

enoxaparin sodium should be administered. 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established. 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below “renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥75 years of age, an initial IV bolus must not be used. 

Initiate dosing with 75 IU/kg (0.75 mg/kg) SC every 12 hours (maximum 7,500 IU (75 mg) for each of the 

first two SC doses only, followed by 75 IU/kg (0.75 mg/kg) SC dosing for the remaining doses). For dosage 

in elderly patients with impaired kidney function, see below “renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

 Severe renal impairment  
Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease  

 

2,000 IU (20 mg) SC once daily 

Treatment of  DVT and PE 100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of acute STEMI (patients under 75) 

 

 

 

Treatment of acute STEMI (patients over 75) 

1 x 3,000 IU (30 mg) IV bolus plus 100 IU/kg 

(1 mg/kg) body weight SC and then 100 IU/kg 

(1 mg/kg) body weight SC every 24 hours 

 

No IV initial bolus, 100 IU/kg (1 mg/kg) body 

weight SC and then 100 IU/kg (1 mg/kg) body 

weight SC every 24 hours 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

 Moderate and mild renal impairment 



 

83 

 

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30-

50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring is 

advised. 

 

Method of administration  

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thrombo-embolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by SC injection. 

 For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a 
SC injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The pre-filled disposable syringe is ready for immediate use.  

 

The use of a tuberculin syringe or equivalent is recommended when using ampoules or multiple-dose vials to 

assure withdrawal of the appropriate volume of drug. 

 

 SC injection technique: 
Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep SC injection.  

 

Do not expel the air bubble from the syringe before the injection to avoid the loss of drug when using pre-

filled syringes. When the quantity of drug to be injected requires to be adjusted based on the patient’s body 

weight, use the graduated pre-filled syringes to reach the required volume by discarding the excess before 

injection. Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations 

on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. Do not rub the 

injection site after administration. 

 

Note for the pre-filled syringes fitted with an automatic safety system: The safety system is triggered at the 

end of the injection (see instructions in section 6.6). 

 

In case of self-administration, patient should be advised to follow instructions provided in the patient 

information leaflet included in the pack of this medicine. 

 

 IV (bolus) injection (for acute STEMI indication only): 
For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a SC 

injection.  

For IV injection, either the multidose vial or pre-filled syringe can be used. 

Enoxaparin sodium should be administered through an IV line. It should not be mixed or co-administered 

with other medications. To avoid the possible mixture of enoxaparin sodium with other drugs, the IV access 

chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the IV 

bolus administration of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely 

administered with normal saline solution (0.9%) or 5% dextrose in water. 

 

o Initial 3,000 IU (30 mg) bolus 



 

84 

 

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the IV line. 

 

o Additional bolus for PCI when last SC administration was given more than 8 hours before balloon 
inflation 

For patients being managed with PCI, an additional IV bolus of 30 IU/kg (0.3 mg/kg) is to be administered if 

last SC administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either normal saline solution (0.9%) or 5% 

dextrose in water) as follows:  

Withdraw 30 mL from the infusion bag with a syringe and discard the liquid. Inject the complete contents of 

the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe into the 20 mL remaining in the bag. Gently mix 

the contents of the bag. Withdraw the required volume of diluted solution with a syringe for administration 

into the IV line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 



 

85 

 

Volume to be injected through IV line after dilution is completed at a concentration of 300 IU (3 mg) /mL. 

 

Weight 

 

Required dose 

 30 IU/kg (0.3 mg/kg) 

Volume to inject when 

diluted to a final 

concentration of  

 300 IU (3 mg) / mL 

 

[kg] 

 

IU 

 

[mg] 

 

[mL] 

 

45 

 

1350 

 

13.5 

 

4.5 

50 1500 15 5 

55 1650 16.5 5.5 

60 1800 18 6 

65 1950 19.5 6.5 

70 2100 21 7 

75 2250 22.5 7.5 

80 2400 24 8 

85 2550 25.5 8.5 

90 2700 27 9 

95 2850 28.5 9.5 

100 3000 30 10 

105 3150 31.5 10.5 

110 3300 33 11 

115 3450 34.5 11.5 

120 3600 36 12 

125 3750 37.5 12.5 

130 3900 39 13 

135 4050 40.5 13.5 

140 4200 42 14 

145 4350 43.5 14.5 

150 4500 45 15 

  

 

 Arterial line injection: 
It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 

Switch between enoxaparin sodium and oral anticoagulants 

 Switch between enoxaparin sodium and vitamin K antagonists (VKA)  
Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalized 

Ratio (INR)] must be intensified to monitor the effect of VKA. 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

 Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 
For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 



 

86 

 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

- At doses used for prophylaxis 
A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin 

sodium at prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing 

the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with 

neuraxial anaesthesia. 

- At doses used for treatment 
A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin 

sodium at curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg 

(1 mg/kg) twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay 

before catheter placement or removal.  

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH) or to any of the excipients listed in section 6.1; 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

 

4.4 Special warnings and precautions for use 
 

 General 
Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

 History of HIT (>100 days) 



 

87 

 

Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-

induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such a 

case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments 

are considered (e.g. danaparoid sodium or lepirudin). 

 

 Monitoring of platelet counts 
The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 

 

 Haemorrhage 
As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 
- neuro- or ophthalmologic surgery, 
- concomitant use of medications affecting haemostasis (see section 4.5). 

 

 Laboratory tests 
At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

 Spinal/Epidural anaesthesia or lumbar puncture 
Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 



 

88 

 

To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach a 

sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance [15--

30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is more 

prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

 Skin necrosis / cutaneous vasculitis 
Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

 Percutaneous coronary revascularization procedures 
To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If the treatment with 

enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours 

after sheath removal. The site of the procedure should be observed for signs of bleeding or hematoma 

formation. 

 

 Acute infective endocarditis 
Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after a 

careful individual benefit risk assessment. 

 

 Mechanical prosthetic heart valves 
The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 

 Pregnant women with mechanical prosthetic heart valves 
The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg ) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

 Elderly 
No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 



 

89 

 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

 Renal impairment 
In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which increases the 

risk of bleeding. In these patients, careful clinical monitoring is advised, and biological monitoring by anti-

Xa activity measurement might be considered (see sections 4.2 and 5.2). 

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 

 Hepatic impairment 
Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

 Low weight 
An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

 Obese Patients 
Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI >30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 

 

 Hyperkalaemia 
Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  

 Traceability 
LMWHs are biological medicinal products. In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded. 

  

Sodium content 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended:  

 Medicinal products affecting haemostasis (see section 4.4) 
It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 



 

90 

 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 

 

Concomitant use with caution: 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

 Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  

- Systemic glucocorticoids. 
 

 Medicinal products increasing potassium levels: 
Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 

Breast-feeding  

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely.  Inhixa can be used during breastfeeding. 

 

Fertility 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 



 

91 

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) SC once daily for prophylaxis of deep vein thrombosis 

following surgery or in acutely ill medical patients with severely restricted mobility. In treatment of DVT 

with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg (1 mg/kg) SC 

dose every 12 hours or a 150 IU/kg (1.5 mg/kg) SC dose once a day. In the clinical studies for treatment of 

unstable angina and non-Q-wave myocardial infarction, doses were 100 IU/kg (1 mg/kg) SC every 12 hours, 

and in the clinical study for treatment of acute STEMI enoxaparin sodium regimen was a 3,000 IU (30 mg) 

IV bolus followed by 100 IU/kg (1 mg/kg) SC every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see section 4.4 and 'Description of selected adverse reactions' below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 

1/1000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

 Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 

 Rare: Eosinophilia* 

 Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 
complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

 Common: Allergic reaction 

 Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

 Common: Headache* 
 

Vascular disorders 

 Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees of 
neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 

 Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of normality) 

 Uncommon: Hepatocellular liver injury *  

 Rare: Cholestatic liver injury* 
 

Skin and subcutaneous tissue disorders 

 Common: Urticaria, pruritus, erythema  

 Uncommon: Bullous dermatitis 

 Rare: Alopecia* 

 Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena have 
been usually preceded by purpura or erythematous plaques, infiltrated and painful). 

Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 

resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

 Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 



 

92 

 

General disorders and administration site conditions 

 Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

 Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

 Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting 

haemostasis (see sections 4.4 and 4.5). 

 

System 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

 

Blood 

and 

lymphatic 

system 

disorders 

Very common: 

Haemorrhage 
α
 

  

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
  

Very common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and 

gastro-intestinal haemorrhage. 

 

Thrombocytopenia and thrombocytosis 

 

Syste

m 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymph

atic 

system 

disord

ers 

Very common: 

Thrombocytosi

s
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 
 

Very common:    

Thrombocytosi

s 
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 

Common:  

Thrombocytosi

s
β
 

Thrombocytop

enia 

Very rare:     

Immuno-

allergic 

thrombocytope

nia 
β
: Platelet increased >400 G/L  

 



 

93 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

Accidental overdose with enoxaparin sodium after IV, extracorporeal or SC administration may lead to 

haemorrhagic complications. Following oral administration of even large doses, it is unlikely that enoxaparin 

sodium will be absorbed. 

 

Management 

The anticoagulant effects can be largely neutralized by the slow IV injection of protamine. The dose of 

protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the anticoagulant 

effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the previous 

8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be administered if 

enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it 

has been determined that a second dose of protamine is required. After 12 hours of the enoxaparin sodium 

injection, protamine administration may not be required. However, even with high doses of protamine, the 

anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 60%) (see the 

prescribing information for protamine salts). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

Pharmacodynamic effects 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/


 

94 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

 Extended prophylaxis of VTE following orthopaedic surgery  
In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 179 

patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin sodium 

4,000 IU (40 mg) SC, were randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU 

(40 mg) (n=90) once a day SC or to placebo (n=89) for 3 weeks. The incidence of DVT during extended 

prophylaxis was significantly lower for enoxaparin sodium compared to placebo, no PE was reported. No 

major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

once a day SC 

n (%) 

All Treated Extended Prophylaxis 

Patients 
90 (100) 89 (100) 

Total VTE 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)*  18 (20.2) 

 Proximal DVT (%) 5 (5.6)
# 
 7 (8.8) 

*p value versus placebo =0.008 

#p value versus placebo =0.537 

 

 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) SC were randomized to a 

post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n=131) once a day SC or to placebo 

(n=131) for 3 weeks. Similar to the first study the incidence of VTE during extended prophylaxis was 

significantly lower for enoxaparin sodium compared to placebo for both total VTE (enoxaparin sodium 21 

[16%] versus placebo 45 [34.4%]; p=0.001) and proximal DVT (enoxaparin sodium 8 [6.1%] versus placebo 

28 [21.4%]; p=<0.001). No difference in major bleeding was found between the enoxaparin sodium and the 

placebo group. 

 

 Extended prophylaxis of DVT following cancer surgery 
A double-blind, multicenter trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) SC) daily for 6 to 10 days and were 

then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. Bilateral 

venography was performed between days 25 and 31, or sooner if symptoms of venous thromboembolism 

occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis for four weeks after 

surgery for abdominal or pelvic cancer significantly reduced the incidence of venographically demonstrated 

thrombosis, as compared with enoxaparin sodium prophylaxis for one week. The rates of venous 

thromboembolism at the end of the double-blind phase were 12.0 % (n=20) in the placebo group and 4.8% 

(n=8) in the enoxaparin sodium group; p=0.02. This difference persisted at three months [13.8% vs. 5.5% 

(n=23 vs 9), p=0.01]. There were no differences in the rates of bleeding or other complications during the 

double-blind or follow-up periods. 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicenter, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day SC was compared to placebo in the prophylaxis of DVT in medical patients with 

severely restricted mobility during acute illness (defined as walking distance of <10 meters for ≤3 days). 

This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&audience=consumer#footnote-32


 

95 

 

least one VTE risk factor (age ≥75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day SC, enoxaparin 

sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are provided 

in the table below. 

 

 Enoxaparin 

sodium  

2,000 IU (20 mg) 

once a day SC 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

 

n (%) 

All Treated Medical 

Patients During Acute 

Illness 

287 (100) 291(100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5)  40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 

VTE = Venous thromboembolic events which included DVT, PE, and death considered to 

be thromboembolic in origin 

* p value versus placebo =0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicenter, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day SC, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours SC, or (iii) heparin IV bolus 

(5,000 IU) followed by a continuous infusion (administered to achieve an aPTT of 55 to 85 seconds). A total 

of 900 patients were randomized in the study and all patients were treated. All patients also received warfarin 

sodium (dose adjusted according to prothrombin time to achieve an INR of 2.0 to 3.0), commencing within 

72 hours of initiation of enoxaparin sodium or standard heparin therapy, and continuing for 90 days. 

Enoxaparin sodium or standard heparin therapy was administered for a minimum of 5 days and until the 

targeted warfarin sodium INR was achieved.  Both enoxaparin sodium regimens were equivalent to standard 

heparin therapy in reducing the risk of recurrent venous thromboembolism (DVT and/or PE). The efficacy 

data are provided in the table below. 

 

 Enoxaparin sodium  

150 IU/kg 

(1.5 mg/kg) once a 

day SC 

n (%) 

Enoxaparin sodium  

100 IU/kg 

(1 mg/kg) twice a 

day SC 

n (%) 

Heparin  

aPTT Adjusted IV 

Therapy 

n (%) 

All Treated DVT 

Patients with or 

without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

 DVT Only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&audience=consumer#footnote-40


 

96 

 

 Proximal DVT 
(%) 

9 (3.0) 6 (1.9) 7 (2.4) 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 

VTE = venous thromboembolic event (DVT and/or PE) 

*The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  
- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicenter study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either SC enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated heparin 

adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 2 days and a maximum of 

8 days, until clinical stabilization, revascularization procedures or hospital discharge. The patients had to be 

followed up to 30 days. In comparison with heparin, enoxaparin sodium significantly reduced the combined 

incidence of angina pectoris, myocardial infarction and death, with a decrease of 19.8 to 16.6% (relative risk 

reduction of 16.2%) on day 14. This reduction in the combined incidence was maintained after 30 days (from 

23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the SC 

injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicenter study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) IV bolus plus a 100 IU/kg 

(1 mg/kg) SC dose followed by an SC injection of 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated 

heparin adjusted based on aPTT for 48 hours. All patients were also treated with  acetylsalicylic acid for a 

minimum of 30 days. The enoxaparin sodium dosing strategy was adjusted for severe renally impaired 

patients and for the elderly of at least 75 years of age. The SC injections of enoxaparin sodium were given 

until hospital discharge or for a maximum of eight days (whichever came first). 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last SC 

administration given less than 8 hours before balloon inflation, IV bolus of 30 IU/ kg (0.3 mg/kg) enoxaparin 

sodium, if the last SC administration given more than 8 hours before balloon inflation. 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p<0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p<0.001). 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p=0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage (a 

measure of net clinical benefit) was significantly lower (p<0.0001) in the enoxaparin sodium group (10.1%) 

as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of treatment 

with enoxaparin sodium. 



 

97 

 

The incidence of major bleeding at 30 days was significantly higher (p<0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated SC administration and after single IV administration. The quantitative determination of anti-Xa 

and anti-IIa pharmacokinetic activities was conducted by validated amidolytic methods. 

 

Absorption 

The absolute bioavailability of enoxaparin sodium after SC injection, based on anti-Xa activity, is close to 

100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after SC injection and achieves 

approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single SC administration of 2,000 IU, 4,000 IU, 

100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 

 

A 3,000 IU (30 mg) IV bolus immediately followed by a 100 IU/kg (1 mg/kg) SC every 12 hours provided 

initial maximum anti-Xa activity level of 1.16 IU/mL (n=16) and average exposure corresponding to 88% of 

steady-state levels. Steady-state is achieved on the second day of treatment. 

 

After repeated SC administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once daily 

regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio about 

15% higher than after a single dose. After repeated SC administration of the 100 IU/kg (1 mg/kg) twice daily 

regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% higher than after a single 

dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 0.52 IU/mL, respectively.  

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated SC administration no accumulation takes 

place. 

 

Plasma anti-IIa activity after SC administration is approximately ten-fold lower than anti-Xa activity. The 

mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following SC injection and 

reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 100 IU/kg (1 mg/kg) twice daily 

and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 

 

Biotransformation 



 

98 

 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour IV infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single SC dose to about 7 hours 

after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal.  However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated SC 

4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine clearance 

<30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated SC 

4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) IV dose however, AUC was two-fold higher than control. 

 

Weight 

After repeated SC 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is marginally 

higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese control 

subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-adjusted 

clearance in obese subjects with SC dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single-SC 4,000 IU (40 mg) dose, 

that anti-Xa exposure is 52% higher in low-weight women (<45 kg) and 27% higher in low-weight men 

(<57 kg) when compared to normal weight control subjects (see section 4.4). 

 

 

Pharmacokinetic interactions 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week SC toxicity studies both in rats and dogs and at  10 mg/kg/day in the 26-week 

SC and IV toxicity studies both in rats, and monkeys. 



 

99 

 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at SC doses of enoxaparin sodium up to 30 mg/kg/day did not 

reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was found to have no effect 

on fertility or reproductive performance of male and female rats at SC doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Water for injections 

 

6.2 Incompatibilities 
 

SC injection 

Do not mix with other products. 

 

IV (Bolus) Injection (for acute STEMI indication only):  

Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water 

(see section 4.2). 

 

6.3 Shelf life 

 

Pre-filled syringe 

3 years 

 

Diluted medicinal product with sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose 

8 hours 

 

6.4 Special precautions for storage 

 

Store below 25 °C. Do not freeze. 

 

6.5 Nature and contents of container 

 

0.8 mL of solution in:  

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 
closed by chlorobutyl rubber stopper and a red polypropylene plunger rod. The syringe can be 

additionally equipped with needle guard; or 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 

closed by chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe 

Passive needle guard. 

. 

 

Packs of:  

- 2, 6, 10, 30 and 50 pre-filled syringes 
- 2, 6, 10, 12, 24 and 30 pre-filled syringes with needle guard 
- 2 and 10 pre-filled syringes with UltraSafe Passive needle guard 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 



 

100 

 

INSTRUCTIONS FOR USE: PRE-FILLED SYRINGE  

 

How to give yourself an injection of Inhixa 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 



 

101 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has a needle guard attached to it in order to protect you from needle stick injury. 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 



 

102 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Push hard the plunger. The needle guard, which is in the form of a plastic cylinder, will be activated 

automatically and it will completely cover the needle. 



 

103 

 

 
10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has UltraSafe Passive needle guard attached to it in order to protect you from needle 

stick injury.  

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
 



 

104 

 

Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
 

To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Let go of the plunger and allow the syringe to move up until the entire needle is guarded and locks 

into place. 

 
 

10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 
 



 

105 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/007 

EU/1/16/1132/008 

EU/1/16/1132/017 

EU/1/16/1132/018 

EU/1/16/1132/029 

EU/1/16/1132/030 

EU/1/16/1132/039 

EU/1/16/1132/040 

EU/1/16/1132/047 

EU/1/16/1132/048 

EU/1/16/1132/059 

EU/1/16/1132/060 

EU/1/16/1132/084 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

  

http://www.ema.europa.eu/


 

106 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 10,000 IU (100 mg)/1 mL solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

10,000 IU/mL (100 mg/mL) solution for injection 

 

Each pre-filled syringe contains enoxaparin sodium 10,000 IU anti-Xa activity (equivalent to 100 mg) in 1 

mL water for injections. 

 

For the full list of excipients, see section 6.1. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerization of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in pre-filled syringe. 

Clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in particular 
those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility at 

increased risk of venous thromboembolism.  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to require 
thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), in 

combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to be 
managed medically or with subsequent percutaneous coronary intervention (PCI). 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 



 

107 

 

 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous (SC) injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk surgery.  

In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 7-

10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the patient no 

longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by SC injection preferably started 12 hours before surgery. If there is a need for 

earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high risk patient 

waiting for a deferred orthopaedic surgery), the last injection should be administered no later than 

12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis 
up to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal 
or pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by SC injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status (e.g. 

mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered SC either as a once daily injection of 150 IU/kg (1.5 mg/kg) or as 

twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by SC injection administered in combination with antiplatelet 

therapy. Treatment should be maintained for a minimum of 2 days and continued until clinical 

stabilization. The usual duration of treatment is 2 to 8 days.  

Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading 

dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75–325 mg/day 

long-term regardless of treatment strategy. 



 

108 

 

 

 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous (IV) 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) SC dose followed by 100 IU/kg (1 mg/kg) 

administered SC every 12 hours (maximum 10,000 IU (100 mg) for each of the first two SC doses). 

Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg to 325 mg once daily) should be 

administered concomitantly unless contraindicated. The recommended duration of treatment is 8 days or 

until hospital discharge, whichever comes first. When administered in conjunction with a thrombolytic 

(fibrin specific or non-fibrin specific), enoxaparin sodium should be given between 15 minutes before 

and 30 minutes after the start of fibrinolytic therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last dose of enoxaparin sodium SC was given less than 

8 hours before balloon inflation, no additional dosing is needed. If the last SC administration 

was given more than 8 hours before balloon inflation, an IV bolus of 30 IU/kg (0.3 mg/kg) 

enoxaparin sodium should be administered. 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established. 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below “renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥75 years of age, an initial IV bolus must not be used. 

Initiate dosing with 75 IU/kg (0.75 mg/kg) SC every 12 hours (maximum 7,500 IU (75 mg) for each of the 

first two SC doses only, followed by 75 IU/kg (0.75 mg/kg) SC dosing for the remaining doses). For dosage 

in elderly patients with impaired kidney function, see below “renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

 Severe renal impairment  
Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease  

 

2,000 IU (20 mg) SC once daily 

Treatment of  DVT and PE 100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight SC once daily 

Treatment of acute STEMI (patients under 75) 

 

 

 

Treatment of acute STEMI (patients over 75) 

1 x 3,000 IU (30 mg) IV bolus plus 100 IU/kg 

(1 mg/kg) body weight SC and then 100 IU/kg 

(1 mg/kg) body weight SC every 24 hours 

 

No IV initial bolus, 100 IU/kg (1 mg/kg) body 

weight SC and then 100 IU/kg (1 mg/kg) body 

weight SC every 24 hours 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

 Moderate and mild renal impairment 



 

109 

 

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30-

50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring is 

advised. 

 

Method of administration  

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thrombo-embolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by SC injection. 

 For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a 
SC injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The pre-filled disposable syringe is ready for immediate use.  

 

The use of a tuberculin syringe or equivalent is recommended when using ampoules or multiple-dose vials to 

assure withdrawal of the appropriate volume of drug. 

 

 SC injection technique: 
Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep SC injection.  

 

Do not expel the air bubble from the syringe before the injection to avoid the loss of drug when using pre-

filled syringes. When the quantity of drug to be injected requires to be adjusted based on the patient’s body 

weight, use the graduated pre-filled syringes to reach the required volume by discarding the excess before 

injection. Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations 

on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. Do not rub the 

injection site after administration. 

 

Note for the pre-filled syringes fitted with an automatic safety system: The safety system is triggered at the 

end of the injection (see instructions in section 6.6). 

 

In case of self-administration, patient should be advised to follow instructions provided in the patient 

information leaflet included in the pack of this medicine. 

 

 IV (bolus) injection (for acute STEMI indication only): 
For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a SC 

injection.  

For IV injection, either the multidose vial or pre-filled syringe can be used. 

Enoxaparin sodium should be administered through an IV line. It should not be mixed or co-administered 

with other medications. To avoid the possible mixture of enoxaparin sodium with other drugs, the IV access 

chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the IV 

bolus administration of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely 

administered with normal saline solution (0.9%) or 5% dextrose in water. 

 

o Initial 3,000 IU (30 mg) bolus 



 

110 

 

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the IV line. 

 

o Additional bolus for PCI when last SC administration was given more than 8 hours before balloon 
inflation 

For patients being managed with PCI, an additional IV bolus of 30 IU/kg (0.3 mg/kg) is to be administered if 

last SC administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either normal saline solution (0.9%) or 5% 

dextrose in water) as follows:  

Withdraw 30 mL from the infusion bag with a syringe and discard the liquid. Inject the complete contents of 

the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe into the 20 mL remaining in the bag. Gently mix 

the contents of the bag. Withdraw the required volume of diluted solution with a syringe for administration 

into the IV line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 



 

111 

 

Volume to be injected through IV line after dilution is completed at a concentration of 300 IU (3 mg) /mL. 

 

Weight 

 

Required dose 

 30 IU/kg (0.3 mg/kg) 

Volume to inject when 

diluted to a final 

concentration of  

 300 IU (3 mg) / mL 

 

[kg] 

 

IU 

 

[mg] 

 

[mL] 

 

45 

 

1350 

 

13.5 

 

4.5 

50 1500 15 5 

55 1650 16.5 5.5 

60 1800 18 6 

65 1950 19.5 6.5 

70 2100 21 7 

75 2250 22.5 7.5 

80 2400 24 8 

85 2550 25.5 8.5 

90 2700 27 9 

95 2850 28.5 9.5 

100 3000 30 10 

105 3150 31.5 10.5 

110 3300 33 11 

115 3450 34.5 11.5 

120 3600 36 12 

125 3750 37.5 12.5 

130 3900 39 13 

135 4050 40.5 13.5 

140 4200 42 14 

145 4350 43.5 14.5 

150 4500 45 15 

  

 

 Arterial line injection: 
It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 

Switch between enoxaparin sodium and oral anticoagulants 

 Switch between enoxaparin sodium and vitamin K antagonists (VKA)  
Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalized 

Ratio (INR)] must be intensified to monitor the effect of VKA. 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

 Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 
For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 



 

112 

 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

- At doses used for prophylaxis 
A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin 

sodium at prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing 

the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with 

neuraxial anaesthesia. 

- At doses used for treatment 
A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin 

sodium at curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of 

puncture/catheter placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg 

(1 mg/kg) twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay 

before catheter placement or removal.  

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH) or to any of the excipients listed in section 6.1; 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

 

4.4 Special warnings and precautions for use 
 

 General 
Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

 History of HIT (>100 days) 



 

113 

 

Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-

induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such a 

case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments 

are considered (e.g. danaparoid sodium or lepirudin). 

 

 Monitoring of platelet counts 
The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 

 

 Haemorrhage 
As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 
- neuro- or ophthalmologic surgery, 
- concomitant use of medications affecting haemostasis (see section 4.5). 

 

 Laboratory tests 
At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

 Spinal/Epidural anaesthesia or lumbar puncture 
Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 



 

114 

 

To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach a 

sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance [15--

30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is more 

prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

 Skin necrosis / cutaneous vasculitis 
Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

 Percutaneous coronary revascularization procedures 
To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If the treatment with 

enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours 

after sheath removal. The site of the procedure should be observed for signs of bleeding or hematoma 

formation. 

 

 Acute infective endocarditis 
Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after a 

careful individual benefit risk assessment. 

 

 Mechanical prosthetic heart valves 
The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 

 Pregnant women with mechanical prosthetic heart valves 
The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg ) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

 Elderly 
No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 



 

115 

 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

 Renal impairment 
In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which increases the 

risk of bleeding. In these patients, careful clinical monitoring is advised, and biological monitoring by anti-

Xa activity measurement might be considered (see sections 4.2 and 5.2). 

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance <15 

mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 

 Hepatic impairment 
Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

 Low weight 
An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

 Obese Patients 
Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI >30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 

 

 Hyperkalaemia 
Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  

 Traceability 
LMWHs are biological medicinal products. In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded. 

  

Sodium content 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended:  

 Medicinal products affecting haemostasis (see section 4.4) 
It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 



 

116 

 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 

 

Concomitant use with caution: 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

 Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  

- Systemic glucocorticoids. 
 

 Medicinal products increasing potassium levels: 
Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 

Breast-feeding  

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely.  Inhixa can be used during breastfeeding. 

 

Fertility 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 



 

117 

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) SC once daily for prophylaxis of deep vein thrombosis 

following surgery or in acutely ill medical patients with severely restricted mobility. In treatment of DVT 

with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg (1 mg/kg) SC 

dose every 12 hours or a 150 IU/kg (1.5 mg/kg) SC dose once a day. In the clinical studies for treatment of 

unstable angina and non-Q-wave myocardial infarction, doses were 100 IU/kg (1 mg/kg) SC every 12 hours, 

and in the clinical study for treatment of acute STEMI enoxaparin sodium regimen was a 3,000 IU (30 mg) 

IV bolus followed by 100 IU/kg (1 mg/kg) SC every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see section 4.4 and 'Description of selected adverse reactions' below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 

1/1000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

 Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 

 Rare: Eosinophilia* 

 Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 
complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

 Common: Allergic reaction 

 Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

 Common: Headache* 
 

Vascular disorders 

 Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees of 
neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 

 Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of normality) 

 Uncommon: Hepatocellular liver injury *  

 Rare: Cholestatic liver injury* 
 

Skin and subcutaneous tissue disorders 

 Common: Urticaria, pruritus, erythema  

 Uncommon: Bullous dermatitis 

 Rare: Alopecia* 

 Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena have 
been usually preceded by purpura or erythematous plaques, infiltrated and painful). 

Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 

resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

 Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 



 

118 

 

General disorders and administration site conditions 

 Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

 Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

 Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting 

haemostasis (see sections 4.4 and 4.5). 

 

System 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

 

Blood 

and 

lymphatic 

system 

disorders 

Very common: 

Haemorrhage 
α
 

  

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
  

Very common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and 

gastro-intestinal haemorrhage. 

 

Thrombocytopenia and thrombocytosis 

 

Syste

m 

Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymph

atic 

system 

disord

ers 

Very common: 

Thrombocytosi

s
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 
 

Very common:    

Thrombocytosi

s 
β
 

 

Common: 

Thrombocytop

enia 

Uncommon: 

Thrombocytop

enia 

Common:  

Thrombocytosi

s
β
 

Thrombocytop

enia 

Very rare:     

Immuno-

allergic 

thrombocytope

nia 
β
: Platelet increased >400 G/L  

 



 

119 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Multiple dose vials containing benzyl alcohol: 

The administration of medicinal product containing benzyl alcohol as a preservative to neonates has been 

associated with a fatal “Gasping Syndrome” (see section 4.3). 

Benzyl alcohol may also cause toxic reactions and anaphylactoid reactions in infants and children up to 3 

years old (see section 4.4). 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

Accidental overdose with enoxaparin sodium after IV, extracorporeal or SC administration may lead to 

haemorrhagic complications. Following oral administration of even large doses, it is unlikely that enoxaparin 

sodium will be absorbed. 

 

Management 

The anticoagulant effects can be largely neutralized by the slow IV injection of protamine. The dose of 

protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the anticoagulant 

effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the previous 

8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be administered if 

enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it 

has been determined that a second dose of protamine is required. After 12 hours of the enoxaparin sodium 

injection, protamine administration may not be required. However, even with high doses of protamine, the 

anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 60%) (see the 

prescribing information for protamine salts). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

Pharmacodynamic effects 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
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120 

 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

 Extended prophylaxis of VTE following orthopaedic surgery  
In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 179 

patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin sodium 

4,000 IU (40 mg) SC, were randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU 

(40 mg) (n=90) once a day SC or to placebo (n=89) for 3 weeks. The incidence of DVT during extended 

prophylaxis was significantly lower for enoxaparin sodium compared to placebo, no PE was reported. No 

major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

once a day SC 

n (%) 

All Treated Extended Prophylaxis 

Patients 
90 (100) 89 (100) 

Total VTE 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)*  18 (20.2) 

 Proximal DVT (%) 5 (5.6)
# 
 7 (8.8) 

*p value versus placebo =0.008 

#p value versus placebo =0.537 

 

 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) SC were randomized to a 

post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n=131) once a day SC or to placebo 

(n=131) for 3 weeks. Similar to the first study the incidence of VTE during extended prophylaxis was 

significantly lower for enoxaparin sodium compared to placebo for both total VTE (enoxaparin sodium 21 

[16%] versus placebo 45 [34.4%]; p=0.001) and proximal DVT (enoxaparin sodium 8 [6.1%] versus placebo 

28 [21.4%]; p=<0.001). No difference in major bleeding was found between the enoxaparin sodium and the 

placebo group. 

 

 Extended prophylaxis of DVT following cancer surgery 
A double-blind, multicenter trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) SC) daily for 6 to 10 days and were 

then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. Bilateral 

venography was performed between days 25 and 31, or sooner if symptoms of venous thromboembolism 

occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis for four weeks after 

surgery for abdominal or pelvic cancer significantly reduced the incidence of venographically demonstrated 

thrombosis, as compared with enoxaparin sodium prophylaxis for one week. The rates of venous 

thromboembolism at the end of the double-blind phase were 12.0 % (n=20) in the placebo group and 4.8% 

(n=8) in the enoxaparin sodium group; p=0.02. This difference persisted at three months [13.8% vs. 5.5% 

(n=23 vs 9), p=0.01]. There were no differences in the rates of bleeding or other complications during the 

double-blind or follow-up periods. 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicenter, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day SC was compared to placebo in the prophylaxis of DVT in medical patients with 

severely restricted mobility during acute illness (defined as walking distance of <10 meters for ≤3 days). 

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121 

 

This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

least one VTE risk factor (age ≥75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day SC, enoxaparin 

sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are provided 

in the table below. 

 

 Enoxaparin 

sodium  

2,000 IU (20 mg) 

once a day SC 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg) 

once a day SC 

n (%) 

Placebo  

 

n (%) 

All Treated Medical 

Patients During Acute 

Illness 

287 (100) 291(100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5)  40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 

VTE = Venous thromboembolic events which included DVT, PE, and death considered to 

be thromboembolic in origin 

* p value versus placebo =0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicenter, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day SC, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours SC, or (iii) heparin IV bolus 

(5,000 IU) followed by a continuous infusion (administered to achieve an aPTT of 55 to 85 seconds). A total 

of 900 patients were randomized in the study and all patients were treated. All patients also received warfarin 

sodium (dose adjusted according to prothrombin time to achieve an INR of 2.0 to 3.0), commencing within 

72 hours of initiation of enoxaparin sodium or standard heparin therapy, and continuing for 90 days. 

Enoxaparin sodium or standard heparin therapy was administered for a minimum of 5 days and until the 

targeted warfarin sodium INR was achieved.  Both enoxaparin sodium regimens were equivalent to standard 

heparin therapy in reducing the risk of recurrent venous thromboembolism (DVT and/or PE). The efficacy 

data are provided in the table below. 

 

 Enoxaparin sodium  

150 IU/kg 

(1.5 mg/kg) once a 

day SC 

n (%) 

Enoxaparin sodium  

100 IU/kg 

(1 mg/kg) twice a 

day SC 

n (%) 

Heparin  

aPTT Adjusted IV 

Therapy 

n (%) 

All Treated DVT 

Patients with or 

without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&audience=consumer#footnote-40


 

122 

 

 DVT Only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

 Proximal DVT 
(%) 

9 (3.0) 6 (1.9) 7 (2.4) 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 

VTE = venous thromboembolic event (DVT and/or PE) 

*The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  
- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicenter study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either SC enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated heparin 

adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 2 days and a maximum of 

8 days, until clinical stabilization, revascularization procedures or hospital discharge. The patients had to be 

followed up to 30 days. In comparison with heparin, enoxaparin sodium significantly reduced the combined 

incidence of angina pectoris, myocardial infarction and death, with a decrease of 19.8 to 16.6% (relative risk 

reduction of 16.2%) on day 14. This reduction in the combined incidence was maintained after 30 days (from 

23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the SC 

injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicenter study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) IV bolus plus a 100 IU/kg 

(1 mg/kg) SC dose followed by an SC injection of 100 IU/kg (1 mg/kg) every 12 hours or IV unfractionated 

heparin adjusted based on aPTT for 48 hours. All patients were also treated with  acetylsalicylic acid for a 

minimum of 30 days. The enoxaparin sodium dosing strategy was adjusted for severe renally impaired 

patients and for the elderly of at least 75 years of age. The SC injections of enoxaparin sodium were given 

until hospital discharge or for a maximum of eight days (whichever came first). 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last SC 

administration given less than 8 hours before balloon inflation, IV bolus of 30 IU/ kg (0.3 mg/kg) enoxaparin 

sodium, if the last SC administration given more than 8 hours before balloon inflation. 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p<0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p<0.001). 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p=0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage (a 

measure of net clinical benefit) was significantly lower (p<0.0001) in the enoxaparin sodium group (10.1%) 



 

123 

 

as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of treatment 

with enoxaparin sodium. 

The incidence of major bleeding at 30 days was significantly higher (p<0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated SC administration and after single IV administration. The quantitative determination of anti-Xa 

and anti-IIa pharmacokinetic activities was conducted by validated amidolytic methods. 

 

Absorption 

The absolute bioavailability of enoxaparin sodium after SC injection, based on anti-Xa activity, is close to 

100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after SC injection and achieves 

approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single SC administration of 2,000 IU, 4,000 IU, 

100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 

 

A 3,000 IU (30 mg) IV bolus immediately followed by a 100 IU/kg (1 mg/kg) SC every 12 hours provided 

initial maximum anti-Xa activity level of 1.16 IU/mL (n=16) and average exposure corresponding to 88% of 

steady-state levels. Steady-state is achieved on the second day of treatment. 

 

After repeated SC administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once daily 

regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio about 

15% higher than after a single dose. After repeated SC administration of the 100 IU/kg (1 mg/kg) twice daily 

regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% higher than after a single 

dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 0.52 IU/mL, respectively.  

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated SC administration no accumulation takes 

place. 

 

Plasma anti-IIa activity after SC administration is approximately ten-fold lower than anti-Xa activity. The 

mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following SC injection and 

reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 100 IU/kg (1 mg/kg) twice daily 

and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 



 

124 

 

 

Biotransformation 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour IV infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single SC dose to about 7 hours 

after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal.  However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated SC 

4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine clearance 

<30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated SC 

4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) IV dose however, AUC was two-fold higher than control. 

 

Weight 

After repeated SC 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is marginally 

higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese control 

subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-adjusted 

clearance in obese subjects with SC dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single-SC 4,000 IU (40 mg) dose, 

that anti-Xa exposure is 52% higher in low-weight women (<45 kg) and 27% higher in low-weight men 

(<57 kg) when compared to normal weight control subjects (see section 4.4). 

 

Pharmacokinetic interactions 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 



 

125 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week SC toxicity studies both in rats and dogs and at  10 mg/kg/day in the 26-week 

SC and IV toxicity studies both in rats, and monkeys. 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at SC doses of enoxaparin sodium up to 30 mg/kg/day did not 

reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was found to have no effect 

on fertility or reproductive performance of male and female rats at SC doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Water for injections 

 

6.2 Incompatibilities 
 

SC injection 

Do not mix with other products. 

 

IV (Bolus) Injection (for acute STEMI indication only):  

Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water 

(see section 4.2). 

 

6.3 Shelf life 

 

Pre-filled syringe 

3 years 

 

Diluted medicinal product with sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose 

8 hours 

 

6.4 Special precautions for storage 

 

Store below 25 °C. Do not freeze. 

 

6.5 Nature and contents of container 

 

1 mL of solution in: 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 
closed by chlorobutyl rubber stopper and a black polypropylene plunger rod. The syringe can be 

additionally equipped with needle guard; or 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 

closed by chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe 

Passive needle guard. 

 

 

Packs of:  

- 2, 6, 10, 30, 50 and 90 pre-filled syringes 
- 2, 6, 10, 12, 24 and 30 pre-filled syringes with needle guard 
- 2 and 10 pre-filled syringes with UltraSafe Passive needle guard 



 

126 

 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

INSTRUCTIONS FOR USE: PRE-FILLED SYRINGE  

 

How to give yourself an injection of Inhixa 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 



 

127 

 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has a needle guard attached to it in order to protect you from needle stick injury. 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 



 

128 

 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Push hard the plunger. The needle guard, which is in the form of a plastic cylinder, will be activated 

automatically and it will completely cover the needle. 



 

129 

 

 
10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has UltraSafe Passive needle guard attached to it in order to protect you from needle 

stick injury.  

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
 



 

130 

 

Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
 

To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Let go of the plunger and allow the syringe to move up until the entire needle is guarded and locks 

into place. 

 
 

10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 
 



 

131 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/009 

EU/1/16/1132/010 

EU/1/16/1132/019 

EU/1/16/1132/020 

EU/1/16/1132/022 

EU/1/16/1132/031 

EU/1/16/1132/032 

EU/1/16/1132/041 

EU/1/16/1132/042 

EU/1/16/1132/049 

EU/1/16/1132/050 

EU/1/16/1132/061 

EU/1/16/1132/062 

EU/1/16/1132/063 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

  

http://www.ema.europa.eu/


 

132 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 12,000 IU (120 mg)/0.8 mL solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each pre-filled syringe contains enoxaparin sodium 12,000 IU anti-Xa activity (equivalent to 120 mg) in 

0.8 mL water for injections. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerisation of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in pre-filled syringe. 

Clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in 
particular those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility 

at increased risk of venous thromboembolism.  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to 
require thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), 

in combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to 
be managed medically or with subsequent percutaneous coronary intervention (PCI). 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 

 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk 

surgery.  



 

133 

 

In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 

7-10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the 

patient no longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by subcutaneous injection preferably started 12 hours before surgery. If there 

is a need for earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high 

risk patient waiting for a deferred orthopaedic surgery), the last injection should be administered no 

later than 12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis 
up to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or 
pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by subcutaneous injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status 

(e.g. mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered subcutaneously either as a once daily injection of 150 IU/kg 

(1.5 mg/kg) or as twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by subcutaneous injection administered in combination with 

antiplatelet therapy. Treatment should be maintained for a minimum of 2 days and continued until 

clinical stabilization. The usual duration of treatment is 2 to 8 days.  

Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading 

dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75–325 mg/day 

long-term regardless of treatment strategy. 

 

 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) subcutaneous dose followed by 100 IU/kg 



 

134 

 

(1 mg/kg) administered subcutaneously every 12 hours (maximum 10,000 IU (100 mg) for each of the 

first two subcutaneous doses). Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg 

to 325 mg once daily) should be administered concomitantly unless contraindicated. The 

recommended duration of treatment is 8 days or until hospital discharge, whichever comes first. When 

administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific), enoxaparin 

sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic 

therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last dose of enoxaparin sodium was given less than 

8 hours before balloon inflation, no additional dosing is needed. If the last subcutaneous 

administration was given more than 8 hours before balloon inflation, an intravenous bolus of 

30 IU/kg (0.3 mg/kg) enoxaparin sodium should be administered. 

 

Special populations 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established. 

No data are available. 

 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below “renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥ 75 years of age, an initial intravenous bolus must not be 

used. Initiate dosing with 75 IU/kg (0.75 mg/kg) subcutaneous injection every 12 hours (maximum 7,500 IU 

(75 mg) for each of the first two subcutaneous doses only, followed by 75 IU/kg (0.75 mg/kg) subcutaneous 

dosing for the remaining doses). For dosage in elderly patients with impaired kidney function, see below 

“renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

Severe renal impairment  

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 

< 15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease 2,000 IU (20 mg) subcutaneously once daily 

Treatment of DVT and PE 100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of acute STEMI (patients under 75) 

 

 

Treatment of acute STEMI (patients over 75) 

1 x 3,000 IU (30 mg) intravenous bolus plus 100 IU/kg 

(1 mg/kg) body weight subcutaneously and then 100 IU/kg 

(1 mg/kg) body weight subcutaneously every 24 hours 

No intravenous initial bolus, 100 IU/kg (1 mg/kg) body 

weight subcutaneously and then 100 IU/kg (1 mg/kg) body 

weight subcutaneously every 24 hours 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

Moderate and mild renal impairment 

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 

30-50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring 

is advised. 

 



 

135 

 

Method of administration  

 

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thrombo-embolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by subcutaneous 

injection. 

 For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately 
followed by a subcutaneous injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The pre-filled disposable syringe is ready for immediate use.  

 

The use of a tuberculin syringe or equivalent is recommended when using ampoules or multiple-dose vials to 

assure withdrawal of the appropriate volume of drug. 

 

Subcutaneous injection technique 

Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep subcutaneous injection.  

 

The air bubble should not be expelled from the syringe before the injection to avoid the loss of drug when 

using pre-filled syringes. When the quantity of drug to be injected requires to be adjusted based on the 

patient’s body weight, the graduated pre-filled syringes should be used to reach the required volume by 

discarding the excess before injection. In some cases it is not possible to achieve an exact dose due to the 

graduations on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. The injection 

site should not be rubbed after administration. 

 

Note for the pre-filled syringes fitted with an automatic safety system: The safety system is triggered at the 

end of the injection (see instructions in section 6.6). 

 

In case of self-administration, patient should be advised to follow instructions provided in the patient 

information leaflet included in the pack of this medicine. 

 

Intravenous (bolus) injection (for acute STEMI indication only) 

For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately followed 

by a subcutaneous injection.  

For intravenous injection, either the multidose vial or pre-filled syringe can be used. 

Enoxaparin sodium should be administered through an intravenous line. It should not be mixed or 

co-administered with other medications. To avoid the possible mixture of enoxaparin sodium with other 

drugs, the intravenous access chosen should be flushed with a sufficient amount of sodium chloride or 

dextrose solution prior to and following the intravenous bolus administration of enoxaparin sodium to clear 

the port of drug. Enoxaparin sodium may be safely administered with sodium chloride 9 mg/ml (0.9%) 

solution for injection or 5% dextrose in water. 

 

Initial 3,000 IU (30 mg) bolus 

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the intravenous line. 

 



 

136 

 

Additional bolus for PCI when last subcutaneous administration was given more than 8 hours before balloon 

inflation 

For patients being managed with PCI, an additional intravenous bolus of 30 IU/kg (0.3 mg/kg) is to be 

administered if last subcutaneous administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either sodium chloride 9 mg/ml (0.9%) solution for 

injection or 5% dextrose in water) as follows:  

30 mL of solution should be withdrawn from the infusion bag with a syringe and discarded. The complete 

contents of the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe should be injected into the 20 mL 

remaining in the bag. The contents of the bag should be gently mixed. Then, the required volume of diluted 

solution should be withdrawn with a syringe for administration into the intravenous line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 

Volume to be injected through intravenous line after dilution is completed at a concentration of 

300 IU (3 mg)/mL. 

 

Weight 
Required dose  

30 IU/kg (0.3 mg/kg) 

Volume to inject when diluted 

to a final concentration of  

300 IU (3 mg)/mL 

[kg] IU [mg] [mL] 

45 1350 13.5 4.5 

50 1500 15 5 

55 1650 16.5 5.5 

60 1800 18 6 

65 1950 19.5 6.5 

70 2100 21 7 

75 2250 22.5 7.5 

80 2400 24 8 

85 2550 25.5 8.5 

90 2700 27 9 

95 2850 28.5 9.5 

100 3000 30 10 

105 3150 31.5 10.5 

110 3300 33 11 

115 3450 34.5 11.5 

120 3600 36 12 

125 3750 37.5 12.5 

130 3900 39 13 

135 4050 40.5 13.5 

140 4200 42 14 

145 4350 43.5 14.5 

150 4500 45 15 

 

Arterial line injection 

It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 

Switch between enoxaparin sodium and oral anticoagulants 

Switch between enoxaparin sodium and vitamin K antagonists (VKA)  

Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalized Ratio 

(INR)] must be intensified to monitor the effect of VKA. 



 

137 

 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 

For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

 

At doses used for prophylaxis 

A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin sodium at 

prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with neuraxial 

anaesthesia. 

 

At doses used for treatment 

A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin sodium at 

curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg (1 mg/kg) 

twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay before catheter 

placement or removal.  

 

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH) or to any of the excipients listed in section 6.1; 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 



 

138 

 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

 

4.4 Special warnings and precautions for use 
 

General 

Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

History of HIT (> 100 days) 

Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (> 100 days) of 

heparin-induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in 

such a case must be made only after a careful benefit risk assessment and after non-heparin alternative 

treatments are considered (e.g. danaparoid sodium or lepirudin). 

 
Monitoring of platelet counts 

The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 
 

Haemorrhage 

As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 

- neuro- or ophthalmologic surgery, 
- concomitant use of medications affecting haemostasis (see section 4.5). 

 

Laboratory tests 

At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 



 

139 

 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

Spinal/Epidural anaesthesia or lumbar puncture 

Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 

To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach 

a sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance 

[15-30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is 

more prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

Skin necrosis / cutaneous vasculitis 

Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

Percutaneous coronary revascularization procedures 

To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last intravenous/subcutaneous enoxaparin sodium injection. If the 

treatment with enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 

6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or 

hematoma formation. 

 

Acute infective endocarditis 

Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after 

a careful individual benefit risk assessment. 

 

Mechanical prosthetic heart valves 

The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 



 

140 

 

Pregnant women with mechanical prosthetic heart valves 

The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

Elderly 

No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

Renal impairment 

In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which increases the 

risk of bleeding. In these patients, careful clinical monitoring is advised, and biological monitoring by 

anti-Xa activity measurement might be considered (see sections 4.2 and 5.2). 

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 

< 15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 

Hepatic impairment 

Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

Low weight 

An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (< 45 kg) and low-weight men (< 57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

Obese Patients 

Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI > 30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 
 

Hyperkalaemia 

Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  

Traceability 

LMWHs are biological medicinal products. In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded. 

  

Sodium content 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 



 

141 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended 

 

Medicinal products affecting haemostasis (see section 4.4) 

It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 

 

Concomitant use with caution 

 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  
- Systemic glucocorticoids. 

 

Medicinal products increasing potassium levels 

Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 

Breast-feeding  

 

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely. Inhixa can be used during breastfeeding. 

 

Fertility 

 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 



 

142 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) subcutaneously once daily for prophylaxis of deep vein 

thrombosis following surgery or in acutely ill medical patients with severely restricted mobility. In treatment 

of DVT with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg 

(1 mg/kg) subcutaneous dose every 12 hours or a 150 IU/kg (1.5 mg/kg) subcutaneous dose once a day. In 

the clinical studies for treatment of unstable angina and non-Q-wave myocardial infarction, doses were 

100 IU/kg (1 mg/kg) subcutaneously every 12 hours, and in the clinical study for treatment of acute STEMI 

enoxaparin sodium regimen was a 3,000 IU (30 mg) intravenous bolus followed by 100 IU/kg (1 mg/kg) 

subcutaneously every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see section 4.4 and 'Description of selected adverse reactions' below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 

(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

 Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 

 Rare: Eosinophilia* 

 Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 
complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

 Common: Allergic reaction 

 Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

 Common: Headache* 
 

Vascular disorders 

 Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees 
of neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 



 

143 

 

 Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of 
normality) 

 Uncommon: Hepatocellular liver injury*  

 Rare: Cholestatic liver injury* 
 

Skin and subcutaneous tissue disorders 

 Common: Urticaria, pruritus, erythema  

 Uncommon: Bullous dermatitis 

 Rare: Alopecia* 

 Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena 
have been usually preceded by purpura or erythematous plaques, infiltrated and painful). 

 Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 
resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

 Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 

General disorders and administration site conditions 

 Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

 Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

 Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting 

haemostasis (see sections 4.4 and 4.5). 

 

System Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical 

patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood and 

lymphatic 

system 

disorders 

Very common: 

Haemorrhage 
α
 

 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
  

Very common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and 

gastro-intestinal haemorrhage. 

 



 

144 

 

Thrombocytopenia and thrombocytosis 

System Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical 

patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood and 

lymphatic 

system 

disorders 

Very common: 

Thrombocytosis
β
 

 

 

Common: 

Thrombo-

cytopenia 

Uncommon: 

Thrombo-

cytopenia 

 

Very common:    

Thrombo-

cytosis
β
 

 

Common: 

Thrombo-

cytopenia 

Uncommon: 

Thrombo-

cytopenia 

Common:  

Thrombocytosis
β
 

Thrombo-

cytopenia 

Very rare:     

Immuno-allergic 

thrombo-

cytopenia 
β
: Platelet increased > 400 G/L  

 

Paediatric population 

 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

 

Accidental overdose with enoxaparin sodium after intravenous, extracorporeal or subcutaneous 

administration may lead to haemorrhagic complications. Following oral administration of even large doses, it 

is unlikely that enoxaparin sodium will be absorbed. 

 

Management 

 

The anticoagulant effects can be largely neutralized by the slow intravenous injection of protamine. The dose 

of protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the 

anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the 

previous 8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be 

administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine 

administration, or if it has been determined that a second dose of protamine is required. After 12 hours of the 

enoxaparin sodium injection, protamine administration may not be required. However, even with high doses 

of protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 

60%) (see the prescribing information for protamine salts). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/


 

145 

 

Pharmacodynamic effects 

 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

Extended prophylaxis of VTE following orthopaedic surgery  

In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 

179 patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin 

sodium 4,000 IU (40 mg) subcutaneously, were randomized to a post-discharge regimen of either enoxaparin 

sodium 4,000 IU (40 mg) (n = 90) once a day subcutaneously or to placebo (n = 89) for 3 weeks. The 

incidence of DVT during extended prophylaxis was significantly lower for enoxaparin sodium compared to 

placebo, no PE was reported. No major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) once a day 

subcutaneously 

n (%) 

Placebo  

once a day 

subcutaneously 

n (%) 

All Treated Extended Prophylaxis Patients 90 (100) 89 (100) 

Total VTE 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)*  18 (20.2) 

 Proximal DVT (%) 5 (5.6)
# 
 7 (8.8) 

*p value versus placebo = 0.008 

#p value versus placebo = 0.537 

 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) subcutaneously were 

randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n = 131) once a day 

subcutaneously or to placebo (n = 131) for 3 weeks. Similar to the first study the incidence of VTE during 

extended prophylaxis was significantly lower for enoxaparin sodium compared to placebo for both total VTE 

(enoxaparin sodium 21 [16%] versus placebo 45 [34.4%]; p = 0.001) and proximal DVT (enoxaparin sodium 

8 [6.1%] versus placebo 28 [21.4%]; p =< 0.001). No difference in major bleeding was found between the 

enoxaparin sodium and the placebo group. 

 

Extended prophylaxis of DVT following cancer surgery 

A double-blind, multicentre trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) subcutaneously) daily for 6 to 10 days 

and were then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. 

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&audience=consumer#footnote-32


 

146 

 

Bilateral venography was performed between days 25 and 31, or sooner if symptoms of venous 

thromboembolism occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis 

for four weeks after surgery for abdominal or pelvic cancer significantly reduced the incidence of 

venographically demonstrated thrombosis, as compared with enoxaparin sodium prophylaxis for one week. 

The rates of venous thromboembolism at the end of the double-blind phase were 12.0 % (n = 20) in the 

placebo group and 4.8% (n = 8) in the enoxaparin sodium group; p = 0.02. This difference persisted at three 

months [13.8% vs. 5.5% (n = 23 vs 9), p = 0.01]. There were no differences in the rates of bleeding or other 

complications during the double-blind or follow-up periods. 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicentre, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day subcutaneously was compared to placebo in the prophylaxis of DVT in medical patients 

with severely restricted mobility during acute illness (defined as walking distance of < 10 meters for 

≤ 3 days). This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

least one VTE risk factor (age ≥ 75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day subcutaneously, 

enoxaparin sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are 

provided in the table below. 

 

 Enoxaparin sodium  

2,000 IU (20 mg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg) 

once a day 

subcutaneously 

n (%) 

Placebo  

 

 

n (%) 

All Treated Medical Patients 

During Acute Illness 

287 (100) 291 (100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5)  40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 
VTE = Venous thromboembolic events which included DVT, PE, and death considered to be thromboembolic in origin 

* p value versus placebo = 0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicentre, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day subcutaneously, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours subcutaneously, 

or (iii) heparin intravenous bolus (5,000 IU) followed by a continuous infusion (administered to achieve an 

aPTT of 55 to 85 seconds). A total of 900 patients were randomized in the study and all patients were 

treated. All patients also received warfarin sodium (dose adjusted according to prothrombin time to achieve 

an INR of 2.0 to 3.0), commencing within 72 hours of initiation of enoxaparin sodium or standard heparin 

therapy, and continuing for 90 days. Enoxaparin sodium or standard heparin therapy was administered for a 

minimum of 5 days and until the targeted warfarin sodium INR was achieved.  Both enoxaparin sodium 

regimens were equivalent to standard heparin therapy in reducing the risk of recurrent venous 

thromboembolism (DVT and/or PE). The efficacy data are provided in the table below. 

 



 

147 

 

 Enoxaparin sodium  
150 IU/kg (1.5 mg/kg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

100 IU/kg (1 mg/kg) 

twice a day 

subcutaneously 

n (%) 

Heparin  

aPTT Adjusted 

Intravenous Therapy 

n (%) 

All Treated DVT Patients 

with or without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

 DVT Only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

 Proximal DVT (%) 9 (3.0) 6 (1.9) 7 (2.4) 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 
VTE = venous thromboembolic event (DVT and/or PE) 

*The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  

- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicentre study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either subcutaneous enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or intravenous 

unfractionated heparin adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 

2 days and a maximum of 8 days, until clinical stabilization, revascularization procedures or hospital 

discharge. The patients had to be followed up to 30 days. In comparison with heparin, enoxaparin sodium 

significantly reduced the combined incidence of angina pectoris, myocardial infarction and death, with a 

decrease of 19.8 to 16.6% (relative risk reduction of 16.2%) on day 14. This reduction in the combined 

incidence was maintained after 30 days (from 23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the 

subcutaneous injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicentre study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) intravenous bolus plus 

a 100 IU/kg (1 mg/kg) subcutaneous dose followed by an subcutaneous injection of 100 IU/kg (1 mg/kg) 

every 12 hours or intravenous unfractionated heparin adjusted based on aPTT for 48 hours. All patients were 

also treated with acetylsalicylic acid for a minimum of 30 days. The enoxaparin sodium dosing strategy was 

adjusted for severe renally impaired patients and for the elderly of at least 75 years of age. The subcutaneous 

injections of enoxaparin sodium were given until hospital discharge or for a maximum of eight days 

(whichever came first). 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last 

subcutaneous administration given less than 8 hours before balloon inflation, intravenous bolus of 30 IU/ kg 

(0.3 mg/kg) enoxaparin sodium, if the last subcutaneous administration given more than 8 hours before 

balloon inflation. 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p < 0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p < 0.001). 



 

148 

 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p = 0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage 

(a measure of net clinical benefit) was significantly lower (p < 0.0001) in the enoxaparin sodium group 

(10.1%) as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of 

treatment with enoxaparin sodium. 

The incidence of major bleeding at 30 days was significantly higher (p < 0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated subcutaneous administration and after single intravenous administration. The quantitative 

determination of anti-Xa and anti-IIa pharmacokinetic activities was conducted by validated amidolytic 

methods. 

 

Absorption 

 

The absolute bioavailability of enoxaparin sodium after subcutaneous injection, based on anti-Xa activity, is 

close to 100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after subcutaneous injection and 

achieves approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single subcutaneous administration of 

2,000 IU, 4,000 IU, 100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 

 

A 3,000 IU (30 mg) intravenous bolus immediately followed by a 100 IU/kg (1 mg/kg) subcutaneous every 

12 hours provided initial maximum anti-Xa activity level of 1.16 IU/mL (n = 16) and average exposure 

corresponding to 88% of steady-state levels. Steady-state is achieved on the second day of treatment. 

 

After repeated subcutaneous administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once 

daily regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio 

about 15% higher than after a single dose. After repeated subcutaneous administration of the 100 IU/kg 

(1 mg/kg) twice daily regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% 

higher than after a single dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 

0.52 IU/mL, respectively.  

 



 

149 

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated subcutaneous administration no 

accumulation takes place. 

 

Plasma anti-IIa activity after subcutaneous administration is approximately ten-fold lower than anti-Xa 

activity. The mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following 

subcutaneous injection and reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 

100 IU/kg (1 mg/kg) twice daily and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 

 

Biotransformation 

 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerisation to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour intravenous infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single subcutaneous dose to about 

7 hours after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal.  However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine 

clearance < 30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) intravenous dose however, AUC was two-fold higher than control. 

 



 

150 

 

Weight 

After repeated subcutaneous 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is 

marginally higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese 

control subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-

adjusted clearance in obese subjects with subcutaneous dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single-subcutaneous 4,000 IU 

(40 mg) dose, that anti-Xa exposure is 52% higher in low-weight women (< 45 kg) and 27% higher in 

low-weight men (< 57 kg) when compared to normal weight control subjects (see section 4.4). 

 

Pharmacokinetic interactions 

 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week subcutaneous toxicity studies both in rats and dogs and at 10 mg/kg/day in the 

26-week subcutaneous and intravenous toxicity studies both in rats, and monkeys. 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at subcutaneous doses of enoxaparin sodium up to 

30 mg/kg/day did not reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was 

found to have no effect on fertility or reproductive performance of male and female rats at subcutaneous 

doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Water for injections 

 

6.2 Incompatibilities 
 

Subcutaneous injection 

 

Do not mix with other products. 

 

Intravenous (Bolus) Injection (for acute STEMI indication only) 

 

Enoxaparin sodium may be safely administered with sodium chloride 9 mg/ml (0.9%) solution for injection 

or 5% dextrose in water (see section 4.2). 

 

6.3 Shelf life 

 

Pre-filled syringe 

 

2 years 

 

Diluted medicinal product with sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose 

 

8 hours 



 

151 

 

 

6.4 Special precautions for storage 

 

Store below 25 °C. Do not freeze. 

 

6.5 Nature and contents of container 

 

0.8 mL of solution in a clear, colourless type I neutral glass syringe barrel with fixed needle and needle 

shield closed by chlorobutyl rubber stopper and a purple polypropylene plunger rod. The syringe can be 

additionally equipped with needle guard. 

 

Packs of:  

- 2, 10 and 30 pre-filled syringes, 
- 10 and 30 pre-filled syringes with needle guard. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

INSTRUCTIONS FOR USE: PRE-FILLED SYRINGE  

 

How to give yourself an injection of Inhixa 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 



 

152 

 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin. 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold. 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has a needle guard attached to it in order to protect you from needle stick injury. 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 



 

153 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin. 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold. 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection. 

 



 

154 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Push hard the plunger. The needle guard, which is in the form of a plastic cylinder, will be activated 

automatically and it will completely cover the needle. 

 
10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/069 

EU/1/16/1132/073 

EU/1/16/1132/075 

EU/1/16/1132/076 

EU/1/16/1132/077 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 



 

155 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu.  

http://www.ema.europa.eu/


 

156 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 15,000 IU (150 mg)/1 mL solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each pre-filled syringe contains enoxaparin sodium 15,000 IU anti-Xa activity (equivalent to 150 mg) in 

1 mL water for injections. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerisation of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in pre-filled syringe. 

Clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in 
particular those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility 

at increased risk of venous thromboembolism.  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to 
require thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), 

in combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to 
be managed medically or with subsequent percutaneous coronary intervention (PCI). 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 

 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk 

surgery.  



 

157 

 

In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 

7-10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the 

patient no longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by subcutaneous injection preferably started 12 hours before surgery. If there 

is a need for earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high 

risk patient waiting for a deferred orthopaedic surgery), the last injection should be administered no 

later than 12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis 
up to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or 
pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by subcutaneous injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status 

(e.g. mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered subcutaneously either as a once daily injection of 150 IU/kg 

(1.5 mg/kg) or as twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by subcutaneous injection administered in combination with 

antiplatelet therapy. Treatment should be maintained for a minimum of 2 days and continued until 

clinical stabilization. The usual duration of treatment is 2 to 8 days.  

Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading 

dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75–325 mg/day 

long-term regardless of treatment strategy. 

 

 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) subcutaneous dose followed by 100 IU/kg 



 

158 

 

(1 mg/kg) administered subcutaneously every 12 hours (maximum 10,000 IU (100 mg) for each of the 

first two subcutaneous doses). Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg 

to 325 mg once daily) should be administered concomitantly unless contraindicated. The 

recommended duration of treatment is 8 days or until hospital discharge, whichever comes first. When 

administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific), enoxaparin 

sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic 

therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last subcutaneous dose of enoxaparin sodium was given 

less than 8 hours before balloon inflation, no additional dosing is needed. If the last 

subcutaneous administration was given more than 8 hours before balloon inflation, an 

intravenous bolus of 30 IU/kg (0.3 mg/kg) enoxaparin sodium should be administered. 

 

Special populations 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established. 

No data are available. 

 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below “renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥ 75 years of age, an initial intravenous bolus must not be 

used. Initiate dosing with 75 IU/kg (0.75 mg/kg) subcutaneous injection every 12 hours (maximum 7,500 IU 

(75 mg) for each of the first two subcutaneous doses only, followed by 75 IU/kg (0.75 mg/kg) subcutaneous 

dosing for the remaining doses). For dosage in elderly patients with impaired kidney function, see below 

“renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

Severe renal impairment  

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 

< 15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease 2,000 IU (20 mg) subcutaneously once daily 

Treatment of  DVT and PE 100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of acute STEMI (patients under 75) 

 

 

Treatment of acute STEMI (patients over 75) 

1 x 3,000 IU (30 mg) intravenous bolus plus 100 IU/kg 

(1 mg/kg) body weight subcutaneously and then 100 IU/kg 

(1 mg/kg) body weight subcutaneously every 24 hours 

No intravenous initial bolus, 100 IU/kg (1 mg/kg) body 

weight subcutaneously and then 100 IU/kg (1 mg/kg) body 

weight subcutaneously every 24 hours 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

Moderate and mild renal impairment 

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 

30-50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring 

is advised. 

 



 

159 

 

Method of administration  

 

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thrombo-embolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by subcutaneous 

injection. 

 For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately 
followed by a subcutaneous injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The pre-filled disposable syringe is ready for immediate use.  

 

The use of a tuberculin syringe or equivalent is recommended when using ampoules or multiple-dose vials to 

assure withdrawal of the appropriate volume of drug. 

 

Subcutaneous injection technique 

Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep subcutaneous injection.  

 

The air bubble should not be expelled from the syringe before the injection to avoid the loss of drug when 

using pre-filled syringes. When the quantity of drug to be injected requires to be adjusted based on the 

patient’s body weight, the graduated pre-filled syringes should be used to reach the required volume by 

discarding the excess before injection. In some cases it is not possible to achieve an exact dose due to the 

graduations on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. The injection 

site should not be rubbed after administration. 

 

Note for the pre-filled syringes fitted with an automatic safety system: The safety system is triggered at the 

end of the injection (see instructions in section 6.6). 

 

In case of self-administration, patient should be advised to follow instructions provided in the patient 

information leaflet included in the pack of this medicine. 

 

Intravenous (bolus) injection (for acute STEMI indication only) 

For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately followed 

by a subcutaneous injection.  

For intravenous injection, either the multidose vial or pre-filled syringe can be used. 

Enoxaparin sodium should be administered through an intravenous line. It should not be mixed or 

co-administered with other medications. To avoid the possible mixture of enoxaparin sodium with other 

drugs, the intravenous access chosen should be flushed with a sufficient amount of sodium chloride or 

dextrose solution prior to and following the intravenous bolus administration of enoxaparin sodium to clear 

the port of drug. Enoxaparin sodium may be safely administered with sodium chloride 9 mg/ml (0.9%) 

solution for injection or 5% dextrose in water. 

 

Initial 3,000 IU (30 mg) bolus 

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the intravenous line. 

 



 

160 

 

Additional bolus for PCI when last subcutaneous administration was given more than 8 hours before balloon 

inflation 

For patients being managed with PCI, an additional intravenous bolus of 30 IU/kg (0.3 mg/kg) is to be 

administered if last subcutaneous administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either sodium chloride 9 mg/ml (0.9%) solution for 

injection or 5% dextrose in water) as follows:  

30 mL of solution should be withdrawn from the infusion bag with a syringe and discarded. The complete 

contents of the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe should be injected into the 20 mL 

remaining in the bag. The contents of the bag should be gently mixed. Then, the required volume of diluted 

solution should be withdrawn with a syringe for administration into the intravenous line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 

Volume to be injected through intravenous line after dilution is completed at a concentration of 

300 IU (3 mg)/mL. 

 

Weight Required dose  

30 IU/kg (0.3 mg/kg) 

Volume to inject when diluted 

to a final concentration of  

300 IU (3 mg)/mL 

[kg] IU [mg] [mL] 

45 1350 13.5 4.5 

50 1500 15 5 

55 1650 16.5 5.5 

60 1800 18 6 

65 1950 19.5 6.5 

70 2100 21 7 

75 2250 22.5 7.5 

80 2400 24 8 

85 2550 25.5 8.5 

90 2700 27 9 

95 2850 28.5 9.5 

100 3000 30 10 

105 3150 31.5 10.5 

110 3300 33 11 

115 3450 34.5 11.5 

120 3600 36 12 

125 3750 37.5 12.5 

130 3900 39 13 

135 4050 40.5 13.5 

140 4200 42 14 

145 4350 43.5 14.5 

150 4500 45 15 

 

Arterial line injection 

It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 



 

161 

 

Switch between enoxaparin sodium and oral anticoagulants 

 

Switch between enoxaparin sodium and vitamin K antagonists (VKA)  

Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalized Ratio 

(INR)] must be intensified to monitor the effect of VKA. 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 

For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

 

At doses used for prophylaxis 

A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin sodium at 

prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with neuraxial 

anaesthesia. 

 

At doses used for treatment 

A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin sodium at 

curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg (1 mg/kg) 

twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay before catheter 

placement or removal.  

 

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH) or to any of the excipients listed in section 6.1; 



 

162 

 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

 

4.4 Special warnings and precautions for use 
 

General 

Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

History of HIT (> 100 days) 

Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (> 100 days) of 

heparin-induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in 

such a case must be made only after a careful benefit risk assessment and after non-heparin alternative 

treatments are considered (e.g. danaparoid sodium or lepirudin). 

 

Monitoring of platelet counts 

The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 

 

Haemorrhage 

As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 
- neuro- or ophthalmologic surgery, 
- concomitant use of medications affecting haemostasis (see section 4.5). 

 



 

163 

 

Laboratory tests 

At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

Spinal/Epidural anaesthesia or lumbar puncture 

Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 

To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach 

a sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance 

[15-30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is 

more prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

Skin necrosis / cutaneous vasculitis 

Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

Percutaneous coronary revascularization procedures 

To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last intravenous/subcutaneous enoxaparin sodium injection. If the 

treatment with enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 

6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or 

hematoma formation. 

 

Acute infective endocarditis 

Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after 

a careful individual benefit risk assessment. 

 



 

164 

 

Mechanical prosthetic heart valves 

The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 

Pregnant women with mechanical prosthetic heart valves 

The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

Elderly 

No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

Renal impairment 

In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which increases the 

risk of bleeding. In these patients, careful clinical monitoring is advised, and biological monitoring by 

anti-Xa activity measurement might be considered (see sections 4.2 and 5.2). 

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 

< 15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 

Hepatic impairment 

Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

Low weight 

An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (< 45 kg) and low-weight men (< 57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

Obese Patients 

Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI > 30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 

 

Hyperkalaemia 

Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  



 

165 

 

Traceability 

LMWHs are biological medicinal products. In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded. 

  

Sodium content 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended  

 

Medicinal products affecting haemostasis (see section 4.4) 

It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 

 

Concomitant use with caution 

 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  
- Systemic glucocorticoids. 

 

Medicinal products increasing potassium levels 

Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 



 

166 

 

Breast-feeding  

 

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely. Inhixa can be used during breastfeeding. 

 

Fertility 

 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) subcutaneously once daily for prophylaxis of deep vein 

thrombosis following surgery or in acutely ill medical patients with severely restricted mobility. In treatment 

of DVT with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg 

(1 mg/kg) subcutaneous dose every 12 hours or a 150 IU/kg (1.5 mg/kg) subcutaneous dose once a day. In 

the clinical studies for treatment of unstable angina and non-Q-wave myocardial infarction, doses were 

100 IU/kg (1 mg/kg) subcutaneously every 12 hours, and in the clinical study for treatment of acute STEMI 

enoxaparin sodium regimen was a 3,000 IU (30 mg) intravenous bolus followed by 100 IU/kg (1 mg/kg) 

subcutaneously every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see section 4.4 and 'Description of selected adverse reactions' below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 

(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

 Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 

 Rare: Eosinophilia* 

 Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 
complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

 Common: Allergic reaction 



 

167 

 

 Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

 Common: Headache* 
 

Vascular disorders 

 Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees 
of neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 

 Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of 
normality) 

 Uncommon: Hepatocellular liver injury*  

 Rare: Cholestatic liver injury* 
 

Skin and subcutaneous tissue disorders 

 Common: Urticaria, pruritus, erythema  

 Uncommon: Bullous dermatitis 

 Rare: Alopecia* 

 Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena 
have been usually preceded by purpura or erythematous plaques, infiltrated and painful). 

 Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 
resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

 Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 

General disorders and administration site conditions 

 Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

 Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

 Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting 

haemostasis (see sections 4.4 and 4.5). 



 

168 

 

System Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical 

patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood and 

lymphatic 

system 

disorders 

Very common: 

Haemorrhage 
α
 

 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
  

Very common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage 
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and 

gastro-intestinal haemorrhage. 

 

Thrombocytopenia and thrombocytosis 

System Organ 

Class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical 

patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood and 

lymphatic 

system 

disorders 

Very common: 

Thrombocytosis
β
 

 

 

Common: 

Thrombo-

cytopenia 

Uncommon: 

Thrombo-

cytopenia 

 

Very common:    

Thrombo-

cytosis
β
 

 

Common: 

Thrombo-

cytopenia 

Uncommon: 

Thrombo-

cytopenia 

Common:  

Thrombocytosis
β
 

Thrombo-

cytopenia 

Very rare:     

Immuno-allergic 

thrombo-

cytopenia 
β
: Platelet increased > 400 G/L  

 

Paediatric population 

 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

 

Accidental overdose with enoxaparin sodium after intravenous, extracorporeal or subcutaneous 

administration may lead to haemorrhagic complications. Following oral administration of even large doses, it 

is unlikely that enoxaparin sodium will be absorbed. 

 

Management 

 

The anticoagulant effects can be largely neutralized by the slow intravenous injection of protamine. The dose 

of protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the 

anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the 

previous 8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be 

administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine 

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169 

 

administration, or if it has been determined that a second dose of protamine is required. After 12 hours of the 

enoxaparin sodium injection, protamine administration may not be required. However, even with high doses 

of protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 

60%) (see the prescribing information for protamine salts). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

Pharmacodynamic effects 

 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

Extended prophylaxis of VTE following orthopaedic surgery  

In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 

179 patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin 

sodium 4,000 IU (40 mg) subcutaneously, were randomized to a post-discharge regimen of either enoxaparin 

sodium 4,000 IU (40 mg) (n = 90) once a day subcutaneously or to placebo (n = 89) for 3 weeks. The 

incidence of DVT during extended prophylaxis was significantly lower for enoxaparin sodium compared to 

placebo, no PE was reported. No major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) once a day 

subcutaneously 

n (%) 

Placebo  

once a day 

subcutaneously 

n (%) 

All Treated Extended Prophylaxis Patients 90 (100) 89 (100) 

Total VTE 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)*  18 (20.2) 

 Proximal DVT (%) 5 (5.6)
# 
 7 (8.8) 

*p value versus placebo = 0.008 

#p value versus placebo = 0.537 

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170 

 

 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) subcutaneously were 

randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n = 131) once a day 

subcutaneously or to placebo (n = 131) for 3 weeks. Similar to the first study the incidence of VTE during 

extended prophylaxis was significantly lower for enoxaparin sodium compared to placebo for both total VTE 

(enoxaparin sodium 21 [16%] versus placebo 45 [34.4%]; p = 0.001) and proximal DVT (enoxaparin sodium 

8 [6.1%] versus placebo 28 [21.4%]; p =< 0.001). No difference in major bleeding was found between the 

enoxaparin sodium and the placebo group. 

 

Extended prophylaxis of DVT following cancer surgery 

A double-blind, multicentre trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) subcutaneously) daily for 6 to 10 days 

and were then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. 

Bilateral venography was performed between days 25 and 31, or sooner if symptoms of venous 

thromboembolism occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis 

for four weeks after surgery for abdominal or pelvic cancer significantly reduced the incidence of 

venographically demonstrated thrombosis, as compared with enoxaparin sodium prophylaxis for one week. 

The rates of venous thromboembolism at the end of the double-blind phase were 12.0 % (n = 20) in the 

placebo group and 4.8% (n = 8) in the enoxaparin sodium group; p = 0.02. This difference persisted at three 

months [13.8% vs. 5.5% (n = 23 vs 9), p = 0.01]. There were no differences in the rates of bleeding or other 

complications during the double-blind or follow-up periods. 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicentre, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day subcutaneously was compared to placebo in the prophylaxis of DVT in medical patients 

with severely restricted mobility during acute illness (defined as walking distance of < 10 meters for 

≤ 3 days). This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

least one VTE risk factor (age ≥ 75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day subcutaneously, 

enoxaparin sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are 

provided in the table below. 

 

 Enoxaparin sodium  

2,000 IU (20 mg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg) 

once a day 

subcutaneously 

n (%) 

Placebo  

 

 

n (%) 

All Treated Medical Patients 

During Acute Illness 

287 (100) 291 (100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5)  40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 
VTE = Venous thromboembolic events which included DVT, PE, and death considered to be thromboembolic in origin 

* p value versus placebo = 0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 



 

171 

 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicentre, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day subcutaneously, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours subcutaneously, 

or (iii) heparin intravenous bolus (5,000 IU) followed by a continuous infusion (administered to achieve an 

aPTT of 55 to 85 seconds). A total of 900 patients were randomized in the study and all patients were 

treated. All patients also received warfarin sodium (dose adjusted according to prothrombin time to achieve 

an INR of 2.0 to 3.0), commencing within 72 hours of initiation of enoxaparin sodium or standard heparin 

therapy, and continuing for 90 days. Enoxaparin sodium or standard heparin therapy was administered for a 

minimum of 5 days and until the targeted warfarin sodium INR was achieved.  Both enoxaparin sodium 

regimens were equivalent to standard heparin therapy in reducing the risk of recurrent venous 

thromboembolism (DVT and/or PE). The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  
150 IU/kg (1.5 mg/kg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

100 IU/kg (1 mg/kg) 

twice a day 

subcutaneously 

n (%) 

Heparin  

aPTT Adjusted 

Intravenous Therapy 

n (%) 

All Treated DVT Patients 

with or without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

 DVT Only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

 Proximal DVT (%) 9 (3.0) 6 (1.9) 7 (2.4) 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 
VTE = venous thromboembolic event (DVT and/or PE) 

*The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  

- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicentre study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either subcutaneous enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or intravenous 

unfractionated heparin adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 

2 days and a maximum of 8 days, until clinical stabilization, revascularization procedures or hospital 

discharge. The patients had to be followed up to 30 days. In comparison with heparin, enoxaparin sodium 

significantly reduced the combined incidence of angina pectoris, myocardial infarction and death, with a 

decrease of 19.8 to 16.6% (relative risk reduction of 16.2%) on day 14. This reduction in the combined 

incidence was maintained after 30 days (from 23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the 

subcutaneous injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicentre study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) intravenous bolus plus 

a 100 IU/kg (1 mg/kg) subcutaneous dose followed by an subcutaneous injection of 100 IU/kg (1 mg/kg) 

every 12 hours or intravenous unfractionated heparin adjusted based on aPTT for 48 hours. All patients were 

also treated with acetylsalicylic acid for a minimum of 30 days. The enoxaparin sodium dosing strategy was 

adjusted for severe renally impaired patients and for the elderly of at least 75 years of age. The subcutaneous 

injections of enoxaparin sodium were given until hospital discharge or for a maximum of eight days 

(whichever came first). 

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172 

 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last 

subcutaneous administration given less than 8 hours before balloon inflation, intravenous bolus of 30 IU/ kg 

(0.3 mg/kg) enoxaparin sodium, if the last subcutaneous administration given more than 8 hours before 

balloon inflation. 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p < 0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p < 0.001). 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p = 0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage 

(a measure of net clinical benefit) was significantly lower (p < 0.0001) in the enoxaparin sodium group 

(10.1%) as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of 

treatment with enoxaparin sodium. 

The incidence of major bleeding at 30 days was significantly higher (p < 0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated subcutaneous administration and after single intravenous administration. The quantitative 

determination of anti-Xa and anti-IIa pharmacokinetic activities was conducted by validated amidolytic 

methods. 

 

Absorption 

 

The absolute bioavailability of enoxaparin sodium after subcutaneous injection, based on anti-Xa activity, is 

close to 100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after subcutaneous injection and 

achieves approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single subcutaneous administration of 

2,000 IU, 4,000 IU, 100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 



 

173 

 

 

A 3,000 IU (30 mg) intravenous bolus immediately followed by a 100 IU/kg (1 mg/kg) subcutaneously every 

12 hours provided initial maximum anti-Xa activity level of 1.16 IU/mL (n = 16) and average exposure 

corresponding to 88% of steady-state levels. Steady-state is achieved on the second day of treatment. 

 

After repeated subcutaneous administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once 

daily regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio 

about 15% higher than after a single dose. After repeated subcutaneous administration of the 100 IU/kg 

(1 mg/kg) twice daily regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% 

higher than after a single dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 

0.52 IU/mL, respectively.  

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated subcutaneous administration no 

accumulation takes place. 

 

Plasma anti-IIa activity after subcutaneous administration is approximately ten-fold lower than anti-Xa 

activity. The mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following 

subcutaneous injection and reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 

100 IU/kg (1 mg/kg) twice daily and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 

 

Biotransformation 

 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerisation to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour intravenous infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single subcutaneous dose to about 

7 hours after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal.  However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 



 

174 

 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine 

clearance < 30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) intravenous dose however, AUC was two-fold higher than control. 

 

Weight 

After repeated subcutaneous 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is 

marginally higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese 

control subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-

adjusted clearance in obese subjects with subcutaneous dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single- subcutaneous 4,000 IU 

(40 mg) dose, that anti-Xa exposure is 52% higher in low-weight women (< 45 kg) and 27% higher in 

low-weight men (< 57 kg) when compared to normal weight control subjects (see section 4.4). 

 

Pharmacokinetic interactions 

 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week subcutaneous toxicity studies both in rats and dogs and at 10 mg/kg/day in the 

26-week subcutaneous and intravenous toxicity studies both in rats, and monkeys. 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at subcutaneous doses of enoxaparin sodium up to 

30 mg/kg/day did not reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was 

found to have no effect on fertility or reproductive performance of male and female rats at subcutaneous 

doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Water for injections 

 

6.2 Incompatibilities 
 

Subcutaneous injection 

 

Do not mix with other products. 

 

Intravenous (Bolus) Injection (for acute STEMI indication only) 

 



 

175 

 

Enoxaparin sodium may be safely administered with sodium chloride 9 mg/ml (0.9%) solution for injection 

or 5% dextrose in water (see section 4.2). 

 

6.3 Shelf life 

 

Pre-filled syringe 

 

2 years 

 

Diluted medicinal product with sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose 

 

8 hours 

 

6.4 Special precautions for storage 

 

Store below 25 °C. Do not freeze. 

 

6.5 Nature and contents of container 

 

1 mL of solution in a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield 

closed by chlorobutyl rubber stopper and a dark blue polypropylene plunger rod. The syringe can be 

additionally equipped with needle guard. 

 

Packs of:  

- 2, 10 and 30 pre-filled syringes, 
- 10 and 30 pre-filled syringes with a needle guard. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

INSTRUCTIONS FOR USE: PRE-FILLED SYRINGE  

 

How to give yourself an injection of Inhixa 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 



 

176 

 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin. 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold. 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection. 

 

8)  Remove the needle by pulling it straight out. 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 



 

177 

 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has a needle guard attached to it in order to protect you from needle stick injury. 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin. 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold. 

 



 

178 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Push hard the plunger. The needle guard, which is in the form of a plastic cylinder, will be activated 

automatically and it will completely cover the needle. 

 
10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/070 

EU/1/16/1132/074 



 

179 

 

EU/1/16/1132/078 

EU/1/16/1132/079 

EU/1/16/1132/080 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


 

180 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 30,000 IU (300 mg)/3 mL solution for injection in multidose vial 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One vial contains enoxaparin sodium 30,000 IU anti-Xa activity (equivalent to 300 mg) in 3.0 mL water for 

injections. 

 

Each mL contains 10,000 IU (100 mg) enoxaparin sodium. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerisation of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

Excipient(s) with known effect 

 

Benzyl alcohol (45 mg in 3.0 mL) 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in multidose vial 

Clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in 
particular those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility 

at increased risk of venous thromboembolism (VTE).  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to 
require thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), 

in combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to 
be managed medically or with subsequent percutaneous coronary intervention (PCI). 

 



 

181 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 

 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk 

surgery.  

In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 

7-10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the 

patient no longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by subcutaneous injection preferably started 12 hours before surgery. If there 

is a need for earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high 

risk patient waiting for a deferred orthopaedic surgery), the last injection should be administered no 

later than 12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis up 
to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or 
pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by subcutaneous injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status 

(e.g. mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered subcutaneously either as a once daily injection of 150 IU/kg (1.5 

mg/kg) or as twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 



 

182 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by subcutaneous injection administered in combination with 

antiplatelet therapy. Treatment should be maintained for a minimum of 2 days and continued until 

clinical stabilization. The usual duration of treatment is 2 to 8 days.  

Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading 

dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75-325 mg/day 

long-term regardless of treatment strategy. 

 

 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) subcutaneous dose followed by 100 IU/kg 

(1 mg/kg) administered subcutaneously every 12 hours (maximum 10,000 IU (100 mg) for each of the 

first two subcutaneous doses). Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg 

to 325 mg once daily) should be administered concomitantly unless contraindicated. The 

recommended duration of treatment is 8 days or until hospital discharge, whichever comes first. When 

administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific), enoxaparin 

sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic 

therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last subcutaneous dose of enoxaparin sodium was given 

less than 8 hours before balloon inflation, no additional dosing is needed. If the last 

subcutaneous administration was given more than 8 hours before balloon inflation, an 

intravenous bolus of 30 IU/kg (0.3 mg/kg) enoxaparin sodium should be administered. 

 

Special populations 

 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below paragraph “Renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥75 years of age, an initial intravenous bolus must not be 

used. Initiate dosing with 75 IU/kg (0.75 mg/kg) subcutaneously every 12 hours (maximum 7,500 IU 

(75 mg) for each of the first two subcutaneous doses only, followed by 75 IU/kg (0.75 mg/kg) subcutaneous 

dosing for the remaining doses). For dosage in elderly patients with impaired kidney function, see below 

“renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

Severe renal impairment  

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 

<15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease 2,000 IU (20 mg) subcutaneously once daily 

Treatment of DVT and PE 100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of acute STEMI (patients under 75) 

 

1 x 3,000 IU (30 mg) intravenous bolus plus 100 IU/kg 

(1 mg/kg) body weight subcutaneously and then 100 IU/kg 



 

183 

 

 

Treatment of acute STEMI (patients over 75) 

(1 mg/kg) body weight subcutaneously every 24 hours 

No intravenous initial bolus, 100 IU/kg (1 mg/kg) body 

weight subcutaneously and then 100 IU/kg (1 mg/kg) body 

weight subcutaneously every 24 hours 

 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

Moderate and mild renal impairment 

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 

30-50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring 

is advised. 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established. 

No data are available. 

 

Inhixa multidose vial contains benzyl alcohol and must not be used in newborn and premature neonates 

(see section 4.3). 

 

Method of administration  

 

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thromboembolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by subcutaneous 

injection. 

 For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately 
followed by a subcutaneous injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The use of a tuberculin syringe or equivalent is recommended when using multiple-dose vials to assure 

withdrawal of the appropriate volume of drug. 

 

Subcutaneous injection technique 

Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep subcutaneous injection.  

 

The air bubble should not be expelled from the syringe before the injection to avoid the loss of drug when 

using pre-filled syringes. When the quantity of drug to be injected requires to be adjusted based on the 

patient’s body weight, the graduated pre-filled syringes should be use to reach the required volume by 

discarding the excess before injection. In some cases it is not possible to achieve an exact dose due to the 

graduations on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. The injection 

site should not be rubbed after administration. 

 

Intravenous (bolus) injection (for acute STEMI indication only) 

For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately followed 

by a subcutaneous injection.  

For intravenous injection, either the multidose vial or pre-filled syringe can be used. 



 

184 

 

Enoxaparin sodium should be administered through an intravenous line. It should not be mixed or co-

administered with other medicinal products. To avoid the possible mixture of enoxaparin sodium with other 

drugs, the intravenous access chosen should be flushed with a sufficient amount of sodium chloride 9 mg/mL 

(0.9%) solution for infusion or glucose solution prior to and following the intravenous bolus administration 

of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely administered with sodium 

chloride 9 mg/mL (0.9%) solution for infusion or 5% glucose in water for injections. 

 

Initial 3,000 IU (30 mg) bolus 

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the intravenous line. 

 

Additional bolus for PCI when last subcutaneous administration was given more than 8 hours before balloon 

inflation 

For patients being managed with PCI, an additional intravenous bolus of 30 IU/kg (0.3 mg/kg) is to be 

administered if last subcutaneous administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either normal sodium chloride 9 mg/mL (0.9%) 

solution for infusion or 5% glucose in water for injections) as follows:  

30 mL of the solution should be withdrawn from the infusion bag with a syringe and discarded. The 

complete contents of the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe should be injected into the 

20 mL remaining in the bag. The contents of the bag should be gently mixed. Then, the required volume of 

diluted solution should be withdrawn with a syringe for administration into the intravenous line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 

Volume to be injected through intravenous line after dilution is completed at a concentration of 300 IU 

(3 mg)/mL. 

 

Weight 
Required dose 

30 IU/kg (0.3 mg/kg) 

Volume to inject when diluted to a final 

concentration of 300 IU (3 mg)/mL 

[kg] IU [mg] [mL] 

45 1,350 13.5 4.5 

50 1,500 15 5 

55 1,650 16.5 5.5 

60 1,800 18 6 

65 1,950 19.5 6.5 

70 2,100 21 7 

75 2,250 22.5 7.5 

80 2,400 24 8 

85 2,550 25.5 8.5 

90 2,700 27 9 

95 2,850 28.5 9.5 

100 3,000 30 10 

105 3,150 31.5 10.5 

110 3,300 33 11 

115 3,450 34.5 11.5 

120 3,600 36 12 

125 3,750 37.5 12.5 

130 3,900 39 13 

135 4,050 40.5 13.5 



 

185 

 

140 4,200 42 14 

145 4,350 43.5 14.5 

150 4,500 45 15 

 

Arterial line injection 

It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 

Switch between enoxaparin sodium and oral anticoagulants 

Switch between enoxaparin sodium and vitamin K antagonists (VKA)  

Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalised Ratio 

(INR)] must be intensified to monitor the effect of VKA. 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 

For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

 

At doses used for prophylaxis 

A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin sodium at 

prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with neuraxial 

anaesthesia. 

 

At doses used for treatment 

A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin sodium at 

curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg (1 mg/kg) 

twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay before catheter 

placement or removal.  

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 



 

186 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH), to benzyl alcohol or any other of the excipients listed in section 6.1; 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

Because of the content of benzyl alcohol (see section 6.1), enoxaparin sodium multiple dose vial formulation 

must not be given to newborns or premature neonates (see sections 4.4 and 4.6). 

 

4.4 Special warnings and precautions for use 
 

General 

 

Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

History of HIT (>100 days) 

 

Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-

induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such 

a case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments 

are considered (e.g. danaparoid sodium or lepirudin). 

 

Monitoring of platelet counts 

 

The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 

 

Haemorrhage 

 

As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  



 

187 

 

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 
- neuro- or ophthalmologic surgery, 
- concomitant use of medicinal products affecting haemostasis (see section 4.5). 

 

Laboratory tests 

 

At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

Spinal/Epidural anaesthesia or lumbar puncture 

 

Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 

To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach 

a sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance 

[15-30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is 

more prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

Skin necrosis / cutaneous vasculitis 

 

Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

Percutaneous coronary revascularization procedures 

 

To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 



 

188 

 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last intravenous/ subcutaneous enoxaparin sodium injection. If the 

treatment with enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 

6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or 

hematoma formation. 

 

Acute infective endocarditis 

 

Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after 

a careful individual benefit risk assessment. 

 

Mechanical prosthetic heart valves 

 

The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 

Pregnant women with mechanical prosthetic heart valves 

The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg ) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

Elderly 

 

No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

Renal impairment 

 

 In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which 
increases the risk of bleeding. In these patients, careful clinical monitoring is advised, and biological 

monitoring by anti-Xa activity measurement might be considered (see sections 4.2 and 5.2). 

 Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 
<15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in 

extra corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 



 

189 

 

Hepatic impairment 

 

Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

Low weight 

 

An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

Obese Patients 

 

Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI >30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 

 

Hyperkalaemia 

 

Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  

Traceability 

 

LMWHs are biological medicinal products. In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded. 

  

Benzyl alcohol 

 

Benzyl alcohol may cause allergic reactions. 

Intravenous administration of benzyl alcohol has been associated with serious adverse events and death in 

neonates (“Gasping Syndrome”) (see section 4.3). The minimum amount of benzyl alcohol at which toxicity 

may occur is not known. Benzyl alcohol may also cause toxic reactions in infants and children up to 3 years 

old, due to increased risk of accumulation. 

High volumes of medicinal products containing benzyl alcohol should be used with caution and only if 

necessary in patients with liver or kidney impairment, or in pregnant women, because of the risk of 

accumulation of benzyl alcohol and its toxicity (metabolic acidosis). 

 

Sodium 

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose within the recommended dose 

range, that is to say essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended 

 

Medicinal products affecting haemostasis (see section 4.4) 

It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 



 

190 

 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 

 

Concomitant use with caution 

 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  
- Systemic glucocorticoids. 

 

Medicinal products increasing potassium levels 

Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 

As benzyl alcohol may cross the placenta, it is recommended to use a formulation that does not contain 

benzyl alcohol. 

 

Breast-feeding  

 

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely. Inhixa can be used during breastfeeding. 

 

Fertility 

 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 



 

191 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) subcutaneously once daily for prophylaxis of deep vein 

thrombosis following surgery or in acutely ill medical patients with severely restricted mobility. In treatment 

of DVT with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg 

(1 mg/kg) subcutaneous dose every 12 hours or a 150 IU/kg (1.5 mg/kg) subcutaneous dose once a day. In 

the clinical studies for treatment of unstable angina and non-Q-wave myocardial infarction, doses were 

100 IU/kg (1 mg/kg) subcutaneously every 12 hours, and in the clinical study for treatment of acute STEMI 

enoxaparin sodium regimen was a 3,000 IU (30 mg) intravenous bolus followed by 100 IU/kg (1 mg/kg) 

subcutaneously every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see sections 4.4 and ”Description of selected adverse reactions” below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 

(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

 Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 

 Rare: Eosinophilia* 

 Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 
complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

 Common: Allergic reaction 

 Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

 Common: Headache* 
 

Vascular disorders 

 Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees 
of neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 

 Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of 
normality) 

 Uncommon: Hepatocellular liver injury *  

 Rare: Cholestatic liver injury* 
 



 

192 

 

Skin and subcutaneous tissue disorders 

 Common: Urticaria, pruritus, erythema  

 Uncommon: Bullous dermatitis 

 Rare: Alopecia* 

 Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena 
have been usually preceded by purpura or erythematous plaques, infiltrated and painful). 

Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 

resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

 Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 

General disorders and administration site conditions 

 Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

 Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

 Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medicinal products affecting 

haemostasis (see sections 4.4 and 4.5). 

 

System 

organ 

class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymphatic 

system 

disorders 

Very common: 

Haemorrhage
α
 

 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage
α
  

Very common: 

Haemorrhage
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage
α
 

 

Rare: 

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and gastro-intestinal 

haemorrhage. 

 



 

193 

 

Thrombocytopenia and thrombocytosis 

System 

organ 

class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymphatic 

system 

disorders 

Very common: 

Thrombo- 

cytosis
β
 

 

Common: 

Thrombo- 

cytopenia 

Uncommon: 

Thrombo-

cytopenia 

Very common: 

Thrombo-

cytosis
β
 

 

Common: 

Thrombo-

cytopenia 

Uncommon: 

Thrombo-

cytopenia 

Common: 

Thrombocytosis
β
 

Thrombo-

cytopenia 

Very rare: 

Immuno-allergic 

thrombo-

cytopenia 
β
: Platelet increased >400 G/L  

 

Paediatric population 

 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Intravenous administration of benzyl alcohol has been associated with serious adverse events and death in 

neonates (“Gasping Syndrome”) (see section 4.3). 

Benzyl alcohol may also cause toxic reactions in infants and children up to 3 years old, due to increased risk 

of accumulation (see section 4.4). 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

 

Accidental overdose with enoxaparin sodium after intravenous, extracorporeal or subcutaneous 

administration may lead to haemorrhagic complications. Following oral administration of even large doses, it 

is unlikely that enoxaparin sodium will be absorbed. 

 

Management 

 

The anticoagulant effects can be largely neutralized by the slow intravenous injection of protamine. The dose 

of protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the 

anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the 

previous 8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be 

administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine 

administration, or if it has been determined that a second dose of protamine is required. After 12 hours of the 

enoxaparin sodium injection, protamine administration may not be required. However, even with high doses 

of protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 

60%) (see the prescribing information for protamine salts). 

 

 

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194 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

Pharmacodynamic effects 

 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

Extended prophylaxis of VTE following orthopaedic surgery  

In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 

179 patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin 

sodium 4,000 IU (40 mg) subcutaneously, were randomized to a post-discharge regimen of either enoxaparin 

sodium 4,000 IU (40 mg) (n=90) once a day subcutaneously or to placebo (n=89) for 3 weeks. The incidence 

of DVT during extended prophylaxis was significantly lower for enoxaparin sodium compared to placebo, no 

PE was reported. No major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) once a day 

subcutaneously 

n (%) 

Placebo  

once a day subcutaneously 

n (%) 

All treated extended prophylaxis patients 90 (100) 89 (100) 

Total VTE (%) 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)* 18 (20.2) 

 Proximal DVT (%) 5 (5.6)
#
 7 (8.8) 

*p value versus placebo =0.008 

#p value versus placebo =0.537 
 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) subcutaneously were 

randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n=131) once a day 

subcutaneously or to placebo (n=131) for 3 weeks. Similar to the first study the incidence of VTE during 

extended prophylaxis was significantly lower for enoxaparin sodium compared to placebo for both total VTE 

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195 

 

(enoxaparin sodium 21 [16%] versus placebo 45 [34.4%]; p=0.001) and proximal DVT (enoxaparin sodium 

8 [6.1%] versus placebo 28 [21.4%]; p=<0.001). No difference in major bleeding was found between the 

enoxaparin sodium and the placebo group. 

 

Extended prophylaxis of DVT following cancer surgery 

A double-blind, multicentre trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) subcutaneously) daily for 6 to 10 days 

and were then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. 

Bilateral venography was performed between days 25 and 31, or sooner if symptoms of venous 

thromboembolism occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis 

for four weeks after surgery for abdominal or pelvic cancer significantly reduced the incidence of 

venographically demonstrated thrombosis, as compared with enoxaparin sodium prophylaxis for one week. 

The rates of venous thromboembolism at the end of the double-blind phase were 12.0 % (n=20) in the 

placebo group and 4.8% (n=8) in the enoxaparin sodium group; p=0.02. This difference persisted at three 

months [13.8% vs. 5.5% (n=23 vs 9), p=0.01]. There were no differences in the rates of bleeding or other 

complications during the double-blind or follow-up periods. 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicentre, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day subcutaneously was compared to placebo in the prophylaxis of DVT in medical patients 

with severely restricted mobility during acute illness (defined as walking distance of <10 meters for 

≤3 days). This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

least one VTE risk factor (age ≥75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day subcutaneously, 

enoxaparin sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are 

provided in the table below. 

 

 Enoxaparin sodium  

2,000 IU (20 mg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg)  

once a day 

subcutaneously 

n (%) 

Placebo  

n (%) 

All treated medical patients 

during acute illness 

287 (100) 291(100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5) 40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 
VTE = Venous thromboembolic events which included DVT, PE, and death considered to be thromboembolic in origin 

* p value versus placebo = 0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicentre, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day subcutaneously, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours subcutaneously, or 

(iii) heparin intravenous bolus (5,000 IU) followed by a continuous infusion (administered to achieve an 



 

196 

 

aPTT of 55 to 85 seconds). A total of 900 patients were randomized in the study and all patients were 

treated. All patients also received warfarin sodium (dose adjusted according to prothrombin time to achieve 

an INR of 2.0 to 3.0), commencing within 72 hours of initiation of enoxaparin sodium or standard heparin 

therapy, and continuing for 90 days. Enoxaparin sodium or standard heparin therapy was administered for a 

minimum of 5 days and until the targeted warfarin sodium INR was achieved. Both enoxaparin sodium 

regimens were equivalent to standard heparin therapy in reducing the risk of recurrent venous 

thromboembolism (DVT and/or PE). The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

150 IU/kg (1.5 mg/kg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

100 IU/kg (1 mg/kg) 

twice a day 

subcutaneously 

n (%) 

Heparin  

aPTT Adjusted Intravenous 

Therapy 

n (%) 

All treated DVT patients 

with or without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

 DVT only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

 Proximal DVT (%) 9 (3.0) 6 (1.9) 7 (2.4) 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 

VTE = venous thromboembolic event (DVT and/or PE) 

* The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  
- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicentre study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either subcutaneous enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or intravenous 

unfractionated heparin adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 

2 days and a maximum of 8 days, until clinical stabilization, revascularization procedures or hospital 

discharge. The patients had to be followed up to 30 days. In comparison with heparin, enoxaparin sodium 

significantly reduced the combined incidence of angina pectoris, myocardial infarction and death, with a 

decrease of 19.8 to 16.6% (relative risk reduction of 16.2%) on day 14. This reduction in the combined 

incidence was maintained after 30 days (from 23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the 

subcutaneous injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicentre study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) intravenous bolus plus 

a 100 IU/kg (1 mg/kg) subcutaneously dose followed by an subcutaneous injection of 100 IU/kg (1 mg/kg) 

every 12 hours or intravenous unfractionated heparin adjusted based on aPTT for 48 hours. All patients were 

also treated with acetylsalicylic acid for a minimum of 30 days. The enoxaparin sodium dosing strategy was 

adjusted for severe renally impaired patients and for the elderly of at least 75 years of age. The subcutaneous 

injections of enoxaparin sodium were given until hospital discharge or for a maximum of eight days 

(whichever came first). 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last 

subcutaneous administration given less than 8 hours before balloon inflation, intravenous bolus of 30 IU/ kg 

(0.3 mg/kg) enoxaparin sodium, if the last subcutaneous administration given more than 8 hours before 

balloon inflation. 

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197 

 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p<0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p<0.001). 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p=0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage 

(a measure of net clinical benefit) was significantly lower (p<0.0001) in the enoxaparin sodium group 

(10.1%) as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of 

treatment with enoxaparin sodium. 

The incidence of major bleeding at 30 days was significantly higher (p<0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated subcutaneous administration and after single intravenous administration. The quantitative 

determination of anti-Xa and anti-IIa pharmacokinetic activities was conducted by validated amidolytic 

methods. 

 

Absorption 

 

The absolute bioavailability of enoxaparin sodium after subcutaneous injection, based on anti-Xa activity, is 

close to 100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after subcutaneous injection and 

achieves approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single subcutaneous administration of 

2,000 IU, 4,000 IU, 100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 

 

A 3,000 IU (30 mg) intravenous bolus immediately followed by a 100 IU/kg (1 mg/kg) subcutaneous every 

12 hours provided initial maximum anti-Xa activity level of 1.16 IU/mL (n=16) and average exposure 

corresponding to 88% of steady-state levels. Steady-state is achieved on the second day of treatment. 

 



 

198 

 

After repeated subcutaneous administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once 

daily regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio 

about 15% higher than after a single dose. After repeated subcutaneous administration of the 100 IU/kg 

(1 mg/kg) twice daily regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% 

higher than after a single dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 

0.52 IU/mL, respectively.  

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated subcutaneous administration no 

accumulation takes place. 

 

Plasma anti-IIa activity after subcutaneous administration is approximately ten-fold lower than anti-Xa 

activity. The mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following 

subcutaneous injection and reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 

100 IU/kg (1 mg/kg) twice daily and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 

 

Biotransformation 

 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerisation to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour intravenous infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single subcutaneous dose to about 

7 hours after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal.  However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine 



 

199 

 

clearance <30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) intravenous dose however, AUC was two-fold higher than control. 

 

Weight 

After repeated subcutaneous 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is 

marginally higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese 

control subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-

adjusted clearance in obese subjects with subcutaneous dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single- subcutaneous 4,000 IU 

(40 mg) dose, that anti-Xa exposure is 52% higher in low-weight women (<45 kg) and 27% higher in low-

weight men (<57 kg) when compared to normal weight control subjects (see section 4.4). 

 

Pharmacokinetic interactions 

 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week subcutaneous toxicity studies both in rats and dogs and at  10 mg/kg/day in the 

26-week subcutaneous and intravenous toxicity studies both in rats, and monkeys. 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at subcutaneous doses of enoxaparin sodium up to 

30 mg/kg/day did not reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was 

found to have no effect on fertility or reproductive performance of male and female rats at subcutaneous 

doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Benzyl alcohol  

Water for injections 

 

6.2 Incompatibilities 
 

Subcutaneous injection 

 

Do not mix with other medicinal products. 

 

Intravenous (Bolus) injection (for acute STEMI indication only)  

 

This medicinal product must not be mixed with other medicinal products except those mentioned in section 

6.6. 

 

6.3 Shelf life 



 

200 

 

 

3 years 

 

After first opening 

 

Chemical and physical in-use stability has been demonstrated for 28 days at 25°C.  

From a microbiological point of view, once opened, the product may be stored for a maximum of 28 days 

below 25°C. Other in-use storage times and conditions are the responsibility of the user. 

 

After dilution with sodium chloride 9 mg/ml (0.9%) solution for infusion or 5% glucose solution for 

injection. 

 

Chemical and physical in-use stability has been demonstrated for 8 hours at 25°C.  

From a microbiological point of view, unless the method of dilution precludes the risk of microbial 

contamination, the product should be used immediately. If not used immediately, in-use storage times and 

conditions are the responsibility of user. 

 

6.4 Special precautions for storage 

 

Store below 25°C. Do not freeze. 

For storage conditions after first opening and dilution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

3 mL of solution in clear, colourless type I glass vial sealed with rubber injection stopper and white 

aluminium-plastic cap in a cardboard box. 

 

Pack-sizes of 1 vial containing 3 mL. 

 

6.6 Special precautions for disposal and other handling 
 

Enoxaparin sodium may be safely administered with sodium chloride 9 mg/ml (0.9%) solution for infusion 

or 5% glucose solution for injection (see section 4.2). 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/071 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 



 

201 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


 

202 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 50,000 IU (500 mg)/5 mL solution for injection in multidose vial 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One vial contains enoxaparin sodium 50,000 IU anti-Xa activity (equivalent to 500 mg) in 5.0 mL water for 

injections. 

 

Each mL contains 10,000 IU (100 mg) enoxaparin sodium. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerisation of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

Excipient(s) with known effect 

 

Benzyl alcohol (75 mg in 5.0 mL) 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in multidose vial 

Clear, colourless to pale yellow solution 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in 
particular those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility 

at increased risk of venous thromboembolism (VTE).  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to 
require thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), 

in combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to 
be managed medically or with subsequent percutaneous coronary intervention (PCI). 

 



 

203 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 

 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk 

surgery.  

 In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 
7-10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the 

patient no longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by subcutaneous injection preferably started 12 hours before surgery. If there 

is a need for earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high 

risk patient waiting for a deferred orthopaedic surgery), the last injection should be administered no 

later than 12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis up 
to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or 
pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by subcutaneous injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status 

(e.g. mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered subcutaneously either as a once daily injection of 150 IU/kg 

(1.5 mg/kg) or as twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 



 

204 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by subcutaneous injection administered in combination with 

antiplatelet therapy. Treatment should be maintained for a minimum of 2 days and continued until 

clinical stabilization. The usual duration of treatment is 2 to 8 days.  

 Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral 
loading dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 

75-325 mg/day long-term regardless of treatment strategy. 

 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) subcutaneous dose followed by 100 IU/kg 

(1 mg/kg) administered subcutaneously every 12 hours (maximum 10,000 IU (100 mg) for each of the 

first two subcutaneous doses). Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg 

to 325 mg once daily) should be administered concomitantly unless contraindicated. The 

recommended duration of treatment is 8 days or until hospital discharge, whichever comes first. When 

administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific), enoxaparin 

sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic 

therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last subcutaneous dose of enoxaparin sodium was given 

less than 8 hours before balloon inflation, no additional dosing is needed. If the last 

subcutaneous administration was given more than 8 hours before balloon inflation, an 

intravenous bolus of 30 IU/kg (0.3 mg/kg) enoxaparin sodium should be administered. 

 

Special populations 

 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below paragraph “Renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥75 years of age, an initial intravenous bolus must not be 

used. Initiate dosing with 75 IU/kg (0.75 mg/kg) subcutaneously every 12 hours (maximum 7,500 IU 

(75 mg) for each of the first two subcutaneous doses only, followed by 75 IU/kg (0.75 mg/kg) subcutaneous 

dosing for the remaining doses). For dosage in elderly patients with impaired kidney function, see below 

“renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

Severe renal impairment  

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 

<15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease 2,000 IU (20 mg) subcutaneously once daily 

Treatment of  DVT and PE 100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of acute STEMI (patients under 75) 

 

 

1 x 3,000 IU (30 mg) intravenous bolus plus 100 IU/kg 

(1 mg/kg) body weight subcutaneously and then 100 IU/kg 

(1 mg/kg) body weight subcutaneously every 24 hours 



 

205 

 

 

Treatment of acute STEMI (patients over 75) 

 

No intravenous initial bolus, 100 IU/kg (1 mg/kg) body 

weight subcutaneously and then 100 IU/kg (1 mg/kg) body 

weight subcutaneously every 24 hours 

 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

Moderate and mild renal impairment 

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 

30-50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring 

is advised. 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established.  

No data are available. 

 

Inhixa multidose vial contains benzyl alcohol and must not be used in newborn and premature neonates 

(see section 4.3). 

 

Method of administration  

 

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thromboembolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by subcutaneous 

injection. 

 For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately 
followed by a subcutaneous injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The use of a tuberculin syringe or equivalent is recommended when using multiple-dose vials to assure 

withdrawal of the appropriate volume of drug. 

 

Subcutaneous injection technique 

Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep subcutaneous injection.  

 

The air bubble should not be expelled from the syringe before the injection to avoid the loss of drug when 

using pre-filled syringes. When the quantity of drug to be injected requires to be adjusted based on the 

patient’s body weight, the graduated pre-filled syringes should be used to reach the required volume by 

discarding the excess before injection. In some cases it is not possible to achieve an exact dose due to the 

graduations on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. The injection 

site should not be rubbed after administration. 

 

Intravenous (bolus) injection (for acute STEMI indication only) 

For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately followed 

by a subcutaneous injection.  

For intravenous injection, either the multidose vial or pre-filled syringe can be used. 



 

206 

 

Enoxaparin sodium should be administered through an intravenous line. It should not be mixed or co-

administered with other medicinal products. To avoid the possible mixture of enoxaparin sodium with other 

drugs, the intravenous access chosen should be flushed with a sufficient amount of sodium chloride 9 mg/mL 

(0.9%) solution for infusion or glucose solution prior to and following the intravenous bolus administration 

of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely administered with sodium 

chloride 9 mg/mL (0.9%) solution for infusion or 5% glucose in water for injections. 

 

Initial 3,000 IU (30 mg) bolus 

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the intravenous line. 

 

Additional bolus for PCI when last subcutaneous administration was given more than 8 hours before balloon 

inflation 

For patients being managed with PCI, an additional intravenous bolus of 30 IU/kg (0.3 mg/kg) is to be 

administered if last subcutaneous administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either normal sodium chloride 9 mg/mL (0.9%) 

solution for infusion or 5% glucose in water for injections) as follows:  

30 mL of the solution should be withdrawn from the infusion bag with a syringe and discarded. The 

complete contents of the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe should be injected into the 

20 mL remaining in the bag. The contents of the bag should be gently mixed. Then, the required volume of 

diluted solution should be withdrawn with a syringe for administration into the intravenous line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 

Volume to be injected through intravenous line after dilution is completed at a concentration of 300 IU (3 

mg)/mL. 

 

Weight 
Required dose 

30 IU/kg (0.3 mg/kg) 

Volume to inject when diluted to 

a final concentration of 

300 IU (3 mg)/mL 

[kg] IU [mg] [mL] 

45 1,350 13.5 4.5 

50 1,500 15 5 

55 1,650 16.5 5.5 

60 1,800 18 6 

65 1,950 19.5 6.5 

70 2,100 21 7 

75 2,250 22.5 7.5 

80 2,400 24 8 

85 2,550 25.5 8.5 

90 2,700 27 9 

95 2,850 28.5 9.5 

100 3,000 30 10 

105 3,150 31.5 10.5 

110 3,300 33 11 

115 3,450 34.5 11.5 

120 3,600 36 12 

125 3,750 37.5 12.5 

130 3,900 39 13 



 

207 

 

135 4,050 40.5 13.5 

140 4,200 42 14 

145 4,350 43.5 14.5 

150 4,500 45 15 

 

Arterial line injection 

It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 

Switch between enoxaparin sodium and oral anticoagulants 

Switch between enoxaparin sodium and vitamin K antagonists (VKA)  

Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalised Ratio 

(INR)] must be intensified to monitor the effect of VKA. 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 

For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

 

At doses used for prophylaxis 

A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin sodium at 

prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with neuraxial 

anaesthesia. 

 

At doses used for treatment 

A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin sodium at 

curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg (1 mg/kg) 

twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay before catheter 

placement or removal.  

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 



 

208 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH), to benzyl alcohol or any other of the excipients listed in section 6.1; 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

Because of the content of benzyl alcohol (see section 6.1), enoxaparin sodium multiple dose vial formulation 

must not be given to newborns or premature neonates (see sections 4.4 and 4.6). 

 

4.4 Special warnings and precautions for use 
 

General 

 

Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

History of HIT (>100 days) 

 

Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-

induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such 

a case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments 

are considered (e.g. danaparoid sodium or lepirudin). 

 

Monitoring of platelet counts 

 

The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 

 

Haemorrhage 

 

As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  



 

209 

 

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 
- neuro- or ophthalmologic surgery, 
- concomitant use of medicinal products affecting haemostasis (see section 4.5). 

 

Laboratory tests 

 

At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

Spinal/Epidural anaesthesia or lumbar puncture 

 

Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 

To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach 

a sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance 

[15-30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is 

more prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

Skin necrosis / cutaneous vasculitis 

 

Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

Percutaneous coronary revascularization procedures 

 

To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 



 

210 

 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last intravenous/ subcutaneous enoxaparin sodium injection. If the 

treatment with enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 

6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or 

hematoma formation. 

 

Acute infective endocarditis 

 

Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after 

a careful individual benefit risk assessment. 

 

Mechanical prosthetic heart valves 

 

The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 

Pregnant women with mechanical prosthetic heart valves 

The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg ) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

Elderly 

 

No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

Renal impairment 

 

 In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which 
increases the risk of bleeding. In these patients, careful clinical monitoring is advised, and biological 

monitoring by anti-Xa activity measurement might be considered (see sections 4.2 and 5.2). 

 Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 
<15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 

Hepatic impairment 

 



 

211 

 

Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

Low weight 

 

An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

Obese Patients 

 

Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI >30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 

 

Hyperkalaemia 

 

Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  

Traceability 

 

LMWHs are biological medicinal products In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded. 

  

Benzyl alcohol 

 

Benzyl alcohol may cause allergic reactions. 

Intravenous administration of benzyl alcohol has been associated with serious adverse events and death in 

neonates (“Gasping Syndrome”) (see section 4.3). The minimum amount of benzyl alcohol at which toxicity 

may occur is not known. Benzyl alcohol may also cause toxic reactions in infants and children up to 3 years 

old, due to increased risk of accumulation. 

High volumes of medicinal products containing benzyl alcohol should be used with caution and only if 

necessary in patients with liver or kidney impairment, or in pregnant women, because of the risk of 

accumulation of benzyl alcohol and its toxicity (metabolic acidosis). 

 

Sodium 

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose within the recommended dose 

range, that is to say essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended 

 

Medicinal products affecting haemostasis (see section 4.4) 

It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 



 

212 

 

 

Concomitant use with caution 

 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  

- Systemic glucocorticoids. 
 

Medicinal products increasing potassium levels 

Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 

As benzyl alcohol may cross the placenta, it is recommended to use a formulation that does not contain 

benzyl alcohol. 

 

Breast-feeding  

 

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely. Inhixa can be used during breastfeeding. 

 

Fertility 

 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 



 

213 

 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) subcutaneously once daily for prophylaxis of deep vein 

thrombosis following surgery or in acutely ill medical patients with severely restricted mobility. In treatment 

of DVT with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg 

(1 mg/kg) subcutaneous dose every 12 hours or a 150 IU/kg (1.5 mg/kg) subcutaneous dose once a day. In 

the clinical studies for treatment of unstable angina and non-Q-wave myocardial infarction, doses were 

100 IU/kg (1 mg/kg) subcutaneously every 12 hours, and in the clinical study for treatment of acute STEMI 

enoxaparin sodium regimen was a 3,000 IU (30 mg) intravenous bolus followed by 100 IU/kg (1 mg/kg) 

subcutaneously every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see sections 4.4 and “Description of selected adverse reactions” below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 

(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

o Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 
o Rare: Eosinophilia* 
o Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 

complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

o Common: Allergic reaction 
o Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

o Common: Headache* 
 

Vascular disorders 

o Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees 
of neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 

o Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of 
normality) 

o Uncommon: Hepatocellular liver injury *  
o Rare: Cholestatic liver injury* 
 

Skin and subcutaneous tissue disorders 

o Common: Urticaria, pruritus, erythema 
o Uncommon: Bullous dermatitis 
o Rare: Alopecia* 
o Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena 

have been usually preceded by purpura or erythematous plaques, infiltrated and painful). 



 

214 

 

 Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 
resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

o Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 

General disorders and administration site conditions 

o Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

o Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

o Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medicinal products affecting 

haemostasis (see sections 4.4 and 4.5). 

 

System 

organ 

class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymphatic 

system 

disorders 

Very common:  

Haemorrhage
α
 

 

Rare:  

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage
α
  

Very common: 

Haemorrhage
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common:  

Haemorrhage
α
 

 

Rare:  

Retroperitoneal 

haemorrhage 

Common:  

Haemorrhage
α
 

 

Uncommon:  

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and gastro-intestinal 

haemorrhage. 

 

Thrombocytopenia and thrombocytosis 

System 

organ 

class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymphatic 

system 

disorders 

Very common:  

Thrombo-

cytosis
β
 

 

Common:  

Thrombo-

cytopenia 

Uncommon:  

Thrombo-

cytopenia 

Very common: 

Thrombo-cytosis
β
 

 

Common: 

Thrombo-

cytopenia 

Uncommon:  

Thrombo-

cytopenia 

Common:   

Thrombocytosis
β
 

Thrombo-

cytopenia 

Very rare:     

Immuno-allergic 

thrombo-

cytopenia 
β
: Platelet increased >400 G/L  



 

215 

 

 

Paediatric population 

 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Intravenous administration of benzyl alcohol has been associated with serious adverse events and death in 

neonates (“Gasping Syndrome”) (see section 4.3). 

Benzyl alcohol may also cause toxic reactions in infants and children up to 3 years old, due to increased risk 

of accumulation (see section 4.4). 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

 

Accidental overdose with enoxaparin sodium after intravenous, extracorporeal or subcutaneous 

administration may lead to haemorrhagic complications. Following oral administration of even large doses, it 

is unlikely that enoxaparin sodium will be absorbed. 

 

Management 

 

The anticoagulant effects can be largely neutralized by the slow intravenous injection of protamine. The dose 

of protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the 

anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the 

previous 8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be 

administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine 

administration, or if it has been determined that a second dose of protamine is required. After 12 hours of the 

enoxaparin sodium injection, protamine administration may not be required. However, even with high doses 

of protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 

60%) (see the prescribing information for protamine salts). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

Pharmacodynamic effects 

 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

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216 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

Extended prophylaxis of VTE following orthopaedic surgery  

In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 

179 patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin 

sodium 4,000 IU (40 mg) subcutaneously, were randomized to a post-discharge regimen of either enoxaparin 

sodium 4,000 IU (40 mg) (n=90) once a day subcutaneously or to placebo (n=89) for 3 weeks. The incidence 

of DVT during extended prophylaxis was significantly lower for enoxaparin sodium compared to placebo, no 

PE was reported. No major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) once a day 

subcutaneously 

n (%) 

Placebo  

once a day subcutaneously 

n (%) 

All treated extended prophylaxis patients 90 (100) 89 (100) 

Total VTE (%) 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)* 18 (20.2) 

 Proximal DVT (%) 5 (5.6)
#
 7 (8.8) 

*p value versus placebo =0.008 

#p value versus placebo =0.537 

 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) subcutaneously were 

randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n=131) once a day 

subcutaneously or to placebo (n=131) for 3 weeks. Similar to the first study the incidence of VTE during 

extended prophylaxis was significantly lower for enoxaparin sodium compared to placebo for both total VTE 

(enoxaparin sodium 21 [16%] versus placebo 45 [34.4%]; p=0.001) and proximal DVT (enoxaparin sodium 

8 [6.1%] versus placebo 28 [21.4%]; p=<0.001). No difference in major bleeding was found between the 

enoxaparin sodium and the placebo group. 

 

Extended prophylaxis of DVT following cancer surgery 

A double-blind, multicentre trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) subcutaneously) daily for 6 to 10 days 

and were then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. 

Bilateral venography was performed between days 25 and 31, or sooner if symptoms of venous 

thromboembolism occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis 

for four weeks after surgery for abdominal or pelvic cancer significantly reduced the incidence of 

venographically demonstrated thrombosis, as compared with enoxaparin sodium prophylaxis for one week. 

The rates of venous thromboembolism at the end of the double-blind phase were 12.0 % (n=20) in the 

placebo group and 4.8% (n=8) in the enoxaparin sodium group; p=0.02. This difference persisted at three 

months [13.8% vs. 5.5% (n=23 vs 9), p=0.01]. There were no differences in the rates of bleeding or other 

complications during the double-blind or follow-up periods. 

 

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217 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicentre, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day subcutaneously was compared to placebo in the prophylaxis of DVT in medical patients 

with severely restricted mobility during acute illness (defined as walking distance of <10 meters for 

≤3 days). This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

least one VTE risk factor (age ≥75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day subcutaneously, 

enoxaparin sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are 

provided in the table below. 

 

 Enoxaparin sodium  

2,000 IU (20 mg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg) 

once a day 

subcutaneously 

n (%) 

Placebo  

n (%) 

All treated medical patients 

during acute illness 

287 (100) 291(100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5) 40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 

VTE = Venous thromboembolic events which included DVT, PE, and death considered to be thromboembolic in origin 

* p value versus placebo = 0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicentre, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day subcutaneously, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours subcutaneously, or 

(iii) heparin intravenous bolus (5,000 IU) followed by a continuous infusion (administered to achieve an 

aPTT of 55 to 85 seconds). A total of 900 patients were randomized in the study and all patients were 

treated. All patients also received warfarin sodium (dose adjusted according to prothrombin time to achieve 

an INR of 2.0 to 3.0), commencing within 72 hours of initiation of enoxaparin sodium or standard heparin 

therapy, and continuing for 90 days. Enoxaparin sodium or standard heparin therapy was administered for a 

minimum of 5 days and until the targeted warfarin sodium INR was achieved. Both enoxaparin sodium 

regimens were equivalent to standard heparin therapy in reducing the risk of recurrent venous 

thromboembolism (DVT and/or PE). The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  
150 IU/kg (1.5 mg/kg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

100 IU/kg (1 mg/kg) 

twice a day 

subcutaneously 

n (%) 

Heparin  

aPTT Adjusted Intravenous 

Therapy 

n (%) 

All treated DVT patients 

with or without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

 DVT only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

 Proximal DVT (%) 9 (3.0) 6 (1.9) 7 (2.4) 

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&audience=consumer#footnote-40


 

218 

 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 

VTE = venous thromboembolic event (DVT and/or PE) 

* The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  
- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicentre study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either subcutaneously enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or intravenous 

unfractionated heparin adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 

2 days and a maximum of 8 days, until clinical stabilization, revascularization procedures or hospital 

discharge. The patients had to be followed up to 30 days. In comparison with heparin, enoxaparin sodium 

significantly reduced the combined incidence of angina pectoris, myocardial infarction and death, with a 

decrease of 19.8 to 16.6% (relative risk reduction of 16.2%) on day 14. This reduction in the combined 

incidence was maintained after 30 days (from 23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the 

subcutaneous injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicentre study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) intravenous bolus plus a 

100 IU/kg (1 mg/kg) subcutaneous dose followed by an subcutaneous injection of 100 IU/kg (1 mg/kg) every 

12 hours or intravenous unfractionated heparin adjusted based on aPTT for 48 hours. All patients were also 

treated with acetylsalicylic acid for a minimum of 30 days. The enoxaparin sodium dosing strategy was 

adjusted for severe renally impaired patients and for the elderly of at least 75 years of age. The subcutaneous 

injections of enoxaparin sodium were given until hospital discharge or for a maximum of eight days 

(whichever came first). 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last 

subcutaneous administration given less than 8 hours before balloon inflation, intravenous bolus of 30 IU/ kg 

(0.3 mg/kg) enoxaparin sodium, if the last subcutaneous administration given more than 8 hours before 

balloon inflation. 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p<0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p<0.001). 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p=0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage 

(a measure of net clinical benefit) was significantly lower (p<0.0001) in the enoxaparin sodium group 

(10.1%) as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of 

treatment with enoxaparin sodium. 

The incidence of major bleeding at 30 days was significantly higher (p<0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 



 

219 

 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated subcutaneous administration and after single intravenous administration. The quantitative 

determination of anti-Xa and anti-IIa pharmacokinetic activities was conducted by validated amidolytic 

methods. 

 

Absorption 

 

The absolute bioavailability of enoxaparin sodium after subcutaneous injection, based on anti-Xa activity, is 

close to 100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after subcutaneous injection and 

achieves approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single subcutaneous administration of 

2,000 IU, 4,000 IU, 100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 

 

A 3,000 IU (30 mg) intravenous bolus immediately followed by a 100 IU/kg (1 mg/kg) subcutaneously every 

12 hours provided initial maximum anti-Xa activity level of 1.16 IU/mL (n=16) and average exposure 

corresponding to 88% of steady-state levels. Steady-state is achieved on the second day of treatment. 

 

After repeated subcutaneous administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once 

daily regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio 

about 15% higher than after a single dose. After repeated subcutaneous administration of the 100 IU/kg 

(1 mg/kg) twice daily regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% 

higher than after a single dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 

0.52 IU/mL, respectively.  

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated subcutaneous administration no 

accumulation takes place. 

 

Plasma anti-IIa activity after subcutaneous administration is approximately ten-fold lower than anti-Xa 

activity. The mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following 

subcutaneous injection and reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 

100 IU/kg (1 mg/kg) twice daily and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

 



 

220 

 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 

 

Biotransformation 

 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerisation to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour intravenous infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single subcutaneous dose to about 

7 hours after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal. However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine 

clearance <30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) intravenous dose however, AUC was two-fold higher than control. 

 

Weight 

After repeated subcutaneous 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is 

marginally higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese 

control subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-

adjusted clearance in obese subjects with subcutaneous dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single-subcutaneous 4,000 IU 

(40 mg) dose, that anti-Xa exposure is 52% higher in low-weight women (<45 kg) and 27% higher in low-

weight men (<57 kg) when compared to normal weight control subjects (see section 4.4). 

 



 

221 

 

Pharmacokinetic interactions 

 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week subcutaneous toxicity studies both in rats and dogs and at  10 mg/kg/day in the 

26-week subcutaneous and intravenous toxicity studies both in rats, and monkeys. 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at subcutaneous doses of enoxaparin sodium up to 

30 mg/kg/day did not reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was 

found to have no effect on fertility or reproductive performance of male and female rats at subcutaneous 

doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Benzyl alcohol 

Water for injections 

 

6.2 Incompatibilities 
 

Subcutaneous injection 

 

Do not mix with other medicinal products. 

 

Intravenous (Bolus) injection (for acute STEMI indication only) 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in section 

6.6. 

 

6.3 Shelf life 

 

3 years 

 

After first opening 

 

Chemical and physical in-use stability has been demonstrated for 28 days at 25°C.  

From a microbiological point of view, once opened, the product may be stored for a maximum of 28 days 

below 25°C. Other in-use storage times and conditions are the responsibility of the user. 

 

After dilution with sodium chloride 9 mg/ml (0.9%) solution for infusion or 5% glucose solution for 

injection 

 

Chemical and physical in-use stability has been demonstrated for 8 hours at 25°C.  

From a microbiological point of view, unless the method of dilution precludes the risk of microbial 

contamination, the product should be used immediately. If not used immediately, in-use storage times and 

conditions are the responsibility of user. 

 



 

222 

 

6.4 Special precautions for storage 

 

Store below 25°C. Do not freeze. 

For storage conditions after first opening and dilution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

5 mL of solution in clear, colourless type I glass vial sealed with rubber injection stopper and grey 

aluminium-plastic cap in a cardboard box. 

 

Pack-sizes of 5 vials containing 5 mL. 

 

6.6 Special precautions for disposal and other handling 
 

Enoxaparin sodium may be safely administered with sodium chloride 9 mg/ml (0.9%) solution for infusion 

or 5% glucose solution for injection (see section 4.2). 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/072 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu.  

http://www.ema.europa.eu/


 

223 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of new 

safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 

4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT  
 

Inhixa 100,000 IU (1000 mg)/10 mL solution for injection in multidose vial 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One vial contains enoxaparin sodium 100,000 IU anti-Xa activity (equivalent to 1000 mg) in 10.0 mL water 

for injections. 

 

Each mL contains 10,000 IU (100 mg) enoxaparin sodium. 

 

Enoxaparin sodium is a biological substance obtained by alkaline depolymerisation of heparin benzyl ester 

derived from porcine intestinal mucosa. 

 

Excipient(s) with known effect 

 

Benzyl alcohol (150 mg in 10.0 mL) 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Solution for injection in multidose vial 

Clear, colourless to pale yellow solution 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Inhixa is indicated in adults for:  

 Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in 
particular those undergoing orthopaedic or general surgery including cancer surgery. 

 Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute 
heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility 

at increased risk of venous thromboembolism (VTE).  

 Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to 
require thrombolytic therapy or surgery. 

 Prevention of thrombus formation in extra corporeal circulation during haemodialysis. 

 Acute coronary syndrome:  
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), 

in combination with oral acetylsalicylic acid. 

- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to 
be managed medically or with subsequent percutaneous coronary intervention (PCI). 

 



 

224 

 

4.2 Posology and method of administration 

 

Posology 

 

Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients 

Individual thromboembolic risk for patients can be estimated using validated risk stratification model. 

 In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 
2,000 IU (20 mg) once daily by subcutaneous injection. Preoperative initiation (2 hours before 

surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk 

surgery.  

 In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 
7-10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the 

patient no longer has significantly reduced mobility. 

 In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU 
(40 mg) once daily given by subcutaneous injection preferably started 12 hours before surgery. If there 

is a need for earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high 

risk patient waiting for a deferred orthopaedic surgery), the last injection should be administered no 

later than 12 hours prior to surgery and resumed 12 hours after surgery. 

o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis up 
to 5 weeks is recommended.  

o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or 
pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is 

recommended. 

 

Prophylaxis of venous thromboembolism in medical patients 

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by subcutaneous injection.  

Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status 

(e.g. mobility). The benefit is not established for a treatment longer than 14 days. 

 

Treatment of DVT and PE 

Enoxaparin sodium can be administered subcutaneously either as a once daily injection of 150 IU/kg 

(1.5 mg/kg) or as twice daily injections of 100 IU/kg (1 mg/kg). 

The regimen should be selected by the physician based on an individual assessment including evaluation of 

the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) 

administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose 

regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those 

with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. 

 

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy 

should be initiated when appropriate (see “Switch between enoxaparin sodium and oral anticoagulants” at 

the end of section 4.2). 

 

Prevention of thrombus formation during haemodialysis  

The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium. 

For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double 

vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.  

 

During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the 

beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if 

fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg 

(0.5 to 1 mg/kg) may be given. 

 

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during 

haemodialysis sessions. 

 



 

225 

 

Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI 

 For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 
100 IU/kg (1 mg/kg) every 12 hours by subcutaneous injection administered in combination with 

antiplatelet therapy. Treatment should be maintained for a minimum of 2 days and continued until 

clinical stabilization. The usual duration of treatment is 2 to 8 days.  

 Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral 
loading dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 

75-325 mg/day long-term regardless of treatment strategy. 

 For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous 
bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) subcutaneous dose followed by 100 IU/kg 

(1 mg/kg) administered subcutaneously every 12 hours (maximum 10,000 IU (100 mg) for each of the 

first two subcutaneous doses). Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg 

  to 325 mg once daily) should be administered concomitantly unless contraindicated. The 
recommended duration of treatment is 8 days or until hospital discharge, whichever comes first. When 

administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific), enoxaparin 

sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic 

therapy. 

o For dosage in patients ≥ 75 years of age, see paragraph “Elderly”. 
o For patients managed with PCI, if the last subcutaneous dose of enoxaparin sodium was given 

less than 8 hours before balloon inflation, no additional dosing is needed. If the last 

subcutaneous administration was given more than 8 hours before balloon inflation, an 

intravenous bolus of 30 IU/kg (0.3 mg/kg) enoxaparin sodium should be administered. 

 

Special populations 

 

Elderly 

For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney 

function is impaired (see below paragraph “Renal impairment” and section 4.4). 

For treatment of acute STEMI in elderly patients ≥75 years of age, an initial intravenous bolus must not be 

used. Initiate dosing with 75 IU/kg (0.75 mg/kg) subcutaneously every 12 hours (maximum 7,500 IU 

(75 mg) for each of the first two subcutaneous doses only, followed by 75 IU/kg (0.75 mg/kg) subcutaneous 

dosing for the remaining doses). For dosage in elderly patients with impaired kidney function, see below 

“renal impairment” and section 4.4. 

 

Hepatic impairment 

Limited data are available in patients with hepatic impairment (see sections 5.1 and 5.2) and caution should 

be used in these patients (see section 4.4). 

 

Renal impairment (see sections 4.4 and 5.2) 

Severe renal impairment  

Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 

<15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

 

Dosage table for patients with severe renal impairment (creatinine clearance [15-30] mL/min): 

 

Indication Dosing regimen 

Prophylaxis of venous thromboembolic disease 2,000 IU (20 mg) subcutaneously once daily 

Treatment of  DVT and PE 100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of unstable angina and NSTEMI  100 IU/kg (1 mg/kg) body weight subcutaneously once daily 

Treatment of acute STEMI (patients under 75) 

 

 

1 x 3,000 IU (30 mg) intravenous bolus plus 100 IU/kg 

(1 mg/kg) body weight subcutaneously and then 100 IU/kg 

(1 mg/kg) body weight subcutaneously every 24 hours 



 

226 

 

 

Treatment of acute STEMI (patients over 75) 

 

No intravenous initial bolus, 100 IU/kg (1 mg/kg) body 

weight subcutaneously and then 100 IU/kg (1 mg/kg) body 

weight subcutaneously every 24 hours 

 

The recommended dosage adjustments do not apply to the haemodialysis indication. 

 

Moderate and mild renal impairment 

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 

30-50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring 

is advised. 

 

Paediatric population 

The safety and efficacy of enoxaparin sodium in paediatric population have not been established.  

No data are available. 

 

Inhixa multidose vial contains benzyl alcohol and must not be used in newborn and premature neonates 

(see section 4.3). 

 

Method of administration  

 

Inhixa should not be administered by the intramuscular route. 

 

For the prophylaxis of venous thromboembolic disease following surgery, treatment of DVT and PE, 

treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by subcutaneous 

injection. 

 For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately 
followed by a subcutaneous injection. 

 For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis, it is 
administered through the arterial line of a dialysis circuit.  

 

The use of a tuberculin syringe or equivalent is recommended when using multiple-dose vials to assure 

withdrawal of the appropriate volume of drug. 

 

Subcutaneous injection technique 

Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by 

deep subcutaneous injection.  

 

The air bubble should not be expelled from the syringe before the injection to avoid the loss of drug when 

using pre-filled syringes. When the quantity of drug to be injected requires to be adjusted based on the 

patient’s body weight, the graduated pre-filled syringes should be used to reach the required volume by 

discarding the excess before injection. In some cases it is not possible to achieve an exact dose due to the 

graduations on the syringe, and in such case the volume shall be rounded up to the nearest graduation.  

 

The administration should be alternated between the left and right anterolateral or posterolateral abdominal 

wall. 

 

The whole length of the needle should be introduced vertically into a skin fold gently held between the 

thumb and index finger. The skin fold should not be released until the injection is complete. The injection 

site should not be rubbed after administration. 

 

Intravenous (bolus) injection (for acute STEMI indication only) 

For acute STEMI, treatment is to be initiated with a single intravenous bolus injection immediately followed 

by a subcutaneous injection.  

For intravenous injection, either the multidose vial or pre-filled syringe can be used. 



 

227 

 

Enoxaparin sodium should be administered through an intravenous line. It should not be mixed or co-

administered with other medicinal products. To avoid the possible mixture of enoxaparin sodium with other 

drugs, the intravenous access chosen should be flushed with a sufficient amount of sodium chloride 9 mg/mL 

(0.9%) solution for infusion or glucose solution prior to and following the intravenous bolus administration 

of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely administered with sodium 

chloride 9 mg/mL (0.9%) solution for infusion or 5% glucose in water for injections. 

 

Initial 3,000 IU (30 mg) bolus 

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the 

excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be 

directly injected into the intravenous line. 

 

Additional bolus for PCI when last subcutaneous administration was given more than 8 hours before balloon 

inflation 

For patients being managed with PCI, an additional intravenous bolus of 30 IU/kg (0.3 mg/kg) is to be 

administered if last subcutaneous administration was given more than 8 hours before balloon inflation. 

 

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 

300 IU/mL (3 mg/mL). 

To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe, 

it is recommended to use a 50 mL infusion bag (i.e. using either normal sodium chloride 9 mg/mL (0.9%) 

solution for infusion or 5% glucose in water for injections) as follows:  

30 mL of the solution should be withdrawn from the infusion bag with a syringe and discarded. The 

complete contents of the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe should be injected into the 

20 mL remaining in the bag. The contents of the bag should be gently mixed. Then, the required volume of 

diluted solution should be withdrawn with a syringe for administration into the intravenous line. 

 

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume 

of diluted solution (mL) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare 

the dilution immediately before use. 

 

Volume to be injected through intravenous line after dilution is completed at a concentration of 300 IU (3 

mg)/mL. 

 

Weight 
Required dose 

30 IU/kg (0.3 mg/kg) 

Volume to inject when diluted to 

a final concentration of 

300 IU (3 mg)/mL 

[kg] IU [mg] [mL] 

45 1,350 13.5 4.5 

50 1,500 15 5 

55 1,650 16.5 5.5 

60 1,800 18 6 

65 1,950 19.5 6.5 

70 2,100 21 7 

75 2,250 22.5 7.5 

80 2,400 24 8 

85 2,550 25.5 8.5 

90 2,700 27 9 

95 2,850 28.5 9.5 

100 3,000 30 10 

105 3,150 31.5 10.5 

110 3,300 33 11 

115 3,450 34.5 11.5 

120 3,600 36 12 

125 3,750 37.5 12.5 

130 3,900 39 13 



 

228 

 

135 4,050 40.5 13.5 

140 4,200 42 14 

145 4,350 43.5 14.5 

150 4,500 45 15 

 

Arterial line injection 

It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the 

extra corporeal circulation during haemodialysis. 

 

Switch between enoxaparin sodium and oral anticoagulants 

Switch between enoxaparin sodium and vitamin K antagonists (VKA)  

Clinical monitoring and laboratory tests [prothrombin time expressed as the International Normalised Ratio 

(INR)] must be intensified to monitor the effect of VKA. 

As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be 

continued at a constant dose for as long as necessary in order to maintain the INR within the desired 

therapeutic range for the indication in two successive tests. 

For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin 

sodium should be given when the INR has dropped below the therapeutic range. 

 

Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) 

For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 

2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per 

DOAC label. 

For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the 

next DOAC dose would be taken. 

 

Administration in spinal/epidural anaesthesia or lumbar puncture  

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of 

neuraxial haematomas (see section 4.4).  

 

At doses used for prophylaxis 

A puncture-free interval of at least 12 hours shall be kept between the last injection of enoxaparin sodium at 

prophylactic doses and the needle or catheter placement. 

For continuous techniques, a similar delay of at least 12 hours should be observed before removing the 

catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 24 hours. 

The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with neuraxial 

anaesthesia. 

 

At doses used for treatment 

A puncture-free interval of at least 24 hours shall be kept between the last injection of enoxaparin sodium at 

curative doses and the needle or catheter placement (see also section 4.3).  

For continuous techniques, a similar delay of 24 hours should be observed before removing the catheter.  

For patients with creatinine clearance [15-30] mL/min, consider doubling the timing of puncture/catheter 

placement or removal to at least 48 hours. 

Patients receiving the twice daily doses (i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg (1 mg/kg) 

twice-daily) should omit the second enoxaparin sodium dose to allow a sufficient delay before catheter 

placement or removal.  

Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial 

hematoma will be avoided.  

Likewise, consider not using enoxaparin sodium until at least 4 hours after the spinal/epidural puncture or 

after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both 

the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. 

 



 

229 

 

4.3 Contraindications 
 

Enoxaparin sodium is contraindicated in patients with: 

 Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular 
weight heparins (LMWH), to benzyl alcohol or any other of the excipients listed in section 6.1; 

 History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in 
the presence of circulating antibodies (see also section 4.4 ); 

 Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent 
haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, 

recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous 

malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities; 

 Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for 
treatment in the previous 24 hours (see section 4.4). 

Because of the content of benzyl alcohol (see section 6.1), enoxaparin sodium multiple dose vial formulation 

must not be given to newborns or premature neonates (see sections 4.4 and 4.6). 

 

4.4 Special warnings and precautions for use 
 

General 

 

Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal 

products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, 

units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated 

biological activities (e.g. anti-thrombin activity, and platelet interactions). Special attention and compliance 

with the instructions for use specific to each proprietary medicinal product are therefore required.  

 

History of HIT (>100 days) 

 

Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in 

the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist 

several years. 

Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-

induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such 

a case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments 

are considered (e.g. danaparoid sodium or lepirudin). 

 

Monitoring of platelet counts 

 

The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually 

appears between the 5
th
 and the 21

st
 day following the beginning of enoxaparin sodium treatment.  

The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with 

cancer. 

Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with 

enoxaparin sodium and then regularly thereafter during the treatment. 

If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous 

thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on 

treatment), platelet count should be measured. Patients must be aware that these symptoms may occur and if 

so, that they should inform their primary care physician. 

In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial 

value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another 

non-heparin anticoagulant alternative treatment. 

 

Haemorrhage 

 

As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the 

haemorrhage should be investigated and appropriate treatment instituted.  



 

230 

 

Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with 

increased potential for bleeding, such as: 

- impaired haemostasis,  
- history of peptic ulcer, 
- recent ischemic stroke,  
- severe arterial hypertension,  
- recent diabetic retinopathy, 
- neuro- or ophthalmologic surgery, 
- concomitant use of medicinal products affecting haemostasis (see section 4.5). 

 

Laboratory tests 

 

At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding 

time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of 

fibrinogen to platelets. 

At higher doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) 

may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium 

antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium 

activity. 

 

Spinal/Epidural anaesthesia or lumbar puncture 

 

Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of 

enoxaparin sodium at therapeutic doses (see also section 4.3). 

There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and 

spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis. 

These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The 

risk of these events is higher with the use of post-operative indwelling epidural catheters, with the 

concomitant use of additional drugs affecting haemostasis such as Non-Steroidal Anti-Inflammatory Drugs 

(NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal 

surgery or spinal deformity. 

 

To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and 

epidural or spinal anaesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of 

enoxaparin sodium (see section 5.2). Placement or removal of an epidural catheter or lumbar puncture is best 

performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach 

a sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance 

[15-30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is 

more prolonged (see section 4.2). 

 

Should the physician decide to administer anticoagulation in the context of epidural or spinal 

anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and 

symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or 

weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they 

experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 

initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though 

such treatment may not prevent or reverse neurological sequelae.   

 

Skin necrosis / cutaneous vasculitis 

 

Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment 

discontinuation. 

 

Percutaneous coronary revascularization procedures 

 

To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable 

angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin 



 

231 

 

sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure 

device is used, the sheath can be removed immediately. If a manual compression method is used, sheath 

should be removed 6 hours after the last intravenous/ subcutaneous enoxaparin sodium injection. If the 

treatment with enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 

6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or 

hematoma formation. 

 

Acute infective endocarditis 

 

Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of 

cerebral haemorrhage.  If such use is considered absolutely necessary, the decision must be made only after 

a careful individual benefit risk assessment. 

 

Mechanical prosthetic heart valves 

 

The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with 

mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in 

patients with mechanical prosthetic heart valves who have received enoxaparin sodium for 

thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit 

the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal 

and foetal death.  

 

Pregnant women with mechanical prosthetic heart valves 

The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart 

valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic 

heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg ) twice daily) to reduce the risk of 

thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal 

and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women 

with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. 

Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. 

 

Elderly 

 

No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly 

patients (especially patients eighty years of age and older) may be at an increased risk for bleeding 

complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction 

might be considered in patients older than 75 years treated for STEMI (see sections 4.2 and 5.2).  

 

Renal impairment 

 

 In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which 
increases the risk of bleeding. In these patients, careful clinical monitoring is advised, and biological 

monitoring by anti-Xa activity measurement might be considered (see sections 4.2 and 5.2). 

 Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance 
<15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extra 

corporeal circulation during haemodialysis. 

In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin 

sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic 

dosage ranges (see section 4.2).  

No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and 

mild (creatinine clearance 50-80 mL/min) renal impairment. 

 

Hepatic impairment 

 



 

232 

 

Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased 

potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with 

liver cirrhosis and not recommended (see section 5.2). 

 

Low weight 

 

An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been 

observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of 

bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2). 

 

Obese Patients 

 

Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in 

obese patients (BMI >30 kg/m2) has not been fully determined and there is no consensus for dose 

adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. 

 

Hyperkalaemia 

 

Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia (see section 4.8), 

particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic 

acidosis, taking medicinal products known to increase potassium (see section 4.5). Plasma potassium should 

be monitored regularly especially in patients at risk. 

  

Traceability 

 

LMWHs are biological medicinal products. In order to improve the traceability of biological medicinal 

products, the name and the batch number of the administered product should be clearly recorded . 

 

Benzyl alcohol 

 

Benzyl alcohol may cause allergic reactions. 

Intravenous administration of benzyl alcohol has been associated with serious adverse events and death in 

neonates (“Gasping Syndrome”) (see section 4.3). The minimum amount of benzyl alcohol at which toxicity 

may occur is not known. Benzyl alcohol may also cause toxic reactions in infants and children up to 3 years 

old, due to increased risk of accumulation. 

High volumes of medicinal products containing benzyl alcohol should be used with caution and only if 

necessary in patients with liver or kidney impairment, or in pregnant women, because of the risk of 

accumulation of benzyl alcohol and its toxicity (metabolic acidosis). 

 

Sodium 

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose within the recommended dose 

range, that is to say essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Concomitant use not recommended 

 

Medicinal products affecting haemostasis (see section 4.4) 

It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin 

sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used 

with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products 

such as: 

- Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including 
ketorolac, 

- Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and 
anticoagulants (see section 4.2). 



 

233 

 

 

Concomitant use with caution 

 

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium: 

Other medicinal products affecting haemostasis such as: 

- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose 
(cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in 

acute coronary syndrome due to the risk of bleeding, 

- Dextran 40,  

- Systemic glucocorticoids. 
 

Medicinal products increasing potassium levels 

Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin 

sodium under careful clinical and laboratory monitoring (see sections 4.4 and 4.8).  

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third 

trimester of pregnancy. There is no information available concerning the first trimester.  

Animal studies have not shown any evidence of foetotoxicity or teratogenicity (see section 5.3). Animal data 

have shown that enoxaparin passage through the placenta is minimal. 

Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. 

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or 

excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there 

is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the 

risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart 

valves (see section 4.4).  

 

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before 

(see section 4.4). 

 

As benzyl alcohol may cross the placenta, it is recommended to use a formulation that does not contain 

benzyl alcohol. 

 

Breast-feeding  

 

It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the 

passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is 

unlikely. Inhixa can be used during breastfeeding. 

 

Fertility 

 

There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in 

clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or 



 

234 

 

abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein 

thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or 

without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for 

treatment of acute STEMI.  

 

Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The 

enoxaparin sodium dose was 4,000 IU (40 mg) subcutaneously once daily for prophylaxis of deep vein 

thrombosis following surgery or in acutely ill medical patients with severely restricted mobility. In treatment 

of DVT with or without PE, patients receiving enoxaparin sodium were treated with either a 100 IU/kg 

(1 mg/kg) subcutaneous dose every 12 hours or a 150 IU/kg (1.5 mg/kg) subcutaneous dose once a day. In 

the clinical studies for treatment of unstable angina and non-Q-wave myocardial infarction, doses were 

100 IU/kg (1 mg/kg) subcutaneously every 12 hours, and in the clinical study for treatment of acute STEMI 

enoxaparin sodium regimen was a 3,000 IU (30 mg) intravenous bolus followed by 100 IU/kg (1 mg/kg) 

subcutaneously every 12 hours.  

 

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported 

reactions (see sections 4.4 and “Description of selected adverse reactions” below). 

 

Tabulated summary list of adverse reactions 

 

Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates 

reactions from post-marketing experience) are detailed below.  

Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 

(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be 

estimated from available data). Within each system organ class, adverse reactions are presented in order of 

decreasing seriousness. 

 

Blood and the lymphatic system disorders 

o Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis 
o Rare: Eosinophilia* 
o Rare: Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was 

complicated by organ infarction or limb ischaemia (see section 4.4). 

 

Immune system disorders 

o Common: Allergic reaction 
o Rare: Anaphylactic/Anaphylactoid reactions including shock* 
 

Nervous system disorders 

o Common: Headache* 
 

Vascular disorders 

o Rare: Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees 
of neurologic injuries including long-term or permanent paralysis (see section 4.4). 

 

Hepato-biliary disorders 

o Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of 
normality) 

o Uncommon: Hepatocellular liver injury *  
o Rare: Cholestatic liver injury* 
 

Skin and subcutaneous tissue disorders 

o Common: Urticaria, pruritus, erythema 
o Uncommon: Bullous dermatitis 
o Rare: Alopecia* 
o Rare: Cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena 

have been usually preceded by purpura or erythematous plaques, infiltrated and painful). 



 

235 

 

 Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They 
resolve after a few days and should not cause treatment discontinuation. 

 

Musculoskeletal, connective tissue and bone disorders 

o Rare: Osteoporosis* following long term therapy (greater than 3 months) 
 

General disorders and administration site conditions 

o Common: Injection site haematoma, injection site pain, other injection site reaction (such as oedema, 
haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)  

o Uncommon: Local irritation, skin necrosis at injection site 
 

Investigations 

o Rare: Hyperkalaemia* (see sections 4.4 and 4.5). 
 

Description of selected adverse reactions 

 

Haemorrhages 

These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients). Some of 

these cases have been fatal. In surgical patients, haemorrhage complications were considered major: (1) if the 

haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or 

transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always 

considered major.  

As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as: 

organic lesions liable to bleed, invasive procedures or the concomitant use of medicinal products affecting 

haemostasis (see sections 4.4 and 4.5). 

 

System 

organ 

class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymphatic 

system 

disorders 

Very common:  

Haemorrhage
α
 

 

Rare:  

Retroperitoneal 

haemorrhage 

Common: 

Haemorrhage
α
  

Very common: 

Haemorrhage
α
 

 

Uncommon: 

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 

Common:  

Haemorrhage
α
 

 

Rare:  

Retroperitoneal 

haemorrhage 

Common:  

Haemorrhage
α
 

 

Uncommon:  

Intracranial 

haemorrhage, 

Retroperitoneal 

haemorrhage 
α
: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and gastro-intestinal 

haemorrhage. 

 

Thrombocytopenia and thrombocytosis 

System 

organ 

class 

Prophylaxis in 

surgical patients 

Prophylaxis in 

medical patients 

Treatment in 

patients with 

DVT with or 

without PE 

Treatment in 

patients with 

unstable angina 

and non-Q-wave 

MI 

Treatment in 

patients with 

acute STEMI  

Blood 

and 

lymphatic 

system 

disorders 

Very common:  

Thrombo-

cytosis
β
 

 

Common:  

Thrombo-

cytopenia 

Uncommon:  

Thrombo-

cytopenia 

Very common: 

Thrombo-cytosis
β
 

 

Common: 

Thrombo-

cytopenia 

Uncommon:  

Thrombo-

cytopenia 

Common:   

Thrombocytosis
β
 

Thrombo-

cytopenia 

Very rare:     

Immuno-allergic 

thrombo-

cytopenia 
β
: Platelet increased >400 G/L  



 

236 

 

 

Paediatric population 

 

The safety and efficacy of enoxaparin sodium in children have not been established (see section 4.2). 

 

Intravenous administration of benzyl alcohol has been associated with serious adverse events and death in 

neonates (“Gasping Syndrome”) (see section 4.3). 

Benzyl alcohol may also cause toxic reactions in infants and children up to 3 years old, due to increased risk 

of accumulation (see section 4.4). 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V.  

 

4.9 Overdose 

 

Signs and symptoms 

 

Accidental overdose with enoxaparin sodium after intravenous, extracorporeal or subcutaneous 

administration may lead to haemorrhagic complications. Following oral administration of even large doses, it 

is unlikely that enoxaparin sodium will be absorbed. 

 

Management 

 

The anticoagulant effects can be largely neutralized by the slow intravenous injection of protamine. The dose 

of protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the 

anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the 

previous 8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be 

administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine 

administration, or if it has been determined that a second dose of protamine is required. After 12 hours of the 

enoxaparin sodium injection, protamine administration may not be required. However, even with high doses 

of protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 

60%) (see the prescribing information for protamine salts). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antithrombotic agents, heparin group. ATC code: B01A B05 

 

Inhixa is a biosimilar medicinal product. Detailed information is available on the website of the European 

Medicines Agency http://www.ema.europa.eu.  

 

Pharmacodynamic effects 

 

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the 

antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is 

the sodium salt.  

 

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) 

and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant 

activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/


 

237 

 

Beyond its anti-Xa/IIa activity, further antithrombotic and anti-inflammatory properties of enoxaparin have 

been identified in healthy subjects and patients as well as in non-clinical models. 

These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of 

endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand 

factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute 

to the overall antithrombotic effect of enoxaparin sodium. 

When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT. When used 

as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity. 

 

Clinical efficacy and safety 

 

Prevention of venous thromboembolic disease associated with surgery 

Extended prophylaxis of VTE following orthopaedic surgery  

In a double blind study of extended prophylaxis for patients undergoing hip replacement surgery, 

179 patients with no venous thromboembolic disease initially treated, while hospitalized, with enoxaparin 

sodium 4,000 IU (40 mg) subcutaneously, were randomized to a post-discharge regimen of either enoxaparin 

sodium 4,000 IU (40 mg) (n=90) once a day subcutaneously or to placebo (n=89) for 3 weeks. The incidence 

of DVT during extended prophylaxis was significantly lower for enoxaparin sodium compared to placebo, no 

PE was reported. No major bleeding occurred. 

The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  

4,000 IU (40 mg) once a day 

subcutaneously 

n (%) 

Placebo  

once a day subcutaneously 

n (%) 

All treated extended prophylaxis patients 90 (100) 89 (100) 

Total VTE (%) 6 (6.6) 18 (20.2) 

 Total DVT (%) 6 (6.6)* 18 (20.2) 

 Proximal DVT (%) 5 (5.6)
#
 7 (8.8) 

*p value versus placebo =0.008 

#p value versus placebo =0.537 

 

In a second double-blind study, 262 patients without VTE disease and undergoing hip replacement surgery 

initially treated, while hospitalized, with enoxaparin sodium 4,000 IU (40 mg) subcutaneously were 

randomized to a post-discharge regimen of either enoxaparin sodium 4,000 IU (40 mg) (n=131) once a day 

subcutaneously or to placebo (n=131) for 3 weeks. Similar to the first study the incidence of VTE during 

extended prophylaxis was significantly lower for enoxaparin sodium compared to placebo for both total VTE 

(enoxaparin sodium 21 [16%] versus placebo 45 [34.4%]; p=0.001) and proximal DVT (enoxaparin sodium 

8 [6.1%] versus placebo 28 [21.4%]; p=<0.001). No difference in major bleeding was found between the 

enoxaparin sodium and the placebo group. 

 

Extended prophylaxis of DVT following cancer surgery 

A double-blind, multicentre trial, compared a four-week and a one-week regimen of enoxaparin sodium 

prophylaxis in terms of safety and efficacy in 332 patients undergoing elective surgery for abdominal or 

pelvic cancer. Patients received enoxaparin sodium (4,000 IU (40 mg) subcutaneously) daily for 6 to 10 days 

and were then randomly assigned to receive either enoxaparin sodium or placebo for another 21 days. 

Bilateral venography was performed between days 25 and 31, or sooner if symptoms of venous 

thromboembolism occurred. The patients were followed for three months. Enoxaparin sodium prophylaxis 

for four weeks after surgery for abdominal or pelvic cancer significantly reduced the incidence of 

venographically demonstrated thrombosis, as compared with enoxaparin sodium prophylaxis for one week. 

The rates of venous thromboembolism at the end of the double-blind phase were 12.0 % (n=20) in the 

placebo group and 4.8% (n=8) in the enoxaparin sodium group; p=0.02. This difference persisted at three 

months [13.8% vs. 5.5% (n=23 vs 9), p=0.01]. There were no differences in the rates of bleeding or other 

complications during the double-blind or follow-up periods. 

 

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&audience=consumer#footnote-32


 

238 

 

Prophylaxis of venous thromboembolic disease in medical patients with an acute illness expected to induce 

limitation of mobility 

In a double blind multicentre, parallel group study, enoxaparin sodium 2,000 IU (20 mg) or 4,000 IU 

(40 mg) once a day subcutaneously was compared to placebo in the prophylaxis of DVT in medical patients 

with severely restricted mobility during acute illness (defined as walking distance of <10 meters for 

≤3 days). This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or 

complicated chronic respiratory insufficiency, and acute infection or acute rheumatic; if associated with at 

least one VTE risk factor (age ≥75 years, cancer, previous VTE, obesity, varicose veins, hormone therapy, 

and chronic heart or respiratory failure). 

A total of 1,102 patients were enrolled in the study, and 1,073 patients were treated. Treatment continued for 

6 to 14 days (median duration 7 days). When given at a dose of 4,000 IU (40 mg) once a day subcutaneously, 

enoxaparin sodium significantly reduced the incidence of VTE as compared to placebo. The efficacy data are 

provided in the table below. 

 

 Enoxaparin sodium  

2,000 IU (20 mg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

4,000 IU (40 mg) 

once a day 

subcutaneously 

n (%) 

Placebo  

n (%) 

All treated medical patients 

during acute illness 

287 (100) 291(100) 288 (100) 

Total VTE (%) 43 (15.0) 16 (5.5)* 43 (14.9) 

 Total DVT (%) 43 (15.0) 16 (5.5) 40 (13.9) 

 Proximal DVT (%) 13 (4.5) 5 (1.7) 14 (4.9) 

VTE = Venous thromboembolic events which included DVT, PE, and death considered to be thromboembolic in origin 

* p value versus placebo = 0.0002 

 

At approximately 3 months following enrolment, the incidence of VTE remained significantly lower in the 

enoxaparin sodium 4,000 IU (40 mg) treatment group versus the placebo treatment group. 

The occurrence of total and major bleeding were respectively 8.6% and 1.1% in the placebo group, 11.7% 

and 0.3% in the enoxaparin sodium 2,000 IU (20 mg) group and 12.6% and 1.7% in the enoxaparin sodium 

4,000 IU (40 mg) group. 

 

Treatment of deep vein thrombosis with or without pulmonary embolism  

In a multicentre, parallel group study, 900 patients with acute lower extremity DVT with or without PE were 

randomized to an inpatient (hospital) treatment of either (i) enoxaparin sodium 150 IU/kg (1.5 mg/kg) once 

a day subcutaneously, (ii) enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours subcutaneously, or 

(iii) heparin intravenous bolus (5,000 IU) followed by a continuous infusion (administered to achieve an 

aPTT of 55 to 85 seconds). A total of 900 patients were randomized in the study and all patients were 

treated. All patients also received warfarin sodium (dose adjusted according to prothrombin time to achieve 

an INR of 2.0 to 3.0), commencing within 72 hours of initiation of enoxaparin sodium or standard heparin 

therapy, and continuing for 90 days. Enoxaparin sodium or standard heparin therapy was administered for a 

minimum of 5 days and until the targeted warfarin sodium INR was achieved. Both enoxaparin sodium 

regimens were equivalent to standard heparin therapy in reducing the risk of recurrent venous 

thromboembolism (DVT and/or PE). The efficacy data are provided in the table below. 

 

 Enoxaparin sodium  
150 IU/kg (1.5 mg/kg) 

once a day 

subcutaneously 

n (%) 

Enoxaparin sodium  

100 IU/kg (1 mg/kg) 

twice a day 

subcutaneously 

n (%) 

Heparin  

aPTT Adjusted Intravenous 

Therapy 

n (%) 

All treated DVT patients 

with or without PE 

298 (100) 312 (100) 290 (100) 

Total VTE (%) 13 (4.4)* 9 (2.9)* 12 (4.1) 

 DVT only (%) 11 (3.7) 7 (2.2) 8 (2.8) 

 Proximal DVT (%) 9 (3.0) 6 (1.9) 7 (2.4) 

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&audience=consumer#footnote-40


 

239 

 

 PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 

VTE = venous thromboembolic event (DVT and/or PE) 

* The 95% Confidence Intervals for the treatment differences for total VTE were:  

- enoxaparin sodium once a day versus heparin (-3.0 to 3.5)  
- enoxaparin sodium every 12 hours versus heparin (-4.2 to 1.7). 

 

Major bleeding were respectively 1.7% in the enoxaparin sodium 150 IU/kg (1.5 mg/kg) once a day group, 

1.3% in the enoxaparin sodium 100 IU/kg (1 mg/kg) twice a day group and 2.1% in the heparin group. 

 

Treatment of unstable angina and non ST elevation myocardial infarction 

In a large multicentre study, 3,171 patients enrolled at the acute phase of unstable angina or non-Q-wave 

myocardial infarction were randomized to receive in association with acetylsalicylic acid (100 to 325 mg 

once daily), either subcutaneously enoxaparin sodium 100 IU/kg (1 mg/kg) every 12 hours or intravenous 

unfractionated heparin adjusted based on aPTT. Patients had to be treated in hospital for a minimum of 

2 days and a maximum of 8 days, until clinical stabilization, revascularization procedures or hospital 

discharge. The patients had to be followed up to 30 days. In comparison with heparin, enoxaparin sodium 

significantly reduced the combined incidence of angina pectoris, myocardial infarction and death, with a 

decrease of 19.8 to 16.6% (relative risk reduction of 16.2%) on day 14. This reduction in the combined 

incidence was maintained after 30 days (from 23.3 to 19.8%; relative risk reduction of 15%). 

There were no significant differences in major haemorrhages, although a haemorrhage at the site of the 

subcutaneous injection was more frequent. 

 

Treatment of acute ST-segment elevation myocardial infarction 

In a large multicentre study, 20,479 patients with STEMI eligible to receive fibrinolytic therapy were 

randomized to receive either enoxaparin sodium in a single 3,000 IU (30 mg) intravenous bolus plus a 

100 IU/kg (1 mg/kg) subcutaneous dose followed by an subcutaneous injection of 100 IU/kg (1 mg/kg) every 

12 hours or intravenous unfractionated heparin adjusted based on aPTT for 48 hours. All patients were also 

treated with acetylsalicylic acid for a minimum of 30 days. The enoxaparin sodium dosing strategy was 

adjusted for severe renally impaired patients and for the elderly of at least 75 years of age. The subcutaneous 

injections of enoxaparin sodium were given until hospital discharge or for a maximum of eight days 

(whichever came first). 

4,716 patients underwent percutaneous coronary intervention receiving antithrombotic support with blinded 

study drug. Therefore, for patients on enoxaparin sodium, the PCI was to be performed on enoxaparin 

sodium (no switch) using the regimen established in previous studies i.e. no additional dosing, if last 

subcutaneous administration given less than 8 hours before balloon inflation, intravenous bolus of 30 IU/ kg 

(0.3 mg/kg) enoxaparin sodium, if the last subcutaneous administration given more than 8 hours before 

balloon inflation. 

Enoxaparin sodium compared to unfractionated heparin significantly decreased the incidence of  the primary 

end point, a composite of death from any cause or myocardial re-infarction in the first 30 days after 

randomization [9.9 percent in the enoxaparin sodium group, as compared with 12.0 percent in the 

unfractionated heparin group] with a 17 percent relative risk reduction (p<0.001). 

The treatment benefits of enoxaparin sodium, evident for a number of efficacy outcomes, emerged at 

48 hours, at which time there was a 35 percent reduction in the relative risk of myocardial re-infarction, as 

compared with treatment with unfractionated heparin (p<0.001). 

The beneficial effect of enoxaparin sodium on the primary end point was consistent across key subgroups 

including age, gender, infarct location, history of diabetes, history of prior myocardial infarction, type of 

fibrinolytic administered, and time to treatment with study drug. 

There was a significant treatment benefit of enoxaparin sodium, as compared with unfractionated heparin, in 

patients who underwent percutaneous coronary intervention within 30 days after randomization (23 percent 

reduction in relative risk) or who were treated medically (15 percent reduction in relative risk, p=0.27 for 

interaction). 

The rate of the 30 day composite endpoint of death, myocardial re-infarction or intracranial haemorrhage 

(a measure of net clinical benefit) was significantly lower (p<0.0001) in the enoxaparin sodium group 

(10.1%) as compared to the heparin group (12.2%), representing a 17% relative risk reduction in favour of 

treatment with enoxaparin sodium. 

The incidence of major bleeding at 30 days was significantly higher (p<0.0001) in the enoxaparin sodium 

group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in 



 

240 

 

the enoxaparin sodium group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial 

haemorrhage was similar in both groups (0.8% with enoxaparin sodium versus 0.7% with heparin). 

The beneficial effect of enoxaparin sodium on the primary end point observed during the first 30 days was 

maintained over a 12 month follow-up period. 

 

Hepatic impairment 

Based on literature data the use of enoxaparin sodium 4,000 IU (40 mg) in cirrhotic patients (Child-Pugh 

class B-C) appears to be safe and effective in preventing portal vein thrombosis. It should be noted that the 

literature studies may have limitations. Caution should be used in patients with hepatic impairment as these 

patients have an increased potential for bleeding (see section 4.4) and no formal dose finding studies have 

been performed in cirrhotic patients (Child Pugh class A, B nor C). 

 

5.2 Pharmacokinetic properties 
 

General characteristics 

 

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time 

course of plasma anti-Xa activity and also by anti-IIa activity, at the recommended dosage ranges after single 

and repeated subcutaneous administration and after single intravenous administration. The quantitative 

determination of anti-Xa and anti-IIa pharmacokinetic activities was conducted by validated amidolytic 

methods. 

 

Absorption 

 

The absolute bioavailability of enoxaparin sodium after subcutaneous injection, based on anti-Xa activity, is 

close to 100%. 

 

Different doses and formulations and dosing regimens can be used. 

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after subcutaneous injection and 

achieves approximately 0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single subcutaneous administration of 

2,000 IU, 4,000 IU, 100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg) doses, respectively. 

 

A 3,000 IU (30 mg) intravenous bolus immediately followed by a 100 IU/kg (1 mg/kg) subcutaneously every 

12 hours provided initial maximum anti-Xa activity level of 1.16 IU/mL (n=16) and average exposure 

corresponding to 88% of steady-state levels. Steady-state is achieved on the second day of treatment. 

 

After repeated subcutaneous administration of 4,000 IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once 

daily regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio 

about 15% higher than after a single dose. After repeated subcutaneous administration of the 100 IU/kg 

(1 mg/kg) twice daily regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% 

higher than after a single dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 

0.52 IU/mL, respectively.  

 

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic 

parameters in healthy volunteers. 

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges. 

Intra-patient and inter-patient variability is low. Following repeated subcutaneous administration no 

accumulation takes place. 

 

Plasma anti-IIa activity after subcutaneous administration is approximately ten-fold lower than anti-Xa 

activity. The mean maximum anti-IIa activity level is observed approximately 3 to 4 hours following 

subcutaneous injection and reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 

100 IU/kg (1 mg/kg) twice daily and 150 IU/kg (1.5 mg/kg) once daily, respectively. 

 

Distribution 

 



 

241 

 

The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood 

volume. 

 

Biotransformation 

 

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerisation to lower 

molecular weight species with much reduced biological potency. 

 

Elimination 

 

Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU 

/kg (1.5 mg/kg) 6-hour intravenous infusion. 

Elimination appears monophasic with a half-life of about 5 hours after a single subcutaneous dose to about 

7 hours after repeated dosing. 

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion 

of active and non-active fragments 40% of the dose. 

 

Special populations 

 

Elderly 

Based on the results of a population pharmacokinetic analysis, the enoxaparin sodium kinetic profile is not 

different in elderly subjects compared to younger subjects when renal function is normal. However, since 

renal function is known to decline with age, elderly patients may show reduced elimination of enoxaparin 

sodium (see sections 4.2 and 4.4). 

 

Hepatic impairment 

In a study conducted in patients with advanced cirrhosis treated with enoxaparin sodium 4,000 IU (40 mg) 

once daily, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic 

impairment (assessed by Child-Pugh categories). This decrease was mainly attributed to a decrease in ATIII 

level secondary to a reduced synthesis of ATIII in patients with hepatic impairment. 

 

Renal impairment 

A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been 

observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. 

Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 

50-80 mL/min) and moderate (creatinine clearance 30-50 mL/min) renal impairment after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses. In patients with severe renal impairment (creatinine 

clearance <30 mL/min), the AUC at steady state is significantly increased on average by 65% after repeated 

subcutaneous 4,000 IU (40 mg) once daily doses (see sections 4.2 and 4.4). 

 

Haemodialysis 

Enoxaparin sodium pharmacokinetics appeared similar than control population, after a single 25 IU, 50 IU or 

100 IU/kg (0.25, 0.50 or 1.0 mg/kg) intravenous dose however, AUC was two-fold higher than control. 

 

Weight 

After repeated subcutaneous 150 IU/kg (1.5 mg/kg) once daily dosing, mean AUC of anti-Xa activity is 

marginally higher at steady state in obese healthy volunteers (BMI 30-48 kg/m
2
) compared to non-obese 

control subjects, while maximum plasma anti-Xa activity level is not increased. There is a lower weight-

adjusted clearance in obese subjects with subcutaneous dosing. 

 

When non-weight adjusted dosing was administered, it was found after a single-subcutaneous 4,000 IU 

(40 mg) dose, that anti-Xa exposure is 52% higher in low-weight women (<45 kg) and 27% higher in low-

weight men (<57 kg) when compared to normal weight control subjects (see section 4.4). 

 



 

242 

 

Pharmacokinetic interactions 

 

No pharmacokinetic interactions were observed between enoxaparin sodium and thrombolytics when 

administered concomitantly. 

 

5.3 Preclinical safety data 
 

Besides the anticoagulant effects of enoxaparin sodium, there was no evidence of adverse effects at 

15 mg/kg/day in the 13-week subcutaneous toxicity studies both in rats and dogs and at  10 mg/kg/day in the 

26-week subcutaneous and intravenous toxicity studies both in rats, and monkeys. 

 

Enoxaparin sodium has shown no mutagenic activity based on in vitro tests, including the Ames test, mouse 

lymphoma cell forward mutation test, and no clastogenic activity based on an in vitro human lymphocyte 

chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test. 

 

Studies conducted in pregnant rats and rabbits at subcutaneous doses of enoxaparin sodium up to 

30 mg/kg/day did not reveal any evidence of teratogenic effects or foetotoxicity. Enoxaparin sodium was 

found to have no effect on fertility or reproductive performance of male and female rats at subcutaneous 

doses up to 20 mg/kg/day.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Benzyl alcohol 

Water for injections 

 

6.2 Incompatibilities 
 

Subcutaneous injection 

 

Do not mix with other medicinal products. 

 

Intravenous (Bolus) injection (for acute STEMI indication only) 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in section 

6.6. 

 

6.3 Shelf life 

 

3 years 

 

After first opening 

 

Chemical and physical in-use stability has been demonstrated for 28 days at 25°C.  

From a microbiological point of view, once opened, the product may be stored for a maximum of 28 days 

below 25°C. Other in-use storage times and conditions are the responsibility of the user. 

 

After dilution with sodium chloride 9 mg/ml (0.9%) solution for infusion or 5% glucose solution for 

injection 

 

Chemical and physical in-use stability has been demonstrated for 8 hours at 25°C.  

From a microbiological point of view, unless the method of dilution precludes the risk of microbial 

contamination, the product should be used immediately. If not used immediately, in-use storage times and 

conditions are the responsibility of user. 

 



 

243 

 

6.4 Special precautions for storage 

 

Store below 25°C. Do not freeze. 

For storage conditions after first opening and dilution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

10 mL of solution in clear, colourless type I glass vial sealed with rubber injection stopper and white 

aluminium-plastic cap in a cardboard box. 

 

Pack-sizes of 1 or 5 vials containing 10 mL. 

Not all pack sizes may be marketed 

 

6.6 Special precautions for disposal and other handling 
 

Enoxaparin sodium may be safely administered with sodium chloride 9 mg/ml (0.9%) solution for infusion 

or 5% glucose solution for injection (see section 4.2). 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/081 

EU/1/16/1132/082 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 15/09/2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

  

http://www.ema.europa.eu/


 

244 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 

MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 

 

 

 



 

245 

 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 

MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) of the biological active substance(s)  

 

Shenzhen Techdow Pharmaceutical Co., Ltd. 

No. 19, Gaoxinzhongyi Road, Hi-tech Industrial Park, 

Nanshan District,  

Shenzhen City,  

Guangdong Province,  

518057, People’s Republic of China 

 

Shenzhen Hepalink Pharmaceutical Group Co., Ltd.  

No. 1 Rongtian South, Kengzi Sub-district  

Pingshan New District, Shenzhen  

518122, People’s Republic of China 

 

Name and address of the manufacturer(s) responsible for batch release 

 

Health-Med spółka z ograniczoną odpowiedzialnością sp.k. 

Chełmska 30/34 

00-725 Warsaw 

Poland 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription.  

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  

 

 Periodic safety update reports (PSURs) 
 

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 

reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 

subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 

 

 Risk management plan (RMP) 
 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and 

interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation and 

any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of an 

important (pharmacovigilance or risk minimisation) milestone being reached.   



 

246 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



 

247 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



 

248 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON (Packs of 1, 2, 6, 10, 20, 50 or 90) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inhixa 2,000 IU (20 mg)/0.2 mL solution for injection enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One pre-filled syringe (0.2 mL) contains 2,000 IU (20 mg) enoxaparin sodium  

 

 

3. LIST OF EXCIPIENTS 

 

Water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection  

1 pre-filled syringe 

2 pre-filled syringes 

6 pre-filled syringes 

10 pre-filled syringes 

50 pre-filled syringes 

2 pre-filled syringes with needle guard 

6 pre-filled syringes with needle guard 

10 pre-filled syringes with needle guard 

20 pre-filled syringes with needle guard 

50 pre-filled syringes with needle guard 

90 pre-filled syringes with needle guard 

2 pre-filled syringes with UltraSafe Passive needle guard 

6 pre-filled syringes with UltraSafe Passive needle guard 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single use only.  

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 



 

249 

 

8. EXPIRY DATE 

 

EXP 

The diluted solution must be used within 8 hours. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25 °C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/021 

EU/1/16/1132/001 

EU/1/16/1132/033 

EU/1/16/1132/002 

EU/1/16/1132/064 

EU/1/16/1132/011 

EU/1/16/1132/034 

EU/1/16/1132/012 

EU/1/16/1132/023 

EU/1/16/1132/065 

EU/1/16/1132/051 

EU/1/16/1132/053 

EU/1/16/1132/054 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 



 

250 

 

 

Inhixa 2,000 IU (20 mg)/0.2 mL 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:   

SN:   

NN:   

  



 

251 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 2,000 IU (20 mg)/0.2 mL injection 

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

  



 

252 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF (Packs of 2, 5, 6, 10, 20, 30, 50 or 90) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inhixa 4,000 IU (40 mg) /0.4 mL solution for injection 

enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One pre-filled syringe (0.4 mL) contains 4,000 IU (40 mg) enoxaparin sodium 

 

 

3. LIST OF EXCIPIENTS 

 

Water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection  

2 pre-filled syringes 

5 pre-filled syringes6 pre-filled syringes 

10 pre-filled syringes 

30 pre-filled syringes 

50 pre-filled syringes 

2 pre-filled syringes with needle guard 

5 pre-filled syringes with needle guard 

6 pre-filled syringes with needle guard 

10 pre-filled syringes with needle guard 

20 pre-filled syringes with needle guard 

30 pre-filled syringes with needle guard 

50 pre-filled syringes with needle guard 

90 pre-filled syringes with needle guard 

2 pre-filled syringes with UltraSafe Passive needle guard 

6 pre-filled syringes with UltraSafe Passive needle guard 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single use only.  

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 



 

253 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

The diluted solution must be used within 8 hours. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25 °C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/003 

EU/1/16/1132/066 

EU/1/16/1132/035 

EU/1/16/1132/004 

EU/1/16/1132/043 

EU/1/16/1132/068 

EU/1/16/1132/013 

EU/1/16/1132/067 

EU/1/16/1132/036 

EU/1/16/1132/014 

EU/1/16/1132/024 

EU/1/16/1132/044 

EU/1/16/1132/025 

EU/1/16/1132/052 

EU/1/16/1132/055 

EU/1/16/1132/056 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 



 

254 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Inhixa 4,000 IU (40 mg)/0.4 mL 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:   

SN:   

NN:    



 

255 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 4,000 IU (40 mg) /0.4 mL injection  

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 

  



 

256 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF (Packs of 2, 6, 10, 12, 20, 24 or 30) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inhixa 6,000 IU (60 mg)/0.6 mL solution for injection  

enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One pre-filled syringe (0.6 mL) contains 6,000 IU (60 mg) enoxaparin sodium 

 

 

3. LIST OF EXCIPIENTS 

 

Water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection  

2 pre-filled syringes 

6 pre-filled syringes 

10 pre-filled syringes 

30 pre-filled syringes 

50 pre-filled syringes 

2 pre-filled syringes with needle guard 

6 pre-filled syringes with needle guard 

10 pre-filled syringes with needle guard 

12 pre-filled syringes with needle guard 

20 pre-filled syringes with needle guard 

24 pre-filled syringes with needle guard 

30 pre-filled syringes with needle guard 

2 pre-filled syringes with UltraSafe Passive needle guard 

10 pre-filled syringes with UltraSafe Passive needle guard 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single use only.  

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 



 

257 

 

 

 

8. EXPIRY DATE 

 

EXP 

The diluted solution must be used within 8 hours. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25 °C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/005 

EU/1/16/1132/037 

EU/1/16/1132/006 

EU/1/16/1132/045 

EU/1/16/1132/083 

EU/1/16/1132/015 

EU/1/16/1132/038 

EU/1/16/1132/016 

EU/1/16/1132/026 

EU/1/16/1132/027 

EU/1/16/1132/028 

EU/1/16/1132/046 

EU/1/16/1132/057 

EU/1/16/1132/058 

 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

15. INSTRUCTIONS ON USE 

 



 

258 

 

 

16. INFORMATION IN BRAILLE 

 

Inhixa 6,000 IU (60 mg)/0.6 mL 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:   

SN:   

NN:    



 

259 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 6,000 IU (60 mg)/0.6 mL injection  

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

  



 

260 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF (Packs of 2, 6, 10, 12, 24 or 30) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inhixa 8,000 IU (80 mg)/0.8 mL solution for injection 

enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One pre-filled syringe (0.8 mL) contains 8,000 IU (80 mg) enoxaparin sodium 

 

 

3. LIST OF EXCIPIENTS 

 

Water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection  

2 pre-filled syringes 

6 pre-filled syringes  

10 pre-filled syringes 

30 pre-filled syringes 

50 pre-filled syringes 

2 pre-filled syringes with needle guard 

6 pre-filled syringes with needle guard 

10 pre-filled syringes with needle guard 

12 pre-filled syringes with needle guard 

24 pre-filled syringes with needle guard 

30 pre-filled syringes with needle guard 

2 pre-filled syringes with UltraSafe Passive needle guard 

10 pre-filled syringes with UltraSafe Passive needle guard 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single use only.  

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 



 

261 

 

8. EXPIRY DATE 

 

EXP 

The diluted solution must be used within 8 hours. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25 °C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/007 

EU/1/16/1132/039 

EU/1/16/1132/008 

EU/1/16/1132/047 

EU/1/16/1132/084 

EU/1/16/1132/017 

EU/1/16/1132/040 

EU/1/16/1132/018 

EU/1/16/1132/029 

EU/1/16/1132/030 

EU/1/16/1132/048 

EU/1/16/1132/059 

EU/1/16/1132/060 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

15. INSTRUCTIONS ON USE 

 

 



 

262 

 

16. INFORMATION IN BRAILLE 

 

Inhixa 8,000 IU (80 mg)/0.8 mL 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:   

SN:   

NN:    



 

263 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 8,000 IU (80 mg)/0.8 mL injection  

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 

  



 

264 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF (Packs of 2, 6, 10, 12, 24, 30, 50 or 90) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inhixa 10,000 IU (100 mg)/1 mL solution for injection 

enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One pre-filled syringe (1 mL) contains 10,000 IU (100 mg) enoxaparin sodium  

 

 

3. LIST OF EXCIPIENTS 

 

Water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection  

2 pre-filled syringes 

6 pre-filled syringes 

10 pre-filled syringes 

30 pre-filled syringes 

50 pre-filled syringes 

90 pre-filled syringes 

2 pre-filled syringes with needle guard 

6 pre-filled syringes with needle guard 

10 pre-filled syringes with needle guard 

12 pre-filled syringes with needle guard 

24 pre-filled syringes with needle guard 

30 pre-filled syringes with needle guard 

2 pre-filled syringes with UltraSafe Passive needle guard 

10 pre-filled syringes with UltraSafe Passive needle guard 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single use only.  

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 



 

265 

 

 

 

8. EXPIRY DATE 

 

EXP 

The diluted solution must be used within 8 hours. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25 °C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/009 

EU/1/16/1132/041 

EU/1/16/1132/010 

EU/1/16/1132/049 

EU/1/16/1132/063 

EU/1/16/1132/022 

EU/1/16/1132/019 

EU/1/16/1132/042 

EU/1/16/1132/020 

EU/1/16/1132/031  

EU/1/16/1132/032 

EU/1/16/1132/050 

EU/1/16/1132/061 

EU/1/16/1132/062 

 

 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

15. INSTRUCTIONS ON USE 



 

266 

 

 

 

16. INFORMATION IN BRAILLE 

 

Inhixa 10,000 IU (100 mg)/1 mL 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:   

SN:   

NN:    



 

267 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 10,000 IU (100 mg) /1 mL injection  

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 

 

 

 

 

  



 

268 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON (Packs of 2, 10 or 30) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inhixa 12,000 IU (120 mg)/0.8 mL solution for injection  

enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One pre-filled syringe (0.8 mL) contains 12,000 IU (120 mg) enoxaparin sodium.  

 

 

3. LIST OF EXCIPIENTS 

 

Water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection  

2 pre-filled syringes  

10 pre-filled syringes 

30 pre-filled syringes 

10 pre-filled syringes with needle guard 

30 pre-filled syringes with needle guard 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single use only.  

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

The diluted solution must be used within 8 hours. 

 

 



 

269 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25 °C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/069 

EU/1/16/1132/076 

EU/1/16/1132/075 

EU/1/16/1132/077 

EU/1/16/1132/073 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Inhixa 12,000 IU (120 mg)/0.8 mL 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



 

270 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 12,000 IU (120 mg)/0.8 mL injection 

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

  



 

271 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON (Packs of 2, 10 or 30) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inhixa 15,000 IU (150 mg)/1 mL solution for injection 

enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One pre-filled syringe (1 mL) contains 15,000 IU (150 mg) enoxaparin sodium 

 

 

3. LIST OF EXCIPIENTS 

 

Water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection  

2 pre-filled syringes 

10 pre-filled syringes 

30 pre-filled syringes 

10 pre-filled syringes with needle guard 

30 pre-filled syringes with needle guard 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single use only.  

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

The diluted solution must be used within 8 hours. 

 

 



 

272 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25 °C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/074 

EU/1/16/1132/078 

EU/1/16/1132/080 

EU/1/16/1132/079 

EU/1/16/1132/070 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Inhixa 15,000 IU (150 mg)/ mL 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:   

SN:   

NN:    



 

273 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 15,000 IU (150 mg)/1 mL injection  

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 

 



 

274 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER BOX MULTIDOSE VIAL 

  

 

1. NAME OF THE MEDICINAL PRODUCT 

  

Inhixa 30,000 IU (300 mg)/3 mL solution for injection in multidose vial 

enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each mL contains 10,000 IU (100 mg) enoxaparin sodium. 

One vial (3 mL) contains 30,000 IU (300 mg) enoxaparin sodium. 

 

 

3. LIST OF EXCIPIENTS 

 

Benzyl alcohol (see leaflet for further information) 

Water for injections 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in multidose vial 

1 vial 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

The contents of the multidose vial should be used within 28 days of opening. 

 

 



 

275 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25°C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/071 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Inhixa 30,000 IU (300 mg)/3 mL 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:   

SN:   

NN:    



 

276 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

MULTIPLE DOSE VIALS 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 30,000 IU (300 mg)/3 mL solution for injection in multidose vial 

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 

  



 

277 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER BOX MULTIDOSE VIAL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inhixa 50,000 IU (500 mg)/5 mL solution for injection in multidose vial 

enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each mL contains 10,000 IU (100 mg) enoxaparin sodium. 

One vial (5 mL) contains 50,000 IU (500 mg) enoxaparin sodium. 

 

 

3. LIST OF EXCIPIENTS 

 

Benzyl alcohol (see leaflet for further information) 

Water for injections 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in multidose vial 

5 vials 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

The contents of the multidose vial should be used within 28 days of opening. 

 

 



 

278 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25°C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/072 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Inhixa 50,000 IU (500 mg)/5 mL 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:   

SN:   

NN:    



 

279 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

MULTIPLE DOSE VIALS 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 50,000 IU (500 mg)/5 mL solution for injection in multidose vial 

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



 

280 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER BOX MULTIDOSE VIAL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inhixa 100,000 IU (1000 mg)/10 mL solution for injection in multidose vial 

enoxaparin sodium 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each mL contains 10,000 IU (100 mg) enoxaparin sodium. 

One vial (10 mL) contains 100,000 IU (1000 mg) enoxaparin sodium. 

 

 

3. LIST OF EXCIPIENTS 

 

Benzyl alcohol (see leaflet for further information) 

Water for injections 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection in multidose vial 

1 vial 

5 vials 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use.  

Subcutaneous, intravenous use. 

Extracorporeal use (in the dialysis circuit). 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

The contents of the multidose vial should be used within 28 days of opening. 

 

 



 

281 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25°C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1132/081 

EU/1/16/1132/082 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Inhixa 100,000 IU (1000 mg)/10 mL 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:   

SN:   

NN:    



 

282 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

MULTIPLE DOSE VIALS 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Inhixa 100,000 IU (1000 mg)/10 mL solution for injection in multidose vial 

enoxaparin sodium 

SC, IV and extracorporeal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

  



 

283 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 

  



 

284 

 

Package leaflet: Information for the user 

 

Inhixa 2,000 IU (20 mg)/0.2 mL solution for injection  

Inhixa 4,000 IU (40 mg)/0.4 mL solution for injection 

Inhixa 6,000 IU (60 mg)/0.6 mL solution for injection 

Inhixa 8,000 IU (80 mg)/0.8 mL solution for injection 

Inhixa 10,000 IU (100 mg)/1 mL solution for injection 

enoxaparin sodium 

 

This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how to 

report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains important 

information for you. 

- Keep this leaflet. You may need to read it again.  

- If you have any further questions, ask your doctor, pharmacist or nurse. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 

their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Inhixa is and what it is used for 

2. What you need to know before you use Inhixa 

3. How to use Inhixa 

4. Possible side effects 

5. How to store Inhixa  

6. Contents of the pack and other information 

 

 

1. What Inhixa is and what it is used for 

 

Inhixa contains the active substance called enoxaparin sodium that is a low molecular weight heparin 

(LMWH). 

 

Inhixa works in two ways. 

1)  Stopping existing blood clots from getting any bigger. This helps your body to break them down and 

stop them causing you harm. 

2)  Stopping blood clots forming in your blood. 

 

Inhixa can be used to: 

 Treat blood clots that are in your blood 

 Stop blood clots from forming in your blood in the following situations: 
o Before and after an operation  
o When you have an acute illness and face period of limited mobility 
o When you have unstable angina (a condition when not enough blood gets to your heart) 
o After a heart attack 

 Stop blood clots forming in the tubes of your dialysis machine (used for people with severe kidney 
problems). 

  

 

2. What you need to know before you use Inhixa 

 

Do not use Inhixa 



 

285 

 

 If you are allergic to enoxaparin sodium or any of the other ingredients of this medicine (listed in 
section 6). Signs of an allergic reaction include: rash, swallowing or breathing problems, 

swelling of your lips, face, throat or tongue. 

 If you are allergic to heparin or other low molecular weight heparins such as nadroparin, 
tinzaparin or dalteparin. 

 If you have had a reaction to heparin that caused a severe drop in the number of your clotting 
cells (platelets) - this reaction is called heparin-induced thrombocytopenia - within the last 100 

days or if you have antibodies against enoxaparin in your blood. 

 If you are bleeding heavily or have a condition with a high risk of bleeding (such as stomach 
ulcer, recent surgery of the brain or eyes), including recent bleeding stroke. 

 If you are using Inhixa to treat blood clots in your body and going to receive spinal or epidural 
anaesthesia or lumbar puncture within 24 hours. 

 

Warnings and precautions 

Inhixa should not be used interchangeably with other medicines belonging to the group of low molecular 

weight heparins. This is because they are not exactly the same and do not have the same activity and 

instructions for use. 

 

Talk to your doctor or pharmacist before using Inhixa if: 

 you have ever had a reaction to heparin that caused a severe drop in the number of your platelets 

 you are going to receive spinal or epidural anesthesia or lumbar puncture (see Operations and 
Anaesthetics): a delay should be respected between Inhixa use and this procedure. 

 you have had a heart valve fitted 

 you have endocarditis (an infection of the inner lining of the heart) 

 you have history of gastric ulcer 

 you have had a recent stroke  

 you have high blood pressure 

 you have diabetes or  problems with blood vessels in the eye caused by diabetes (called diabetic 
retinopathy)  

 you have had an operation recently on your eyes or brain 

 you are elderly (over 65 years old) and especially if you are over 75 years old 

 you have kidney problems 

 you have liver problems 

 you are underweight or overweight 

 you have high level of potassium in your blood (this may be checked with a blood test) 

 you are currently using medicines which affect bleeding (see section below – Other medicines). 
 

You may have a blood test before you start using this medicine and at intervals while you are using it; this is 

to check the level of the clotting cells (platelets) and potassium in your blood. 

 

Other medicines and Inhixa 

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 

medicines. 

 Warfarin – used for thinning the blood 

 Aspirin (also known as acetylsalicylic acid or ASA), clopidogrel or other medicines used to stop blood 
clots from forming (see also in section 3, “Changing of anticoagulant medicine”) 

 Dextran injection – used as a blood replacer 

 Ibuprofen, diclofenac, ketorolac or other medicines known as non-steroidal anti-inflammatory agents 
which are used to treat pain and swelling in arthritis and other conditions 

 Prednisolone, dexamethasone or other medicines used to treat asthma, rheumatoid arthritis and other 
conditions 

 Medicines which increase potassium level in your blood such as potassium salts, water pills, some 
medicines for heart problems. 

 

Operations and anesthetics 



 

286 

 

If you are going to have a spinal puncture or an operation where an epidural or spinal anaesthetic is used, tell 

your doctor that you are using Inhixa. See “Do not use Inhixa”. Also, tell your doctor if you have any 

problem with your spine or if you ever had spinal surgery. 

 

 

Pregnancy and breast-feeding 

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist 

for advice before taking this medicine. 

If you are pregnant and have a mechanical heart valve, you may be at an increased risk of developing blood 

clots. Your doctor should discuss this with you. 

 

If you are breast-feeding or plan to breast-feed, you should ask your doctor for advice before taking this 

medicine. 

 

Driving and using machines 

Inhixa does not affect the ability to drive and operate machinery. 

 

It is advised that the trade name and batch number of the product you are using are recorded by your 

healthcare professional. 

 

Inhixa contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 

 

3. How to use Inhixa 

 

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 

pharmacist if you are not sure. 

 

Having this medicine 

 Your doctor or nurse will normally give you Inhixa. This is because it needs to be given as an injection. 

 When you go home, you may need to continue to use Inhixa and give it yourself (see instructions below 
on how to do this). 

 Inhixa is usually given by injection underneath the skin (subcutaneous). 

 Inhixa can be given by injection into your vein (intravenous) after certain types of heart attack or 
operation. 

 Inhixa can be added to the tube leaving the body (arterial line) at the start of the dialysis session. 
Do not inject Inhixa into a muscle. 

 

How much will be given to you 

 Your doctor will decide how much Inhixa to give you. The amount will depend on the reason it is being 
used. 

 If you have problems with your kidneys you may be given a smaller amount of Inhixa. 
 

1. Treating blood clots that are in your blood 

 The usual dose is 150 IU (1.5 mg) for every kilogram of your weight each day or 100 IU (1 mg) for 
every kilogram of your weight twice a day. 

 Your doctor will decide how long you should receive Inhixa. 
 

2. Stopping blood clots forming in your blood in the following situations: 

 Operation or periods of limited mobility due to an illness 

 The dose will depend on how likely you are to develop a clot. You will be given 2,000 IU (20 mg) 
or 4,000 IU (40 mg) of Inhixa each day.  

 If you are going to have an operation your first injection will be usually given 2 hours or 12 hours 
before your operation.  



 

287 

 

 If you have restricted mobility due to illness, you will normally be given 4,000 IU (40 mg) of 
Inhixa each day. 

 Your doctor will decide how long you should receive Inhixa. 
 

 After you have had a heart attack 
Inhixa can be used for two different types of heart attack called STEMI (ST segment elevation myocardial 

infarction) or Non STEMI (NSTEMI). The amount of Inhixa given to you will depend on your age and the 

kind of heart attack you have had. 

 

NSTEMI type of heart attack:  

 The usual dose is 100 IU (1 mg) for every kilogram of weight every 12 hours.  

 Your doctor will normally ask you to take aspirin (acetylsalicylic acid) as well. 

 Your doctor will decide how long you should receive Inhixa. 
 

STEMI type of heart attack if you are under 75 years old: 

 An initial dose of 3,000 IU (30 mg) of Inhixa  will be given as injection into your vein. 

 At the same time you will also be given Inhixa as an injection underneath your skin (subcutaneous 
injection). The usual dose is 100 IU (1 mg) for every kilogram of your weight, every 12 hours.  

 Your doctor will normally ask you to take aspirin (acetylsalicylic acid) as well. 

 Your doctor will decide how long you should receive Inhixa. 
 

STEMI type of heart attack if you are 75 years old or older: 

 The usual dose is 75 IU (0.75 mg) for every kilogram of your weight, every 12 hours. 

 The maximum amount of Inhixa given for the first two injections is 7,500 IU (75 mg). 

 Your doctor will decide how long you should receive Inhixa. 
 

For patients have an operation called percutaneous coronary intervention (PCI): 

Depending on when you were last given Inhixa, your doctor may decide to give an additional dose of 

Inhixa before a PCI operation. This is by injection into your vein. 

 

3. Stopping blood clots from forming in the tubes of your dialysis machine 

 The usual dose is 100 IU (1 mg) for every kilogram of your weight. 

 Inhixa is added to the tube leaving the body (arterial line) at the start of the dialysis session. This 
amount is usually enough for a 4-hour session. However, your doctor may give you a further dose of 

50 IU to 100 IU (0.5 to 1 mg) for every kilogram of your weight, if necessary. 

 

How to give yourself an injection of Inhixa 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 



 

288 

 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin. 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold. 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection. 

 

8)  Remove the needle by pulling it straight out. 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 



 

289 

 

9)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has a needle guard attached to it in order to protect you from needle stick injury. 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin. 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold. 

 



 

290 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection. 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Push hard the plunger. The needle guard, which is in the form of a plastic cylinder, will be activated 

automatically and it will completely cover the needle. 

 
10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has UltraSafe Passive needle guard attached to it in order to protect you from needle 

stick injury.  

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 



 

291 

 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
 

Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin. 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold. 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection. 

 



 

292 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 
 

To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Let go of the plunger and allow the syringe to move up until the entire needle is guarded and locks 

into place. 

 
 

10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

Changing of anticoagulant treatment 

- Changing from Inhixa to blood thinners called vitamin-K antagonists (e.g. warfarin) 
Your doctor will request you perform blood tests called INR and tell you when to stop Inhixa 

accordingly. 

 

- Changing from blood thinners called vitamin-K antagonists (e.g. warfarin) to Inhixa   
Stop taking the vitamin-K antagonist. Your doctor will request you perform blood tests called INR and 

tell you when to start Inhixa accordingly. 

 

- Changing from Inhixa to treatment with direct oral anticoagulant Stop taking Inhixa. Start taking the 
direct oral anticoagulant 0-2 hours before the time you would have had the next injection, then continue 

as normal. 

 

- Changing from treatment with direct oral anticoagulant to Inhixa 
Stop taking direct oral anticoagulant. Do not start treatment with Inhixa until 12 hours after the final dose 

of direct oral anticoagulant. 

 

Use in children and adolescents 

The safety and efficacy of Inhixa has not been evaluated in children or adolescents.  

 

If you use more Inhixa than you should 

If you think that you have used too much or too little Inhixa, tell your doctor, nurse or pharmacist 

immediately, even if you have no signs of a problem. If a child accidentally injects or swallows Inhixa, take 

them to a hospital causualty department straight away. 

 



 

293 

 

If you forget to use Inhixa 
If you forget to give yourself a dose, have it as soon as you remember. Do not give yourself a double dose on 

the same day to make up for a forgotten dose. Keeping a diary will help to make sure you do not miss a dose. 

 

If you stop using Inhixa  

If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse. 

It is important for you to keep having Inhixa injections until your doctor decides to stop them. If you stop, 

you could get a blood clot which can be very dangerous. 

 

 

4. Possible side effects 

 

Like other similar medicines (medicines to reduce blood clotting), Inhixa may cause bleeding which may 

potentially be life-threatening. In some cases the bleeding may not be obvious. 

 

If you experience any bleeding event that does not stop by itself or if you experience signs of excessive 

bleeding (exceptional weakness, tiredness, paleness, dizziness, headache or unexplained swelling), consult 

your doctor immediately. 

Your doctor may decide to keep you under closer observation or change your medicine. 

 

Stop using Inhixa and talk to a doctor or nurse at once if you get any signs of a severe allergic reaction (such 

as difficulty breathing, swelling of the lips, mouth, throat or eyes). 

 

You should tell your doctor straight away  

 If you have any sign of blockage of a blood vessel by a blood clot such as: 
- cramping pain, redness, warmth, or swelling in one of your legs – these are symptoms of deep vein 

thrombosis 

- breathlessness, chest pain, fainting or coughing up blood – these are symptoms of a pulmonary 
embolism  

 If you have a painful rash of dark red spots under the skin which do not go away when you put pressure 
on them.  

Your doctor may request you perform a blood test to check your platelet count. 

 

Overall list of possible side effects: 

Very common ( may affect more than 1 in 10 people) 

 Bleeding. 

 Increases in liver enzymes. 
 

Common (may affect up to 1 in 10 people) 

 You bruise more easily than usual. This could be because of a blood problem with low platelet counts. 

 Pink patches on your skin. These are more likely to appear in the area you have been injected with 
Inhixa. 

 Skin rash (hives, urticaria). 

 Itchy red skin. 

 Bruising or pain at the injection site. 

 Decreased red blood cell count. 

 High platelet counts in the blood. 

 Headache. 
 

Uncommon (may affect up to 1 in 100 people) 

 Sudden severe headache. This could be a sign of bleeding in the brain.  

 A feeling of tenderness and swelling in your stomach. You may have bleeding in your stomach.  

 Large red irregularly shaped skin lesions with or without blisters. 

 Skin irritation (local irritation). 

http://www.nhs.uk/Conditions/Deep-vein-thrombosis/Pages/Symptoms.aspx
http://www.nhs.uk/Conditions/Deep-vein-thrombosis/Pages/Symptoms.aspx
http://www.nhs.uk/conditions/shortness-of-breath/Pages/Introduction.aspx
http://www.nhs.uk/conditions/chest-pain/Pages/Introduction.aspx
http://www.nhs.uk/conditions/Fainting/Pages/Introduction.aspx
http://www.nhs.uk/conditions/coughing-up-blood/Pages/Introduction.aspx
http://www.nhs.uk/Conditions/pulmonary-embolism/Pages/Symptoms.aspx
http://www.nhs.uk/Conditions/pulmonary-embolism/Pages/Symptoms.aspx


 

294 

 

 You notice yellowing of your skin or eyes and your urine becomes darker in colour. This could be a 
liver problem. 

 

Rare (may affect up to 1 in 1,000 people) 

 Severe allergic reaction.  The signs may include: a rash, swallowing or breathing problems, swelling of 
your lips, face, throat or tongue. 

 Increased potassium in your blood. This is more likely to happen in people with kidney problems or 
diabetes. Your doctor will be able to check this by carrying out a blood test. 

 An increase in the number of eosinophils in your blood. Your doctor will be able to check this by 
carrying out a blood test. 

 Hair loss.  

 Osteoporosis (a condition where your bones are more likely to break) after long term use. 

 Tingling, numbness and muscular weakness (particularly in the lower part of your body) when you 
have had a spinal puncture or a spinal anaesthetic.  

 Lost of control over your bladder or bowel (so you cannot control when you go to the toilet). 

 Hard mass or lump at the injection site.  
 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed 

in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix 

V. By reporting side effects you can help provide more information on the safety of this medicine. 

 

 

5. How to store Inhixa 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the label and carton. The expiry date refers 

to the last day of that month. 

 

Store below 25 °C. Do not freeze. 

After dilution the solution should be used within 8 hours.  

 

Do not use this medicine if you notice any visible change in the appearance of the solution. 

 

The Inhixa pre-filled syringes are for single dose use only. Discard any unused medicine. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 

away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Inhixa contains 

- The active substance is enoxaparin sodium. 

Each mL contains 100 mg enoxaparin sodium. 

Each pre-filled syringe of 0.2 mL contains 2,000 IU (20 mg) of enoxaparin sodium.  

Each pre-filled syringe of 0.4 mL contains 4,000 IU (40 mg) of enoxaparin sodium. 

Each pre-filled syringe of 0.6 mL contains 6,000 IU (60 mg) of enoxaparin sodium. 

Each pre-filled syringe of 0.8 mL contains 8,000 IU (80 mg) of enoxaparin sodium. 

Each pre-filled syringe of 1 mL contains 10,000 IU (100 mg) of enoxaparin sodium. 

-  The other ingredient is water for injections. 

 

What Inhixa looks like and contents of the pack 

Inhixa 2,000 IU (20 mg)/0.2 mL is 0.2 mL of solution in: 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

295 

 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 
chlorobutyl rubber stopper and a blue polypropylene plunger rod. The syringe can be additionally 

equipped with needle guard; or 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 

chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe Passive 

needle guard. 

 

 

Supplied in packs of:  

- 1, 2, 6, 10 and 50 pre-filled syringe(s) 
- 2, 6, 10, 20, 50 and 90 pre-filled syringes with needle guard 

- 2 and 6 pre-filled syringes with UltraSafe Passive needle guard  
 

Inhixa 4,000 IU (40 mg)/0.4 mL is 0.4 mL of solution in: 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 
chlorobutyl rubber stopper and a yellow polypropylene plunger rod. The syringe can be additionally 

equipped with needle guard; or 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 

chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe Passive 

needle guard. 

 

Supplied in packs of:  

- 2, 5, 6, 10, 30 and 50 pre-filled syringes 
- 2, 5, 6, 10, 20, 30, 50 and 90 pre-filled syringes with needle guard 

- 2 and 6 pre-filled syringes with UltraSafe Passive needle guard  
 

Inhixa 6,000 IU (60 mg)/0.6 mL is 0.6 mL of solution in: 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 
closed by chlorobutyl rubber stopper and an orange polypropylene plunger rod. The syringe can be 

additionally equipped with needle guard; or 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 

closed by chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe 

Passive needle guard. 

 

Supplied in packs of:  

- 2, 6, 10, 30 and 50 pre-filled syringes 
- 2, 6, 10, 12, 20, 24 and 30 pre-filled syringes with needle guard 

- 2 and 10 pre-filled syringes with UltraSafe Passive needle guard  
 

Inhixa 8,000 IU (80 mg)/0.8 mL is 0.8 mL of solution in: 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 
closed by chlorobutyl rubber stopper and a red polypropylene plunger rod. The syringe can be 

additionally equipped with needle guard; or 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 

closed by chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe 

Passive needle guard. 

 

Supplied in packs of:  

- 2, 6, 10, 30 and 50 pre-filled syringes 
- 2, 6, 10, 12, 24 and 30 pre-filled syringes with needle guard 

- 2 and 10 pre-filled syringes with UltraSafe Passive needle guard  
 

Inhixa 10,000 IU (100 mg)/1 mL is 1 mL of solution in: 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 
closed by chlorobutyl rubber stopper and a black polypropylene plunger rod. The syringe can be 

additionally equipped with needle guard; or 



 

296 

 

- a clear, colourless type I neutral glass graduated syringe barrel with fixed needle and needle shield 

closed by chlorobutyl rubber stopper and a white polycarbonate plunger rod equipped with UltraSafe 

Passive needle guard. 

 

Supplied in packs of:  

- 2, 6, 10, 30, 50 and 90 pre-filled syringes 
- 2, 6, 10, 12, 24 and 30 pre-filled syringes with needle guard 

- 2 and 10 pre-filled syringes with UltraSafe Passive needle guard  
 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 
Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

Manufacturer 

 

Health-Med spółka z ograniczoną odpowiedzialnością sp.k. 

Chełmska 30/34 

00-725 Warsaw 

Poland 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Techdow Pharma Netherlands B.V. 

+31 (0)76 531 5388 

 

Lietuva 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

България 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

Luxembourg/Luxemburg 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Česká republika 
Techdow Pharma Netherlands B.V. 

+420255790502 

Magyarország 

Techdow Pharma Netherlands B.V. 

+3618001930 

Danmark 
Techdow Pharma Netherlands B.V. 

+4578774377  

Malta 

Techdow Pharma England Ltd 

+441483928995 

 

Deutschland 
Mitvertrieb: Techdow Pharma Germany GmbH 

Potsdamer Platz 1, 10785 Berlin 

+49 (0)30 98 321 31 00 

 

Nederland 

Techdow Pharma Netherlands B.V. 

+31208081112 
 

Eesti 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Norge 
Techdow Pharma Netherlands B.V. 

+4781503351 

 

Ελλάδα 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Österreich 
Techdow Pharma Netherlands B.V. 

+43720230772 

 



 

297 

 

España 

TECHDOW PHARMA SPAIN, S.L. 

Tel: +34 91 123 21 16 

Polska 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

France 

MYLAN S.A.S. 

+33 4 37 25 75 00 

 

Portugal 
Laboratórios Atral, S.A. 

+351308801067 

Hrvatska 
Techdow Pharma Netherlands B.V. 

+385 17776255 

 

Ireland 
Techdow Pharma England Ltd 

+441483928995 

 

România 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

Slovenija 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

Ísland 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Slovenská republika 

Techdow Pharma Netherlands B.V. 

+421233331071 

 

Italia 
Techdow Pharma Italy S.R.L. 

Tel: +39 0256569157 

 

Suomi/Finland 
Techdow Pharma Netherlands B.V. 

+358942733040 

Κύπρος 

MA Pharmaceuticals Trading Ltd 

+357 25 587112 

 

Sverige 

Techdow Pharma Netherlands B.V. 

+46184445720 

Latvija 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

United Kingdom 

Techdow Pharma England Ltd 

+441483928995 

 

This leaflet was last revised in  
 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu.  

  

http://www.ema.europa.eu/


 

298 

 

Package leaflet: Information for the user 

 

Inhixa 12,000 IU (120 mg)/0.8 mL solution for injection  

Inhixa 15,000 IU (150 mg)/1 mL solution for injection 

enoxaparin sodium 

 

This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how to 

report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains important 

information for you. 

- Keep this leaflet. You may need to read it again.  

- If you have any further questions, ask your doctor, pharmacist or nurse. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 

their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Inhixa is and what it is used for 

2. What you need to know before you use Inhixa 

3. How to use Inhixa 

4. Possible side effects 

5. How to store Inhixa  

6. Contents of the pack and other information 

 

 

1. What Inhixa is and what it is used for 

 

Inhixa contains the active substance called enoxaparin sodium that is a low molecular weight heparin 

(LMWH). 

 

Inhixa works in two ways. 

1)  Stopping existing blood clots from getting any bigger. This helps your body to break them down and 

stop them causing you harm. 

2)  Stopping blood clots forming in your blood. 

 

Inhixa can be used to: 

 Treat blood clots that are in your blood 

 Stop blood clots from forming in your blood in the following situations: 
o Before and after an operation  
o When you have an acute illness and face period of limited mobility 
o When you have unstable angina (a condition when not enough blood gets to your heart) 
o After a heart attack 

 Stop blood clots forming in the tubes of your dialysis machine (used for people with severe kidney 
problems). 

 

 

2. What you need to know before you use Inhixa 

 

Do not use Inhixa 

 If you are allergic to enoxaparin sodium or any of the other ingredients of this medicine (listed in 
section 6). Signs of an allergic reaction include: rash, swallowing or breathing problems, swelling of 

your lips, face, throat or tongue. 



 

299 

 

 If you are allergic to heparin or other low molecular weight heparins such as nadroparin, tinzaparin or 
dalteparin. 

 If you have had a reaction to heparin that caused a severe drop in the number of your clotting cells 
(platelets) - this reaction is called heparin-induced thrombocytopenia - within the last 100 days or if 

you have antibodies against enoxaparin in your blood. 

 If you are bleeding heavily or have a condition with a high risk of bleeding (such as stomach ulcer, 
recent surgery of the brain or eyes), including recent bleeding stroke. 

 If you are using Inhixa to treat blood clots in your body and going to receive spinal or epidural 
anaesthesia or lumbar puncture within 24 hours. 

 

Warnings and precautions 

Inhixa should not be used interchangeably with other medicines belonging to the group of low molecular 

weight heparins. This is because they are not exactly the same and do not have the same activity and 

instructions for use. 

 

Talk to your doctor or pharmacist before using Inhixa if: 

 you have ever had a reaction to heparin that caused a severe drop in the number of your platelets 

 you are going to receive spinal or epidural anesthesia or lumbar puncture (see Operations and 
Anaesthetics): a delay should be respected between Inhixa use and this procedure. 

 you have had a heart valve fitted 

 you have endocarditis (an infection of the inner lining of the heart) 

 you have history of gastric ulcer 

 you have had a recent stroke  

 you have high blood pressure 

 you have diabetes or  problems with blood vessels in the eye caused by diabetes (called diabetic 
retinopathy)  

 you have had an operation recently on your eyes or brain 

 you are elderly (over 65 years old) and especially if you are over 75 years old 

 you have kidney problems 

 you have liver problems 

 you are underweight or overweight 

 you have high level of potassium in your blood (this may be checked with a blood test) 

 you are currently using medicines which affect bleeding (see section below – Other medicines). 
 

You may have a blood test before you start using this medicine and at intervals while you are using it; this is 

to check the level of the clotting cells (platelets) and potassium in your blood. 

 

Children and adolescents 

The safety and efficacy of Inhixa has not been evaluated in children or adolescents.  

 

Other medicines and Inhixa 

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 

medicines. 

 Warfarin – used for thinning the blood 

 Aspirin (also known as acetylsalicylic acid or ASA), clopidogrel or other medicines used to stop blood 
clots from forming (see also in section 3, “Changing of anticoagulant medicine”) 

 Dextran injection – used as a blood replacer 

 Ibuprofen, diclofenac, ketorolac or other medicines known as non-steroidal anti-inflammatory agents 
which are used to treat pain and swelling in arthritis and other conditions 

 Prednisolone, dexamethasone or other medicines used to treat asthma, rheumatoid arthritis and other 
conditions 

 Medicines which increase potassium level in your blood such as potassium salts, water pills, some 
medicines for heart problems. 

 



 

300 

 

Operations and anaesthetics 

If you are going to have a spinal puncture or an operation where an epidural or spinal anaesthetic is used, tell 

your doctor that you are using Inhixa. See “Do not use Inhixa”. Also, tell your doctor if you have any 

problem with your spine or if you ever had spinal surgery. 

 

Pregnancy and breast-feeding 

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist 

for advice before taking this medicine. 

If you are pregnant and have a mechanical heart valve, you may be at an increased risk of developing blood 

clots. Your doctor should discuss this with you. 

 

If you are breast-feeding or plan to breast-feed, you should ask your doctor for advice before taking this 

medicine. 

 

Driving and using machines 

Inhixa does not affect the ability to drive and operate machinery. 

 

It is advised that the trade name and batch number of the product you are using are recorded by your 

healthcare professional. 

 

Inhixa contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 

 

3. How to use Inhixa 

 

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 

pharmacist if you are not sure. 

 

Having this medicine 

 Your doctor or nurse will normally give you Inhixa. This is because it needs to be given as an 
injection. 

 When you go home, you may need to continue to use Inhixa and give it yourself (see instructions 
below on how to do this). 

 Inhixa is usually given by injection underneath the skin (subcutaneous). 

 Inhixa can be given by injection into your vein (intravenous) after certain types of heart attack or 
operation. 

 Inhixa can be added to the tube leaving the body (arterial line) at the start of the dialysis session. 
Do not inject Inhixa into a muscle. 

 

How much will be given to you 

 Your doctor will decide how much Inhixa to give you. The amount will depend on the reason it is 
being used. 

 If you have problems with your kidneys you may be given a smaller amount of Inhixa. 
 

1. Treating blood clots that are in your blood 

 The usual dose is 150 IU (1.5 mg) for every kilogram of your weight each day or 100 IU (1 mg) for 
every kilogram of your weight twice a day. 

 Your doctor will decide how long you should receive Inhixa. 
 

2. Stopping blood clots forming in your blood in the following situations: 

 Operation or periods of limited mobility due to an illness 

 The dose will depend on how likely you are to develop a clot. You will be given 2,000 IU 
(20 mg) or 4,000 IU (40 mg) of Inhixa each day.  

 If you are going to have an operation your first injection will be usually given 2 hours or 
12 hours before your operation.  



 

301 

 

 If you have restricted mobility due to illness, you will normally be given 4,000 IU (40 mg) of 
Inhixa each day. 

 Your doctor will decide how long you should receive Inhixa. 
 

 After you have had a heart attack 
Inhixa can be used for two different types of heart attack called STEMI (ST segment elevation myocardial 

infarction) or Non STEMI (NSTEMI). The amount of Inhixa given to you will depend on your age and the 

kind of heart attack you have had. 

 

NSTEMI type of heart attack:  

 The usual dose is 100 IU (1 mg) for every kilogram of weight every 12 hours.  

 Your doctor will normally ask you to take aspirin (acetylsalicylic acid) as well. 

 Your doctor will decide how long you should receive Inhixa. 
 

STEMI type of heart attack if you are under 75 years old: 

 An initial dose of 3,000 IU (30 mg) of Inhixa  will be given as injection into your vein. 

 At the same time you will also be given Inhixa as an injection underneath your skin (subcutaneous 
injection). The usual dose is 100 IU (1 mg) for every kilogram of your weight, every 12 hours.  

 Your doctor will normally ask you to take aspirin (acetylsalicylic acid) as well. 

 Your doctor will decide how long you should receive Inhixa. 
 

STEMI type of heart attack if you are 75 years old or older: 

 The usual dose is 75 IU (0.75 mg) for every kilogram of your weight, every 12 hours. 

 The maximum amount of Inhixa given for the first two injections is 7,500 IU (75 mg). 

 Your doctor will decide how long you should receive Inhixa. 
 

For patients have an operation called percutaneous coronary intervention (PCI): 

Depending on when you were last given Inhixa, your doctor may decide to give an additional dose of Inhixa 

before a PCI operation. This is by injection into your vein. 

 

3. Stopping blood clots from forming in the tubes of your dialysis machine 

 The usual dose is 100 IU (1 mg) for every kilogram of your weight. 

 Inhixa is added to the tube leaving the body (arterial line) at the start of the dialysis session. This 
amount is usually enough for a 4-hour session. However, your doctor may give you a further dose of 

50 IU to 100 IU (0.5 to 1 mg) for every kilogram of your weight, if necessary. 

 

How to give yourself an injection of Inhixa 

 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time from 

the right to the left side of your stomach. This medicine should be injected just under the skin on your 

stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 



 

302 

 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from your 

belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection 

 

8)  Remove the needle by pulling it straight out. 

 

 
 

To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Drop the used syringe into the sharps container. Close the container lid tightly and place the container 

out of reach of children. 



 

303 

 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

How to give yourself an injection of Inhixa 

Your pre-filled syringe has a needle guard attached to it in order to protect you from needle stick injury. 

If you are able to give this medicine to yourself, your doctor or nurse will show you how to do this. Do not 

try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your 

doctor or nurse immediately. 

 

Before injecting yourself with Inhixa 

- Check the expiry date on the medicine. Do not use if the date has passed. 

- Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another 

syringe. 

- Do not use this medicine if you notice any change in the appearance of the product. 

- Make sure you know how much you are going to inject. 

- Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, 

oozing or is still painful, if so talk to your doctor or nurse. 

- Decide where you are going to inject the medicine. Change the place where you inject each time 

from the right to the left side of your stomach. This medicine should be injected just under the skin 

on your stomach, but not too near the belly button or any scar tissue (at least 5 cm away from these). 

- The pre-filled syringe is intended for single use only. 

 

Instructions on injecting yourself with Inhixa 

1)  Wash your hands and the area that you will inject with soap and water. Dry them. 

2)  Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going 

to inject. A lounge chair, recliner, or bed propped up with pillows is ideal. 

3)  Choose an area on the right or left side of your stomach. This should be at least 5 cm away from 

your belly button and out towards your sides. 

 

Remember: Do not inject yourself within 5 cm of your belly button or around existing scars or bruises. 

Change the place where you inject between the left and right sides of your stomach, depending on the area 

you were last injected. 

 

4)  Carefully pull off the needle cap from the syringe. Throw away the cap. The syringe is pre-filled and 

ready to use. 

 
Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the 

medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure 

the needle stays clean (sterile). 

 

5)  Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the 

cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin. 

 

Make sure you hold the skin fold throughout the injection. 

 

6)  Hold the syringe so that the needle is pointing downwards (vertically at a 90º angle). Insert the full 

length of the needle into the skin fold. 

 



 

304 

 

 
 

7)  Press down on the plunger with your finger. This will send the medicine into the fatty tissue of the 

stomach. Make sure you hold the skin fold throughout the injection. 

 

8)  Remove the needle by pulling it straight out. Do not release the pressure on the plunger! 

 

 
 

To avoid bruising, do not rub the injection site after you have injected yourself. 
 

9)  Push hard the plunger. The needle guard, which is in the form of a plastic cylinder, will be activated 

automatically and it will completely cover the needle. 

 
10)  Drop the used syringe into the sharps container. Close the container lid tightly and place the 

container out of reach of children. 

 

When the container is full, dispose of it as your doctor or pharmacist has instructed. Do not put it in 

the household rubbish. 

 

Changing of anticoagulant treatment 

- Changing from Inhixa to blood thinners called vitamin-K antagonists (e.g. warfarin) 
Your doctor will request you perform blood tests called INR and tell you when to stop Inhixa 

accordingly. 

 

- Changing from blood thinners called vitamin-K antagonists (e.g. warfarin) to Inhixa   
Stop taking the vitamin-K antagonist. Your doctor will request you perform blood tests called INR and 

tell you when to start Inhixa accordingly. 

 

- Changing from Inhixa to treatment with direct oral anticoagulant 
Stop taking Inhixa. Start taking the direct oral anticoagulant 0-2 hours before the time you would have 

had the next injection, then continue as normal. 

 



 

305 

 

- Changing from treatment with direct oral anticoagulant to Inhixa 
Stop taking direct oral anticoagulant. Do not start treatment with Inhixa until 12 hours after the final 

dose of direct oral anticoagulant. 

 

If you use more Inhixa than you should 

If you think that you have used too much or too little Inhixa, tell your doctor, nurse or pharmacist 

immediately, even if you have no signs of a problem. If a child accidentally injects or swallows Inhixa, take 

them to a hospital causualty department straight away. 

 

If you forget to use Inhixa 

If you forget to give yourself a dose, have it as soon as you remember. Do not give yourself a double dose on 

the same day to make up for a forgotten dose. Keeping a diary will help to make sure you do not miss a dose. 

 

If you stop using Inhixa  

If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse. 

It is important for you to keep having Inhixa injections until your doctor decides to stop them. If you stop, 

you could get a blood clot which can be very dangerous. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them.  

 

Like other similar medicines (medicines to reduce blood clotting), Inhixa may cause bleeding which may 

potentially be life-threatening. In some cases the bleeding may not be obvious. 

 

If you experience any bleeding event that does not stop by itself or if you experience signs of excessive 

bleeding (exceptional weakness, tiredness, paleness, dizziness, headache or unexplained swelling), consult 

your doctor immediately. 

Your doctor may decide to keep you under closer observation or change your medicine. 

 

Stop using Inhixa and talk to a doctor or nurse at once if you get any signs of a severe allergic reaction (such 

as difficulty breathing, swelling of the lips, mouth, throat or eyes). 

 

You should tell your doctor straight away  

 If you have any sign of blockage of a blood vessel by a blood clot such as: 
- cramping pain, redness, warmth, or swelling in one of your legs – these are symptoms of deep 

vein thrombosis 

- breathlessness, chest pain, fainting or coughing up blood – these are symptoms of a pulmonary 
embolism  

 If you have a painful rash of dark red spots under the skin which do not go away when you put 
pressure on them.  

Your doctor may request you perform a blood test to check your platelet count. 

 

Overall list of possible side effects 

Very common (may affect more than 1 in 10 people) 

 Bleeding. 

 Increases in liver enzymes. 
 

Common (may affect up to 1 in 10 people) 

 You bruise more easily than usual. This could be because of a blood problem with low platelet counts. 

 Pink patches on your skin. These are more likely to appear in the area you have been injected with 
Inhixa. 

 Skin rash (hives, urticaria). 

 Itchy red skin. 

 Bruising or pain at the injection site. 

http://www.nhs.uk/Conditions/Deep-vein-thrombosis/Pages/Symptoms.aspx
http://www.nhs.uk/Conditions/Deep-vein-thrombosis/Pages/Symptoms.aspx
http://www.nhs.uk/conditions/shortness-of-breath/Pages/Introduction.aspx
http://www.nhs.uk/conditions/chest-pain/Pages/Introduction.aspx
http://www.nhs.uk/conditions/Fainting/Pages/Introduction.aspx
http://www.nhs.uk/conditions/coughing-up-blood/Pages/Introduction.aspx
http://www.nhs.uk/Conditions/pulmonary-embolism/Pages/Symptoms.aspx
http://www.nhs.uk/Conditions/pulmonary-embolism/Pages/Symptoms.aspx


 

306 

 

 Decreased red blood cell count. 

 High platelet counts in the blood. 

 Headache. 
 

Uncommon (may affect up to 1 in 100 people) 

 Sudden severe headache. This could be a sign of bleeding in the brain.  

 A feeling of tenderness and swelling in your stomach. You may have bleeding in your stomach.  

 Large red irregularly shaped skin lesions with or without blisters. 

 Skin irritation (local irritation). 

 You notice yellowing of your skin or eyes and your urine becomes darker in colour. This could be 
a liver problem. 

 

Rare (may affect up to 1 in 1,000 people) 

 Severe allergic reaction.  The signs may include: a rash, swallowing or breathing problems, swelling 
of your lips, face, throat or tongue. 

 Increased potassium in your blood. This is more likely to happen in people with kidney problems or 
diabetes. Your doctor will be able to check this by carrying out a blood test. 

 An increase in the number of eosinophils in your blood. Your doctor will be able to check this by 
carrying out a blood test. 

 Hair loss.  

 Osteoporosis (a condition where your bones are more likely to break) after long term use. 

 Tingling, numbness and muscular weakness (particularly in the lower part of your body) when you 
have had a spinal puncture or a spinal anaesthetic.  

 Lost of control over your bladder or bowel (so you cannot control when you go to the toilet). 

 Hard mass or lump at the injection site.  
 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed 

in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this medicine. 

 

 

5. How to store Inhixa 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the label and carton. The expiry date refers 

to the last day of that month. 

 

Store below 25 °C. Do not freeze. 

After dilution the solution should be used within 8 hours.  

 

Do not use this medicine if you notice any visible change in the appearance of the solution. 

 

The Inhixa pre-filled syringes are for single dose use only. Discard any unused medicine. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 

away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Inhixa contains 

- The active substance is enoxaparin sodium. 

Each mL contains 150 mg enoxaparin sodium. 

Each pre-filled syringe of 0.8 mL contains 12,000 IU (120 mg) of enoxaparin sodium.  

Each pre-filled syringe of 1 mL contains 15,000 IU (150 mg) of enoxaparin sodium. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

307 

 

 

- The other ingredient is water for injections. 

 

What Inhixa looks like and contents of the pack 

Inhixa 12,000 IU (120 mg)/0.8 mL is 0.8 mL of solution in: 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 
chlorobutyl rubber stopper and a purple polypropylene plunger rod. The syringe can be additionally 

equipped with needle guard. 

 

Supplied in packs of: 

- 2, 10 and 30 pre-filled syringes, 
- 10 and 30 pre-filled syringes with needle guard. 

 

Inhixa 15,000 IU (150 mg)/1 mL is 1 mL of solution in: 

- a clear, colourless type I neutral glass syringe barrel with fixed needle and needle shield closed by 
chlorobutyl rubber stopper and a dark blue polypropylene plunger rod. The syringe can be additionally 

equipped with needle guard. 

 

Supplied in packs of: 

- 2, 10 and 30 pre-filled syringes, 
- 10 and 30 pre-filled syringes with needle guard. 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

Manufacturer 

Health-Med spółka z ograniczoną odpowiedzialnością sp.k. 

Chełmska 30/34 

00-725 Warsaw 

Poland 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Techdow Pharma Netherlands B.V. 

+31 (0)76 531 5388 
 

Lietuva 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

България 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

Luxembourg/Luxemburg 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Česká republika 
Techdow Pharma Netherlands B.V. 

+420255790502 

Magyarország 

Techdow Pharma Netherlands B.V. 

+3618001930 

Danmark 
Techdow Pharma Netherlands B.V. 

+4578774377  

Malta 

Techdow Pharma England Ltd 

+441483928995 

 

Deutschland 
Mitvertrieb: Techdow Pharma Germany GmbH 

Potsdamer Platz 1, 10785 Berlin 

Nederland 

Techdow Pharma Netherlands B.V. 

+31208081112 



 

308 

 

+49 (0)30 98 321 31 00 

 

 

Eesti 

Techdow Pharma Netherlands B.V.  

+49 (0)30 220 13 6906 

Norge 
Techdow Pharma Netherlands B.V. 

+4781503351 

 

Ελλάδα 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Österreich 
Techdow Pharma Netherlands B.V. 

+43720230772 

 

España 

TECHDOW PHARMA SPAIN, S.L. 

Tel: +34 91 123 21 16 

Polska 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

France 

MYLAN S.A.S. 

+33 4 37 25 75 00 

 

Portugal 
Laboratórios Atral, S.A. 

+351308801067 

Hrvatska 
Techdow Pharma Netherlands B.V. 

+385 17776255 

 

Ireland 
Techdow Pharma England Ltd 

+441483928995 

România 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

Slovenija 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

Ísland 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Slovenská republika 

Techdow Pharma Netherlands B.V. 

+421233331071 

 

Italia 
Techdow Pharma Italy S.R.L. 

Tel: +39 0256569157 

Suomi/Finland 
Techdow Pharma Netherlands B.V. 

+358942733040 

 

Κύπρος 

MA Pharmaceuticals Trading Ltd 

+357 25 587112 

 

Sverige 

Techdow Pharma Netherlands B.V. 

+46184445720 

Latvija 

Techdow Pharma Netherlands B.V.  

+49 (0)30 220 13 6906 

United Kingdom 

Techdow Pharma England Ltd 

+441483928995 

 

This leaflet was last revised in  

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. 

  

http://www.ema.europa.eu/


 

309 

 

Package leaflet: Information for the user 

 

Inhixa 30,000 IU (300 mg)/3 mL solution for injection in multidose vial  

Inhixa 50,000 IU (500 mg)/5 mL solution for injection in multidose vial 

Inhixa 100,000 IU (1000 mg)/10 mL solution for injection in multidose vial 

 

enoxaparin sodium 

 

This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how to 

report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains important 

information for you. 

- Keep this leaflet. You may need to read it again.  

- If you have any further questions, ask your doctor, pharmacist or nurse. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 

their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Inhixa is and what it is used for 

2. What you need to know before you use Inhixa 

3. How to use Inhixa 

4. Possible side effects 

5. How to store Inhixa  

6. Contents of the pack and other information 

 

 

1. What Inhixa is and what it is used for 

 

Inhixa contains the active substance called enoxaparin sodium that is a low molecular weight heparin 

(LMWH). 

 

Inhixa works in two ways. 

1)  Stopping existing blood clots from getting any bigger. This helps your body to break them down and 

stop them causing you harm. 

2)  Stopping blood clots forming in your blood. 

 

Inhixa can be used to: 

 Treat blood clots that are in your blood 

 Stop blood clots from forming in your blood in the following situations: 
o Before and after an operation  
o When you have an acute illness and face period of limited mobility 
o When you have unstable angina (a condition when not enough blood gets to your heart) 
o After a heart attack 
Stop blood clots forming in the tubes of your dialysis machine (used for people with severe kidney 

problems). 

 

 



 

310 

 

2. What you need to know before you use Inhixa 

 

Do not use Inhixa 

- if you are allergic to enoxaparin sodium or any of the other ingredients of this medicine (listed in 
section 6). Signs of an allergic reaction include: rash, swallowing or breathing problems, swelling of 

your lips, face, throat or tongue 

- if you are allergic to heparin or other low molecular weight heparins such as nadroparin, tinzaparin or 
dalteparin 

- if you have had a reaction to heparin that caused a severe drop in the number of your clotting cells 
(platelets) - this reaction is called heparin-induced thrombocytopenia - within the last 100 days or if 

you have antibodies against enoxaparin in your blood 

- if you are bleeding heavily or have a condition with a high risk of bleeding (such as stomach ulcer, 
recent surgery of the brain or eyes), including recent bleeding stroke 

- if you are using Inhixa to treat blood clots in your body and going to receive spinal or epidural 
anaesthesia or lumbar puncture within 24 hours 

- if the patient is a premature or newborn baby up to 1 month because of the risk of severe toxicity 
including abnormal respiration (“gasping syndrome”). 

 

Warnings and precautions 

Inhixa should not be used interchangeably with other medicines belonging to the group of low molecular 

weight heparins. This is because they are not exactly the same and do not have the same activity and 

instructions for use. 

 

Talk to your doctor or pharmacist before using Inhixa if: 

 you have ever had a reaction to heparin that caused a severe drop in the number of your platelets 

 you are going to receive spinal or epidural anesthesia or lumbar puncture (see section “Operations and 
Anaesthetics”): a delay should be respected between Inhixa use and this procedure 

 you have had a heart valve fitted 

 you have endocarditis (an infection of the inner lining of the heart) 

 you have history of gastric ulcer 

 you have had a recent stroke  

 you have high blood pressure 

 you have diabetes or  problems with blood vessels in the eye caused by diabetes (called diabetic 
retinopathy)  

 you have had an operation recently on your eyes or brain 

 you are elderly (over 65 years old) and especially if you are over 75 years old 

 you have kidney problems 

 you have liver problems 

 you are underweight or overweight 

 you have high level of potassium in your blood (this may be checked with a blood test) 

 you are currently using medicines which affect bleeding (see section “Other medicines”). 
 

You may have a blood test before you start using this medicine and at intervals while you are using it; this is 

to check the level of the clotting cells (platelets) and potassium in your blood. 

 

Children and adolescents 

The safety and efficacy of Inhixa has not been evaluated in children or adolescents.  

 

Other medicines and Inhixa 

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 

medicines. 

 Warfarin – used for thinning the blood 

 Acetylsalicylic acid (ASA), clopidogrel or other medicines used to stop blood clots from forming (see 
also section 3, “Changing of anticoagulant medicine”) 

 Dextran injection – used as a blood replacer 



 

311 

 

 Ibuprofen, diclofenac, ketorolac or other medicines known as non-steroidal anti-inflammatory agents 
which are used to treat pain and swelling in arthritis and other conditions 

 Prednisolone, dexamethasone or other medicines used to treat asthma, rheumatoid arthritis and other 
conditions 

 Medicines which increase potassium level in your blood such as potassium salts, water pills, some 
medicines for heart problems. 

 

Operations and anaesthetics 

If you are going to have a spinal puncture or an operation where an epidural or spinal anaesthetic is used, tell 

your doctor that you are using Inhixa. See section “Do not use Inhixa”. Also, tell your doctor if you have any 

problem with your spine or if you ever had spinal surgery. 

 

Pregnancy and breast-feeding 

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist 

for advice before using this medicine. 

If you are pregnant and have a mechanical heart valve, you may be at an increased risk of developing blood 

clots. Your doctor should discuss this with you. 

 

If you are breast-feeding or plan to breast-feed, you should ask your doctor for advice before using this 

medicine. 

 

Driving and using machines 

Inhixa does not affect the ability to drive and operate machinery. 

 

It is advised that the trade name and batch number of the product you are using are recorded by your 

healthcare professional. 

 

Inhixa contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dose within the recommended dose range, that 

is to say essentially ‘sodium-free’. 

 

Important information about some of the ingredients of Inhixa  

Inhixa contains benzyl alcohol (45 mg/3 mL; 75 mg/5 mL; 150 mg/10 mL). Benzyl alcohol may cause 

allergic reactions. 

 

Benzyl alcohol has been linked with the risk of severe side effects including breathing problems (called 

“gasping syndrome”) in young children. 

 

Do not give to your newborn baby (up to 4 weeks old), unless recommended by your doctor. Do not use for 

more than a week in young children (less than 3 years old), unless advised by your doctor or pharmacist. 

 

Ask your doctor or pharmacist for advice if you have a liver or kidney disease, or if you are pregnant or 

breast-feeding. This is because large amounts of benzyl alcohol can build-up in your body and may cause 

side effects (called “metabolic acidosis”). 

 

 

3. How to use Inhixa 

 

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 

pharmacist if you are not sure. 

 

Having this medicine 

 Your doctor or nurse will normally give you Inhixa. This is because it needs to be given as an 
injection. 

 When you go home, you may need to continue to use Inhixa and give it yourself. 

 Inhixa is usually given by injection underneath the skin (subcutaneous). 



 

312 

 

 Inhixa can be given by injection into your vein (intravenous) after certain types of heart attack or 
operation. 

 Inhixa can be added to the tube leaving the body (arterial line) at the start of the dialysis session. 
Do not inject Inhixa into a muscle. 

 

How much will be given to you 

 Your doctor will decide how much Inhixa to give you. The amount will depend on the reason it is 
being used. 

 If you have problems with your kidneys you may be given a smaller amount of Inhixa. 
 

1. Treating blood clots that are in your blood 

 The usual dose is 150 IU (1.5 mg) for every kilogram of your weight each day or 100 IU (1 mg) for 
every kilogram of your weight twice a day. 

 Your doctor will decide how long you should receive Inhixa. 
 

2. Stopping blood clots forming in your blood in the following situations: 

Operation or periods of limited mobility due to an illness 

 The dose will depend on how likely you are to develop a clot. You will be given 2,000 IU (20 mg) or 
4,000 IU (40 mg) of Inhixa each day.  

 If you are going to have an operation your first injection will be usually given 2 hours or 12 hours 
before your operation.  

 If you have restricted mobility due to illness, you will normally be given 4,000 IU (40 mg) of Inhixa 
each day. 

 Your doctor will decide how long you should receive Inhixa. 
 

After you have had a heart attack 

Inhixa can be used for two different types of heart attack called STEMI (ST segment elevation myocardial 

infarction) or Non STEMI (NSTEMI). The amount of Inhixa given to you will depend on your age and the 

kind of heart attack you have had. 

 

NSTEMI type of heart attack:  

 The usual dose is 100 IU (1 mg) for every kilogram of weight every 12 hours.  

 Your doctor will normally ask you to take acetylsalicylic acid as well. 

 Your doctor will decide how long you should receive Inhixa. 
 

STEMI type of heart attack if you are under 75 years old: 

 An initial dose of 3,000 IU (30 mg) of Inhixa  will be given as injection into your vein. 

 At the same time you will also be given Inhixa as an injection underneath your skin (subcutaneous 
injection). The usual dose is 100 IU (1 mg) for every kilogram of your weight, every 12 hours.  

 Your doctor will normally ask you to take acetylsalicylic acid as well. 

 Your doctor will decide how long you should receive Inhixa. 
 

STEMI type of heart attack if you are 75 years old or older: 

 The usual dose is 75 IU (0.75 mg) for every kilogram of your weight, every 12 hours. 

 The maximum amount of Inhixa given for the first two injections is 7,500 IU (75 mg). 

 Your doctor will decide how long you should receive Inhixa. 
 

For patients have an operation called percutaneous coronary intervention (PCI): 

Depending on when you were last given Inhixa, your doctor may decide to give an additional dose of Inhixa 

before a PCI operation. This is by injection into your vein. 

 

3. Stopping blood clots from forming in the tubes of your dialysis machine 

 The usual dose is 100 IU (1 mg) for every kilogram of your weight. 



 

313 

 

 Inhixa is added to the tube leaving the body (arterial line) at the start of the dialysis session. This 
amount is usually enough for a 4-hour session. However, your doctor may give you a further dose of 

50 IU to 100 IU (0.5 to 1 mg) for every kilogram of your weight, if necessary. 

 

Changing of anticoagulant treatment 

Changing from Inhixa to blood thinners called vitamin-K antagonists (e.g. warfarin) 

Your doctor will request you perform blood tests called INR and tell you when to stop Inhixa accordingly. 

 

Changing from blood thinners called vitamin-K antagonists (e.g. warfarin) to Inhixa   

Stop taking the vitamin-K antagonist. Your doctor will request you perform blood tests called INR and tell 

you when to start Inhixa accordingly. 

 

Changing from Inhixa to treatment with direct oral anticoagulant 

Stop using Inhixa. Start taking the direct oral anticoagulant 0-2 hours before the time you would have had the 

next injection, then continue as normal. 

 

Changing from treatment with direct oral anticoagulant to Inhixa 

Stop taking direct oral anticoagulant. Do not start treatment with Inhixa until 12 hours after the final dose of 

direct oral anticoagulant. 

 

If you use more Inhixa than you should 

If you think that you have used too much or too little Inhixa, tell your doctor, nurse or pharmacist 

immediately, even if you have no signs of a problem. If a child accidentally injects or swallows Inhixa, take 

them to a hospital causualty department straight away. 

 

If you forget to use Inhixa 
If you forget to give yourself a dose, have it as soon as you remember. Do not give yourself a double dose on 

the same day to make up for a forgotten dose. Keeping a diary will help to make sure you do not miss a dose. 

 

If you stop using Inhixa  

If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse. 

It is important for you to keep having Inhixa injections until your doctor decides to stop them. If you stop, 

you could get a blood clot which can be very dangerous. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Like other similar medicines (medicines to reduce blood clotting), Inhixa may cause bleeding which may 

potentially be life-threatening. In some cases the bleeding may not be obvious. 

 

If you experience any bleeding event that does not stop by itself or if you experience signs of excessive 

bleeding (exceptional weakness, tiredness, paleness, dizziness, headache or unexplained swelling), consult 

your doctor immediately. 

Your doctor may decide to keep you under closer observation or change your medicine. 

 

Stop using Inhixa and talk to a doctor or nurse at once if you get any signs of a severe allergic reaction (such 

as difficulty breathing, swelling of the lips, mouth, throat or eyes). 

 

You should tell your doctor straight away  

 if you have any sign of blockage of a blood vessel by a blood clot such as: 
o cramping pain, redness, warmth, or swelling in one of your legs – these are symptoms of deep 

vein thrombosis 

o breathlessness, chest pain, fainting or coughing up blood – these are symptoms of a pulmonary 
embolism  

http://www.nhs.uk/Conditions/Deep-vein-thrombosis/Pages/Symptoms.aspx
http://www.nhs.uk/Conditions/Deep-vein-thrombosis/Pages/Symptoms.aspx
http://www.nhs.uk/conditions/shortness-of-breath/Pages/Introduction.aspx
http://www.nhs.uk/conditions/chest-pain/Pages/Introduction.aspx
http://www.nhs.uk/conditions/Fainting/Pages/Introduction.aspx
http://www.nhs.uk/conditions/coughing-up-blood/Pages/Introduction.aspx
http://www.nhs.uk/Conditions/pulmonary-embolism/Pages/Symptoms.aspx
http://www.nhs.uk/Conditions/pulmonary-embolism/Pages/Symptoms.aspx


 

314 

 

 if you have a painful rash of dark red spots under the skin which do not go away when you put 
pressure on them.  

Your doctor may request you perform a blood test to check your platelet count. 

 

Overall list of possible side effects 

Very common ( may affect more than 1 in 10 people) 

 Bleeding. 

 Increases in liver enzymes. 
 

Common (may affect up to 1 in 10 people) 

 You bruise more easily than usual. This could be because of a blood problem with low platelet counts. 

 Pink patches on your skin. These are more likely to appear in the area you have been injected with 
Inhixa. 

 Skin rash (hives, urticaria). 

 Itchy red skin. 

 Bruising or pain at the injection site. 

 Decreased red blood cell count. 

 High platelet counts in the blood. 

 Headache. 
 

Uncommon (may affect up to 1 in 100 people) 

 Sudden severe headache. This could be a sign of bleeding in the brain.  

 A feeling of tenderness and swelling in your stomach. You may have bleeding in your stomach.  

 Large red irregularly shaped skin lesions with or without blisters. 

 Skin irritation (local irritation). 

 You notice yellowing of your skin or eyes and your urine becomes darker in colour. This could be 
a liver problem. 

 

Rare (may affect up to 1 in 1,000 people) 

 Severe allergic reaction.  The signs may include: a rash, swallowing or breathing problems, swelling 
of your lips, face, throat or tongue. 

 Increased potassium in your blood. This is more likely to happen in people with kidney problems or 
diabetes. Your doctor will be able to check this by carrying out a blood test. 

 An increase in the number of eosinophils in your blood. Your doctor will be able to check this by 
carrying out a blood test. 

 Hair loss.  

 Osteoporosis (a condition where your bones are more likely to break) after long term use. 

 Tingling, numbness and muscular weakness (particularly in the lower part of your body) when you 
have had a spinal puncture or a spinal anaesthetic.  

 Lost of control over your bladder or bowel (so you cannot control when you go to the toilet). 

 Hard mass or lump at the injection site.  
 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed 

in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine. 

 

 

5. How to store Inhixa 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the label and carton. The expiry date refers 

to the last day of that month. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

315 

 

Store below 25°C. Do not freeze. 

 

After first opening 

 

Chemical and physical in-use stability has been demonstrated for 28 days at 25°C.  

From a microbiological point of view, once opened, the product may be stored for a maximum of 28 days 

below 25°C. Other in-use storage times and conditions are the responsibility of the user. 

 

After dilution with sodium chloride 9 mg/ml (0.9%) solution for infusion or 5% glucose solution for 

injection 

 

Chemical and physical in-use stability has been demonstrated for 8 hours at 25°C.  

From a microbiological point of view, unless the method of dilution precludes the risk of microbial 

contamination, the product should be used immediately. If not used immediately, in-use storage times and 

conditions are the responsibility of user. 

 

Do not use this medicine if you notice any visible change in the appearance of the solution. 

 

Discard any unused medicine. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 

away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Inhixa contains 

- The active substance is enoxaparin sodium. 

Each mL contains 10,000 IU (100 mg) enoxaparin sodium. 

One vial (3.0 mL) contains 30,000 IU (300 mg) enoxaparin sodium.  

One vial (5.0 mL) contains 50,000 IU (500 mg) enoxaparin sodium. 

One vial (10.0 mL) contains 100,000 IU (1000 mg) enoxaparin sodium. 

- The other ingredients are benzyl alcohol (see section 2) and water for injections. 

 

What Inhixa looks like and contents of the pack 

- 3 mL of solution in clear, colourless type I glass vial sealed with rubber injection stopper and white 
aluminium-plastic cap in a cardboard box. 

 

Supplied in packs of 1 vial. 

 

- 5 mL of solution in clear, colourless type I glass vial sealed with rubber injection stopper and grey 
aluminium-plastic cap in a cardboard box. 

 

Supplied in packs of 5 vials. 

 

- 10 mL of solution in clear, colourless type I glass vial sealed with rubber injection stopper and white 
aluminium-plastic cap in a cardboard box. 

 

Supplied in packs of 1 and 5 vials. 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 

Techdow Pharma Netherlands B.V.  

Strawinskylaan 1143, Toren C-11  

1077XX Amsterdam  

Netherlands 

 

Manufacturer 



 

316 

 

Health-Med spółka z ograniczoną odpowiedzialnością sp.k. 

Chełmska 30/34 

00-725 Warsaw 

Poland 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Techdow Pharma Netherlands B.V. 

+31 (0)76 531 5388 

Lietuva 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

България 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

Luxembourg/Luxemburg 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Česká republika 
Techdow Pharma Netherlands B.V. 

+420255790502 

Magyarország 

Techdow Pharma Netherlands B.V. 

+3618001930 

Danmark 
Techdow Pharma Netherlands B.V. 

+4578774377  

Malta 

Techdow Pharma England Ltd 

+441483928995 

 

Deutschland 
Mitvertrieb: Techdow Pharma Germany GmbH 

Potsdamer Platz 1, 10785 Berlin 

+49 (0)30 98 321 31 00 

 

Nederland 
Techdow Pharma Netherlands B.V. 

+31208081112 

Eesti 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Norge 
Techdow Pharma Netherlands B.V. 

+4781503351 

 

Ελλάδα 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Österreich 
Techdow Pharma Netherlands B.V. 

+43720230772 

 

España 

TECHDOW PHARMA SPAIN, S.L. 

Tel: +34 91 123 21 16 

Polska 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

France 

MYLAN S.A.S. 

+33 4 37 25 75 00 

 

Portugal 
Laboratórios Atral, S.A. 

+351308801067 

Hrvatska 
Techdow Pharma Netherlands B.V. 

+385 17776255 

 

Ireland 
Techdow Pharma England Ltd 

+441483928995 

România 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

Slovenija 
Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

 

Ísland 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

Slovenská republika 

Techdow Pharma Netherlands B.V. 

+421233331071 

 



 

317 

 

Italia 
Techdow Pharma Italy S.R.L. 

Tel: +39 0256569157 

 

Suomi/Finland 
Techdow Pharma Netherlands B.V. 

+358942733040 

Κύπρος 

MA Pharmaceuticals Trading Ltd 

+357 25 587112 

Sverige 

Techdow Pharma Netherlands B.V. 

+46184445720 

 

Latvija 

Techdow Pharma Netherlands B.V. 

+49 (0)30 220 13 6906 

United Kingdom 

Techdow Pharma England Ltd 

+441483928995 

 

This leaflet was last revised in  
 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu.  

 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET