Dynastat

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Dynastat 40 mg powder for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each vial contains 40 mg parecoxib (as 42.36 mg parecoxib sodium). After reconstitution, the 

concentration of parecoxib is 20 mg/ml. Each 2 ml of reconstituted powder contains 40 mg of 

parecoxib. 

 

Excipient with known effect  

This medicinal product contains less than 1 mmol sodium (23 mg) per dose. 

 

When reconstituted in sodium chloride 9 mg/ml (0.9%) solution, Dynastat contains approximately 

0.44 mmol of sodium per vial. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder for solution for injection (powder for injection). 

White to off-white powder. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

For the short-term treatment of postoperative pain in adults. 

 

The decision to prescribe a selective cyclooxygenase-2 (COX-2) inhibitor should be based on an 

assessment of the individual patient's overall risks (see sections 4.3 and 4.4). 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), followed 

every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day. 

 

As the cardiovascular risk of COX-2 specific inhibitors may increase with dose and duration of 

exposure, the shortest duration possible and the lowest effective daily dose should be used. There is 

limited clinical experience with Dynastat treatment beyond three days (see section 5.1). 

 

Concomitant use with opioid analgesics 

Opioid analgesics can be used concurrently with parecoxib, dosing as described in the paragraph 

above. In all clinical assessments parecoxib was administered at a fixed time interval whereas the 

opioids were administered on as needed basis. 

 



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Elderly 

No dose adjustment is generally necessary in elderly patients (≥65 years). However, for elderly 

patients weighing less than 50 kg, treatment should be initiated with half the usual recommended 

dose of Dynastat and reduce the maximum daily dose to 40 mg (see section 5.2). 

 

Hepatic impairment 

There is no clinical experience in patients with severe hepatic impairment (Child-Pugh score 10), 

therefore its use is contraindicated in these patients (see sections 4.3 and 5.2). No dosage 

adjustment is generally necessary in patients with mild hepatic impairment (Child-Pugh score 5-6). 

Dynastat should be introduced with caution and at half the usual recommended dose in patients with 

moderate hepatic impairment (Child-Pugh score 7-9) and the maximum daily dose should be 

reduced to 40 mg.  

 

Renal impairment 

In patients with severe renal impairment (creatinine clearance <30 ml/min.) or patients who may be 

predisposed to fluid retention, parecoxib should be initiated at the lowest recommended dose 

(20 mg) and the patient's kidney function should be closely monitored (see sections 4.4 and 5.2). 

On the basis of pharmacokinetics, no dose adjustment is necessary in patients with mild to 

moderate renal impairment (creatinine clearance of 30-80 ml/min.). 

 

Paediatric population 

The safety and efficacy of parecoxib in children under 18 years old have not been established. No 

data are available. Therefore, parecoxib is not recommended in these patients. 

 

Method of administration 

The IV bolus injection may be given rapidly and directly into a vein or into an existing IV line. The 

IM injection should be given slowly and deeply into the muscle. For instructions on reconstitution 

of the medicinal product before administration, see section 6.6. 

 

Precipitation may occur when Dynastat is combined in solution with other medicinal products and 

therefore Dynastat must not be mixed with any other medicinal product, either during reconstitution 

or injection. In those patients where the same IV line is to be used to inject another medicinal 

product, the line must be adequately flushed prior to and after Dynastat injection with a solution of 

known compatibility. 

 

After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into IV 

lines delivering the following: 

 

• sodium chloride 9 mg/ml (0.9%) solution for injection/infusion; 

• glucose 50 mg/ml (5%) solution for infusion; 

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

injection/infusion; 

or 

• Ringer-Lactate solution for injection. 

 

Injection into an IV line delivering glucose 50 mg/ml (5%) in Ringer-Lactate solution for injection, 

or other IV fluids not listed above, is not recommended as this may cause precipitation from 

solution. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 



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History of previous serious allergic drug reaction of any type, especially cutaneous reactions such 

as Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms syndrome 

(DRESS syndrome), toxic epidermal necrolysis, erythema multiforme or patients with known 

hypersensitivity to sulfonamides (see sections 4.4 and 4.8). 

 

Active peptic ulceration or gastrointestinal (GI) bleeding. 

 

Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, 

urticaria or other allergic-type reactions after taking acetylsalicylic acid or nonsteroidal anti-

inflammatory drugs (NSAIDs) including COX-2 inhibitors. 

 

The third trimester of pregnancy and breast-feeding (see sections 4.6 and 5.3). 

 

Severe hepatic impairment (serum albumin <25 g/l or Child-Pugh score  10). 

 

Inflammatory bowel disease. 

 

Congestive heart failure (NYHA II-IV). 

 

Treatment of post-operative pain following coronary artery bypass graft (CABG) surgery (see 

sections 4.8 and 5.1). 

 

Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease. 

 

4.4 Special warnings and precautions for use  

 

Dynastat has been studied in dental, orthopaedic, gynaecologic (principally hysterectomy) and 

coronary artery bypass graft surgery. There is limited experience in other types of surgery, for 

example gastrointestinal or urological surgery (see section 5.1). 

 

Modes of administration other than IV or IM (e.g. intra-articular, intrathecal) have not been studied 

and should not be used. 

 

Because of the possibility for increased adverse reactions at higher doses of parecoxib, other 

COX-2 inhibitors and NSAIDs, patients treated with parecoxib should be reviewed following dose 

increase and, in the absence of an increase in efficacy, other therapeutic options should be 

considered (see section 4.2). There is limited clinical experience with Dynastat treatment beyond 

three days (see section 5.1). 

 

If, during treatment, patients deteriorate in any of the organ system functions  described below, 

appropriate measures should be taken and discontinuation of parecoxib therapy should be 

considered. 

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, and is therefore 

considered essentially ‘sodium- free’. 

 

Cardiovascular 

COX-2 inhibitors have been associated with increased risk of cardiovascular and thrombotic 

adverse events when taken long term. The exact magnitude of the risk associated with a single dose 

has not been determined, nor has the exact duration of therapy associated with increased risk.  

 



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Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, 

diabetes mellitus, smoking) should only be treated with parecoxib after careful consideration (see 

section 5.1). 

 

Appropriate measures should be taken and discontinuation of parecoxib therapy should be 

considered if there is clinical evidence of deterioration in the condition of specific clinical symptoms 

in these patients. Dynastat has not been studied in cardiovascular revascularization procedures other 

than coronary artery bypass graft (CABG) procedures. Studies in types of surgery other than 

CABG procedures included patients with American Society of Anaesthesiology (ASA) Physical 

Status Class I-III only. 

 

Acetylsalicyclic acid and other NSAIDs 

COX-2 inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular 

thrombo-embolic diseases because of their lack of antiplatelet effects. Therefore, antiplatelet 

therapies should not be discontinued (see section 5.1). Caution should be exercised when 

coadministering Dynastat with warfarin and other oral anticoagulants (see section 4.5). The 

concomitant use of parecoxib with other non- acetylsalicylic acid NSAIDs should be avoided. 

 

Dynastat may mask fever and other signs of inflammation (see section 5.1). In isolated cases, an 

aggravation of soft tissue infections has been described in connection with the use of NSAIDs and 

in nonclinical studies with Dynastat (see section 5.3). Caution should be exercised with respect to 

monitoring the incision for signs of infection in surgical patients receiving Dynastat.  

 

Gastrointestinal 

Upper gastrointestinal (GI) complications (perforations, ulcers or bleedings [PUBs]), some of them 

resulting in fatal outcome, have occurred in patients treated with parecoxib. Caution is advised in 

the treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs; 

the elderly, or patients with a prior history of gastrointestinal disease, such as ulceration and GI 

bleeding, or patients using acetylsalicylic acid concomitantly. The NSAIDs class is also associated 

with increased GI complications when coadministered with glucocorticoids, selective serotonin 

reuptake inhibitors, other antiplatelet drugs, other NSAIDs or patients ingesting alcohol. There is 

further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or other 

gastrointestinal complications), when parecoxib is taken concomitantly with acetylsalicylic acid 

(even at low doses). 

 

Skin reactions 

Serious skin reactions, including erythema multiforme, exfoliative dermatitis and Stevens-Johnson 

syndrome (some of them fatal) have been reported through post-marketing surveillance in patients 

receiving parecoxib. Additionally, fatal reports of toxic epidermal necrolysis have been reported 

through postmarketing surveillance in patients receiving valdecoxib (the active metabolite of 

parecoxib) and cannot be ruled out for parecoxib (see section 4.8).  DRESS syndrome may occur 

with parecoxib exposure based on other serious skin reactions reported with celecoxib and 

valdecoxib exposure. Patients appear to be at highest risk for these reactions early in the course of 

therapy; the onset of the reaction occurring in the majority of cases within the first month of 

treatment. 

 

Appropriate measures should be taken by physicians to monitor for any serious skin reactions with 

therapy, e.g. additional patient consultations. Patients should be advised to immediately report any 

emergent skin condition to their physician. 

 

Parecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other 

sign of hypersensitivity. Serious skin reactions are known to occur with NSAIDs including COX-2 

selective inhibitors as well as other medicinal products. However, the reported rate of serious skin 

events appears to be greater for valdecoxib (the active metabolite of parecoxib) as compared to 



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other COX-2 selective inhibitors. Patients with a history of sulfonamide allergy may be at greater 

risk of skin reactions (see section 4.3). Patients without a history of sulfonamide allergy may also 

be at risk for serious skin reactions. 

 

Hypersensitivity 

Hypersensitivity reactions (anaphylaxis and angioedema) have been reported in post-marketing 

experience with valdecoxib and parecoxib (see section 4.8). Some of these reactions have occurred 

in patients with a history of allergic-type reactions to sulfonamides (see section 4.3). Parecoxib 

should be discontinued at the first sign of hypersensitivity. 

 

Cases of severe hypotension shortly following parecoxib administration have been reported in 

postmarketing experience with parecoxib. Some of these cases have occurred without other signs 

of anaphylaxis. The physician should be prepared to treat severe hypotension. 

 

Fluid retention, oedema, renal 

As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention and 

oedema have been observed in some patients taking parecoxib. Therefore, parecoxib should be used 

with caution in patients with compromised cardiac function, preexisting oedema, or other 

conditions predisposing to, or worsened by, fluid retention including those taking diuretic treatment 

or otherwise at risk of hypovolemia. If there is clinical evidence of deterioration in the condition of 

these patients, appropriate measures including discontinuation of parecoxib should be taken. 

 

Acute renal failure has been reported through post-marketing surveillance in patients receiving 

parecoxib (see section 4.8). Since prostaglandin synthesis inhibition may result in deterioration of 

renal function and fluid retention, caution should be observed when administering Dynastat in 

patients with impaired renal function (see section 4.2) or hypertension, or in patients with 

compromised cardiac or hepatic function or other conditions predisposing to fluid retention. 

 

Caution should be used when initiating treatment with Dynastat in patients with dehydration. In this 

case, it is advisable to rehydrate patients first and then start therapy with Dynastat.  

 

Hypertension 

As with all NSAIDs, parecoxib can lead to the onset of new hypertension or worsening of 

pre-existing hypertension, either of which may contribute to the increased incidence of 

cardiovascular events. Parecoxib should be used with caution in patients with hypertension. Blood 

pressure should be monitored closely during the initiation of therapy with parecoxib and throughout 

the course of therapy. If blood pressure rises significantly, alternative treatment should be 

considered. 

 

Hepatic impairment 

Dynastat should be used with caution in patients with moderate hepatic impairment (Child-Pugh 

score 7-9) (see section 4.2). 

 

Use with oral anticoagulants 

The concomitant use of NSAIDs with oral anticoagulants increases the risk of bleeding. Oral 

anticoagulants include warfarin/coumarin-type and novel oral anticoagulants (e.g. apixaban, 

dabigatran, and rivaroxaban) (see section 4.5). 

 

4.5 Interaction with other medicinal products and other forms of interaction  

 

Pharmacodynamic interactions 

Anticoagulant therapy should be monitored, particularly during the first few days after initiating 

Dynastat therapy in patients receiving warfarin or other anticoagulants, since these patients have an 

increased risk of bleeding complications. Therefore, patients receiving oral anticoagulants should be 



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closely monitored for their prothrombin time INR, particularly in the first few days when therapy 

with parecoxib is initiated or the dose of parecoxib is changed (see section 4.4). 

 

Dynastat had no effect on acetylsalicylic acid-mediated inhibition of platelet aggregation or bleeding 

times. Clinical trials indicate that Dynastat can be given with low dose acetylsalicylic acid 

( 325 mg). In the submitted studies, as with other NSAIDs, an increased risk of gastrointestinal 

ulceration or other gastrointestinal complications compared to use of parecoxib alone was shown 

for concomitant administration of low-dose acetylsalicylic acid (see section 5.1). 

 

Coadministration of parecoxib and heparin did not affect the pharmacodynamics of heparin 

(activated partial thromboplastin time) compared to heparin alone. 

 

Inhibition of prostaglandins by NSAIDs, including COX-2 inhibitors, may diminish the effect of 

angiotensin converting enzyme (ACE) inhibitors, angiotensin II antagonists, beta-blockers and 

diuretics. This interaction should be given consideration in patients receiving parecoxib 

concomitantly with ACE-inhibitors, angiotensin II antagonists, beta-blockers and diuretics. 

 

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with 

compromised renal function, coadministration of NSAIDs, including selec tive COX-2 inhibitors, 

with ACE inhibitors or Angiotensin-II antagonists, may result in further deterioration of renal 

function, including possible acute renal failure. These effects are usually reversible. 

 

Therefore, the concomitant administration of these drugs should be done with caution. Patients 

should be adequately hydrated and the need to monitor the renal function should be assessed at the 

beginning of the concomitant treatment and periodically thereafter. 

 

Coadministration of NSAIDs and ciclosporin or tacrolimus has been suggested to increase the 

nephrotoxic effect of ciclosporin and tacrolimus because of NSAID effects on renal prostaglandins. 

Renal function should be monitored when parecoxib and any of these medicinal products are 

coadministered. 

 

Dynastat may be coadministered with opioid analgesics. In clinical trials, the daily requirement for 

PRN opioids was significantly reduced when coadministered with parecoxib.  

 

Effects of other medicinal products on the pharmacokinetics of parecoxib (or its active metabolite 

valdecoxib) 

Parecoxib is rapidly hydrolysed to the active metabolite valdecoxib. In humans, studies 

demonstrated that valdecoxib metabolism is predominantly mediated via CYP3A4 and 2C9 

isozymes. 

 

Plasma exposure (AUC and Cmax) to valdecoxib was increased (62% and 19%, respectively) when 

coadministered with fluconazole (predominantly a CYP2C9 inhibitor), indicating that the dose of 

parecoxib should be reduced in those patients who are receiving fluconazole therapy. 

 

Plasma exposure (AUC and Cmax) to valdecoxib was increased (38% and 24%, respectively) when 

coadministered with ketoconazole (CYP3A4 inhibitor), however, a dosage adjustment should not 

generally be necessary for patients receiving ketoconazole. 

 

The effect of enzyme induction has not been studied. The metabolism of valdecoxib may increase 

when coadministered with enzyme inducers such as rifampicin, phenytoin, carbamazepine or 

dexamethasone. 

 



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Effect of parecoxib (or its active metabolite valdecoxib) on the pharmacokinetics of other medicinal 

products 

Treatment with valdecoxib (40 mg twice daily for 7 days) produced a 3-fold increase in plasma 

concentrations of dextromethorphan (CYP2D6 substrate). Therefore, caution should be observed 

when coadministering Dynastat and medicinal products that are predominantly metabolised by 

CYP2D6 and which have narrow therapeutic margins (e.g. flecainide, propafenone, metoprolol).  

 

Plasma exposure of omeprazole (CYP 2C19 substrate) 40 mg once daily was increased by 46% 

following administration of valdecoxib 40 mg twice daily for 7 days, while the plasma exposure to 

valdecoxib was unaffected. These results indicate that although valdecoxib is not metabolised by 

CYP2C19, it may be an inhibitor of this isoenzyme. Therefore, caution should be observed when 

administering Dynastat with medicinal products known to be substrates of CYP2C19 (e.g. 

phenytoin, diazepam, or imipramine). 

 

In two pharmacokinetic interaction studies in rheumatoid arthritis patients receiving a stable weekly 

methotrexate dose (5-20 mg/week, as a single oral or intramuscular dose), orally administered 

valdecoxib (10 mg twice daily or 40 mg twice daily) had little or no effect on the steady-state 

plasma concentrations of methotrexate. However caution is advised when methotrexate is 

administered concurrently with NSAIDs, because NSAID administration may result in increased 

plasma levels of methotrexate. Adequate monitoring of methotrexate-related toxicity should be 

considered when coadministering parecoxib and methotrexate. 

 

Coadministration of valdecoxib and lithium produced significant decreases in lithium serum 

clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium 

alone. Lithium serum concentration should be monitored closely when initiating or changing 

parecoxib therapy in patients receiving lithium. 

 

Coadministration of valdecoxib with glibenclamide (CYP3A4 substrate) did not affect either the 

pharmacokinetics (exposure) or the pharmacodynamics (blood glucose and insulin levels) of 

glibenclamide. 

 

Injectable anaesthetics 

Coadministration of IV parecoxib 40 mg with propofol (CYP2C9 substrate) or midazolam (CYP3A4 

substrate) did not affect either the pharmacokinetics (metabolism and exposure) or the 

pharmacodynamics (EEG effects, psychomotor tests and waking from sedation) of IV propofol or 

IV midazolam. Additionally, coadministration of valdecoxib had no clinically significant effect on the 

hepatic or intestinal CYP 3A4-mediated metabolism of orally administered midazolam. 

Administration of IV parecoxib 40 mg had no significant effect on the pharmacokinetics of either IV 

fentanyl or IV alfentanil (CYP3A4 substrates). 

 

Inhalation anaesthetics 

No formal interaction studies have been done. In surgery studies in which parecoxib was 

administered pre-operatively, no evidence of pharmacodynamic interaction was observed in patients 

receiving parecoxib and the inhalation anaesthetic agents nitrous oxide and isoflurane (see section 

5.1). 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

Parecoxib is suspected to cause serious birth defects when administered during the last trimester of 

pregnancy because as with other medicinal products known to inhibit prostaglandin, it may cause 

premature closure of the ductus arteriosus or uterine inertia (see sections 4.3, 5.1 and 5.3). 

 



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NSAID use during the second or third trimester of pregnancy may cause foetal renal dysfunction 

which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such 

effects may occur shortly after treatment initiation and are usually reversible. Pregnant women on 

NSAIDs should be closely monitored for amniotic fluid volume. 

 

Dynastat is contraindicated in the third trimester of pregnancy (see section 4.3). 

 

There are no adequate data from the use of parecoxib in pregnant women or during labour. 

However, inhibition of prostaglandin synthesis might adversely affect pregnancy. Data from 

epidemiological studies suggest an increased risk of miscarriage after use of prostaglandin synthesis 

inhibitors in early pregnancy. In animals, administration of prostaglandin synthesis inhibitors, 

including parecoxib, has been shown to result in increased pre- and post-implantation loss and 

embryo-foetal lethality (see sections 5.1 and 5.3). During the first and second trimester of 

pregnancy, Dynastat should not be given unless clearly necessary. 

 

Breast-feeding 

Administration of a single dose of parecoxib to lactating women following caesarean section 

resulted in the transfer of a relatively small amount of parecoxib and its active metabolite valdecoxib 

into human milk, and this resulted in a low relative dose for the infant (approximately 1% of the 

weight-adjusted maternal dose). Dynastat must not be administered to women who breast-feed (see 

section 4.3). 

 

Fertility 

The use of Dynastat, as with any medicinal product known to inhibit cyclooxygenase/prostaglandin 

synthesis, is not recommended in women attempting to conceive (see sections 4.3, 5.1 and 5.3). 

 

Based on the mechanism of action, the use of NSAIDs, may delay or prevent rupture of ovarian 

follicles, which has been associated with reversible infertility in some women. In women who have 

difficulties conceiving or who are undergoing investigation of infertility, withdrawal of NSAIDs, 

including Dynastat should be considered. 

 

4.7 Effects on ability to drive and use machines  

 

Patients who experience dizziness, vertigo or somnolence after receiving Dynastat should refrain 

from driving or operating machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

The most common adverse reaction for Dynastat is nausea. The most serious reactions occur 

uncommonly to rarely, and include cardiovascular events such as myocardial infarction and severe 

hypotension, as well as hypersensitivity events such as anaphylaxis, angioedema and severe skin 

reactions. Following coronary artery bypass graft surgery, patients administered Dynastat have a 

higher risk of adverse reactions such as: cardiovascular/thromboembolic events (including 

myocardial infarction, stroke/TIA, pulmonary embolus, and deep vein thrombosis; see sections 4.3 

and 5.1), deep surgical infections, and sternal wound healing complications. 

 

Tabulated list of adverse reactions 

The following adverse reactions were reported for patients who received parecoxib (N=5,402) in 

28 placebo-controlled clinical trials. Reports from post-marketing experience have been listed as 

“frequency not known” because the respective frequencies cannot be estimated from the available 

data. Within each frequency grouping, adverse reactions are listed using MedDRA terminology and 

presented in order of decreasing seriousness. 



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Adverse Drug Reaction Frequency 

Very Common 

(1/10) 

Common 

(1/100 to 

<1/10) 

Uncommon 

(1/1000 to <1/100) 

Rare (1/10,000 

to <1/1000) 

Not known 

Infections and infestations 

 Pharyngitis, 

alveolar osteitis 

(dry socket) 

Abnormal sternal 

serous wound 

drainage, wound 

infection 

  

Blood and lymphatic system disorders 

 Anaemia 

postoperative 

Thrombocytopenia   

Immune system disorders 

   Anaphylactoid 

reaction 

 

Metabolism and nutrition disorders 

 Hypokalaemia Hyperglycaemia, 

anorexia 

  

Psychiatric disorders 

 Agitation, 

insomnia 

   

Nervous system disorders 

 Hypoaesthesia, 

dizziness  

Cerebrovascular 

disorder 

  

Ear and labyrinth disorders 

  Ear pain   

Cardiac disorders 

  Myocardial 

infarction, 

bradycardia 

 Circulatory 

collapse, 

congestive heart 

failure, 

tachycardia 

Vascular disorders 

 Hypertension, 

hypotension 

Hypertension 

(aggravated), 

orthostatic 

hypotension 

  

Respiratory, thoracic and mediastinal disorders 

 Respiratory 

insufficiency 

Pulmonary 

embolism 

 Dyspnoea 

Gastrointestinal disorders 

Nausea Abdominal pain, 

vomiting, 

constipation, 

dyspepsia, 

flatulence 

Gastroduodenal 

ulceration, 

gastrooesophageal 

reflux disease, dry 

mouth, 

gastrointestinal 

sounds abnormal 

Pancreatitis, 

oesophagitis, 

oedema mouth 

(perioral swelling) 

 



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Adverse Drug Reaction Frequency 

Very Common 

(1/10) 

Common 

(1/100 to 

<1/10) 

Uncommon 

(1/1000 to <1/100) 

Rare (1/10,000 

to <1/1000) 

Not known 

Skin and subcutaneous tissue disorders 

 Pruritus, 

hyperhidrosis 

Ecchymosis, rash, 

urticaria 

 Stevens-Johnson 

syndrome, 

erythema 

multiforme, 

exfoliative 

dermatitis 

Musculoskeletal and connective tissue disorders 

 Back pain Arthralgia   

Renal and urinary disorders 

 Oliguria  Renal failure 

acute 

Renal failure, 

General disorders and administration site conditions 

 Oedema 

peripheral 

Asthenia, injection site 

pain, injection site 

reaction 

 Hypersensitivity 

reactions 

including 

anaphylaxis and 

angioedema 

Investigations 

 Blood 

creatinine 

increased 

Blood CPK 

increased, blood 

LDH increased, 

SGOT increased, 

SGPT increased, 

BUN increased. 

  

Injury, poisoning and procedural complications 

  Post procedural 

complication (skin) 

  

 

Description of selected adverse reactions 

In post-marketing experience, toxic epidermal necrolysis has been reported in association with the 

use of valdecoxib, and cannot be ruled out for parecoxib (see section 4.4). In addition, the 

following rare, serious adverse reactions have been reported in association with the use of NSAIDs 

and cannot be ruled out for Dynastat: bronchospasm and hepatitis.  

 

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 

 

Reporting of overdose with parecoxib has been associated with adverse reactions which have also 

been described with recommended doses of parecoxib. 

 

In case of overdose, patients should be managed by symptomatic and supportive care. Valdecoxib 

is not removed by haemodialysis. Diuresis or alkalisation of urine may not be useful due to high 

protein binding of valdecoxib. 

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


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5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antiinflammatory and antirheumatic products, Coxibs, ATC code: 

M01AH04 

 

Parecoxib is a prodrug of valdecoxib. Valdecoxib is a selective COX-2 inhibitor within the clinical 

dose range. Cyclooxygenase is responsible for generation of prostaglandins. Two isoforms, COX-1 

and COX-2, have been identified. COX-2 is the isoform of the enzyme that has been shown to be 

induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the 

synthesis of prostanoid mediators of pain, inflammation, and fever. COX-2 is also involved in 

ovulation, implantation and closure of the ductus arteriosus, regulation of renal function, and central 

nervous system functions (fever induction, pain perception and cognitive function). It may also play 

a role in ulcer healing. COX-2 has been identified in tissue around gastric ulcers in man but its 

relevance to ulcer healing has not been established. 

 

The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and COX-2 selective 

inhibitors may be of clinical significance in patients at risk of thrombo-embolic reactions. COX-2 

selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) 

prostacyclin without affecting platelet thromboxane. The clinical relevance of these observations 

has not been established. 

 

Parecoxib has been used in a range of major and minor surgeries. The efficacy of Dynastat was 

established in studies of dental, gynaecologic (hysterectomy), orthopaedic (knee and hip 

replacement), and coronary artery bypass graft surgical pain. The first perceptible analgesic effect 

occurred in 7-13 minutes, with clinically meaningful analgesia demonstrated in 23-39 minutes and a 

peak effect within 2 hours following administration of single doses of 40 mg IV or IM Dynastat. 

The magnitude of analgesic effect of the 40 mg dose was comparable with that of ketorolac 60 mg 

IM or ketorolac 30 mg IV. After a single dose, the duration of analgesia was dose and clinical pain 

model dependent, and ranged from 6 to greater than 12 hours. 

 

Use of parecoxib beyond 3 days 

Most trials were designed for dosing of parecoxib up to 3 days. Data from 3 randomised 

placebo-controlled trials, where the protocols allowed treatment of parecoxib for >3 days was 

pooled and analysed. In the pooled analysis of 676 patients, 318 received placebo and 358 received 

parecoxib. Of the patients treated with parecoxib, 317 patients received parecoxib for up to 4 days, 

32 patients for up to 5 days, while only 8 patients were treated for up to 6 days and 1 patient for 7 

or more days. Of the patients treated with placebo, 270 patients received placebo for up to 4 days, 

43 patients for up to 5 days, while only 3 patients were treated for up to 6 days and 2 patients for 7 

or more days. Both groups had similar demographics. The mean (SD) duration of treatment was 

4.1 (0.4) days for parecoxib and 4.2 (0.5) days for placebo, the range was 4-7 days for parecoxib 

and 4-9 days for placebo. The occurrence of adverse events in patients receiving parecoxib for 

4-7 days (median duration 4 days) was low after treatment Day 3 and similar to placebo. 

 

Opioid-sparing effects 

In a placebo-controlled, orthopedic and general surgery study (n =1050), patients received Dynastat 

at an initial parenteral dose of 40 mg IV followed by 20 mg twice daily for a minimum of 72 hours 

in addition to receiving standard care including supplemental patient controlled opioids. The 

reduction in opioid use with Dynastat treatment on Days 2 and 3 was 7.2 mg and 2.8 mg (37% and 

28% respectively).This reduction in opioid use was accompanied by significant reductions in 

patient-reported opioid symptom distress. Added pain relief compared to opioids alone was shown. 



13 

Additional studies in other surgical settings provided similar observations. There are no data 

indicating less overall adverse events associated with the use of parecoxib compared to placebo 

when used in conjunction with opioids. 

 

Gastrointestinal studies 

In short-term studies (7 days), the incidence of endoscopically observed gastroduodenal ulcers or 

erosions in healthy young and elderly ( 65 years) subjects administered Dynastat (5-21%), 

although higher than placebo (5-12%), was statistically significantly lower than the incidence 

observed with NSAIDs (66-90%). 

 

CABG post-operative safety studies 

In addition to routine adverse event reporting, pre-specified event categories, adjudicated by an 

independent expert committee, were examined in two placebo-controlled safety studies in which 

patients received parecoxib for at least 3 days and then were transitioned to oral valdecoxib for a 

total duration of 10-14 days. All patients received standard of care analgesia during treatment. 

Patients received low-dose acetylsalicylic acid prior to randomization and throughout the two CABG 

surgery studies. 

 

The first CABG surgery study evaluated patients treated with IV parecoxib 40 mg bid for a 

minimum of 3 days, followed by treatment with valdecoxib 40 mg bid (parecoxib/valdecoxib group) 

(n=311) or placebo/placebo (n=151) in a 14-day, double-blind placebo-controlled study. Nine pre-

specified adverse event categories were evaluated (cardiovascular thromboembolic events, 

pericarditis, new onset or exacerbation of congestive heart failure, renal failure/dysfunction, upper 

GI ulcer complications, major non-GI bleeds, infections, non-infectious pulmonary complications, 

and death). There was a significantly (p<0.05) greater incidence of cardiovascular/thromboembolic 

events (myocardial infarction, ischemia, cerebrovascular accident, deep vein thrombosis and 

pulmonary embolism) detected in the parecoxib/valdecoxib treatment group compared to the 

placebo/placebo treatment group for the IV dosing period (2.2% and 0.0% respectively) and over 

the entire study period (4.8% and 1.3% respectively). Surgical wound complications (most 

involving the sternal wound) were observed at an increased rate with parecoxib/valdecoxib 

treatment. 

 

In the second CABG surgery study, four pre-specified event categories were evaluated 

(cardiovascular/thromboembolic; renal dysfunction/renal failure; upper GI ulcer/bleeding; surgical 

wound complication). Patients were randomized within 24-hours post-CABG surgery to: parecoxib 

initial dose of 40 mg IV, then 20 mg IV Q12H for a minimum of 3 days followed by valdecoxib PO 

(20 mg Q12H) (n=544) for the remainder of a 10 day treatment period; placebo IV followed by 

valdecoxib PO (n=544); or placebo IV followed by placebo PO (n=548). A significantly (p=0.033) 

greater incidence of events in the cardiovascular/thromboembolic category was detected in the 

parecoxib/valdecoxib treatment group (2.0%) compared to the placebo/placebo treatment group 

(0.5%). Placebo/valdecoxib treatment was also associated with a higher incidence of CV 

thromboembolic events versus placebo treatment, but this difference did not reach statistical 

significance. Three of the six cardiovascular thromboembolic events in the placebo/valdecoxib 

treatment group occurred during the placebo treatment period; these patients did not receive 

valdecoxib. Pre-specified events that occurred with the highest incidence in all three treatment 

groups involved the category of surgical wound complications, including deep surgical infections 

and sternal wound healing events. 

 

There were no significant differences between active treatments and placebo for any of the other 

pre-specified event categories (renal dysfunction/failure, upper GI ulcer complications or surgical 

wound complications). 

 

General surgery 

In a large (N=1050) major orthopedic/general surgery trial, patients received an initial dose of 

parecoxib 40 mg IV, then 20 mg IV Q12H for a minimum of 3 days followed by valdecoxib PO 

(20 mg Q12H) (n=525) for the remainder of a 10 day treatment period, or placebo IV followed by 



14 

placebo PO (n=525). There were no significant differences in the overall safety profile, including 

the four pre-specified event categories described above for the second CABG surgery study, for 

parecoxib/valdecoxib compared to placebo treatment in these post-surgical patients. 

 

Platelet studies 

In a series of small, multiple dose studies in healthy young and elderly subjects, Dynastat 20 mg or 

40 mg twice daily had no effect on platelet aggregation or bleeding compared to placebo. In young 

subjects, Dynastat 40 mg twice daily had no clinically significant effect on acetylsalicylic 

acid-mediated inhibition of platelet function (see section 4.5). 

 

5.2 Pharmacokinetic properties 

 

Following IV or IM injection, parecoxib is rapidly converted to valdecoxib, the pharmacologically 

active substance, by enzymatic hydrolysis in the liver. 

 

Absorption 

Exposure of valdecoxib following single doses of Dynastat, as measured by both the area under the 

plasma concentration vs. time curve (AUC) and peak concentration (Cmax), is approximately linear in 

the range of clinical doses. AUC and Cmax following twice daily administration is linear up to 50 mg 

IV and 20 mg IM. Steady state plasma concentrations of valdecoxib were reached within 4 days 

with twice daily dosing. 

 

Following single IV and IM doses of parecoxib 20 mg, Cmax of valdecoxib is achieved in 

approximately 30 minutes and approximately 1 hour, respectively. Exposure to valdecoxib was 

similar in terms of AUC and Cmax following IV and IM administration. Exposure to parecoxib was 

similar after IV or IM administration in terms of AUC. Average Cmax of parecoxib after IM dosing 

was lower compared to bolus IV dosing, which is attributed to slower extravascular absorption 

after IM administration. These decreases were not considered clinically important since Cmax of 

valdecoxib is comparable after IM and IV parecoxib administration. 

 

Distribution 

The volume of distribution of valdecoxib after its IV administration is approximately 55 litres. 

Plasma protein binding is approximately 98% over the concentration range achieved with the highest 

recommended dose, 80 mg/day. Valdecoxib, but not parecoxib, is extensively partitioned into 

erythrocytes. 

 

Biotransformation 

Parecoxib is rapidly and almost completely converted to valdecoxib and propionic acid in vivo with 

a plasma half-life of approximately 22 minutes. Elimination of valdecoxib is by extensive hepatic 

metabolism involving multiple pathways, including cytochrome P 450 (CYP) 3A4 and CYP2C9 

isoenzymes and glucuronidation (about 20%) of the sulfonamide moiety. A hydroxylated metabolite 

of valdecoxib (via the CYP pathway) has been identified in human plasma that is active as a COX-2 

inhibitor. It represents approximately 10% of the concentration of valdecoxib; because of this 

metabolite’s low concentration, it is not expected to contribute a significant clinical effect after 

administration of therapeutic doses of parecoxib. 

 

Elimination 

Valdecoxib is eliminated via hepatic metabolism with less than 5% unchanged valdecoxib recovered 

in the urine. No unchanged parecoxib is detected in urine and only trace amounts in the faeces. 

About 70% of the dose is excreted in the urine as inactive metabolites. Plasma clearance (CLp) for 

valdecoxib is about 6 l/hr. After IV or IM dosing of parecoxib, the elimination half-life (t1/2) of 

valdecoxib is about 8 hours. 

 



15 

Elderly 

Dynastat has been administered to 335 elderly patients (65-96 years of age) in pharmacokinetic and 

therapeutic trials. In healthy elderly subjects, the apparent oral clearance of valdecoxib was reduced, 

resulting in an approximately 40% higher plasma exposure of valdecoxib compared to healthy young 

subjects. When adjusted for body weight, steady state plasma exposure of valdecoxib was 16% 

higher in elderly females compared to elderly males (see section 4.2). 

 

Renal impairment 

In patients with varying degrees of renal impairment administered 20 mg IV Dynastat, parecoxib 

was rapidly cleared from plasma. Because renal elimination of valdecoxib is not important to its 

disposition, no changes in valdecoxib clearance were found even in patients with severe renal 

impairment or in patients undergoing dialysis (see section 4.2).  

 

Hepatic impairment 

Moderate hepatic impairment did not result in a reduced rate or extent of parecoxib conversion to 

valdecoxib. In patients with moderate hepatic impairment (Child-Pugh score 7-9), treatment should 

be initiated with half the usual recommended dose of Dynastat and the maximum daily dose should 

be reduced to 40 mg since valdecoxib exposures were more than doubled (130%) in these patients. 

Patients with severe hepatic impairment have not been studied and therefore the use of Dynastat in 

patients with severe hepatic impairment is not recommended (see sections 4.2 and 4.3). 

 

5.3 Preclinical safety data 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology or repeated dose toxicity at 2-fold the maximum human exposure to parecoxib. 

However, in the repeated dose toxicity studies in dogs and rats, the systemic exposures to 

valdecoxib (the active metabolite of parecoxib) were approximately 0.8-fold the systemic exposure 

in elderly human subjects at the maximum recommended therapeutic dose of 80 mg daily. Higher 

doses were associated with aggravation and delayed healing of skin infections, an effect probably 

associated with COX-2 inhibition. 

 

In reproduction toxicity tests, the incidence of post-implantation losses, resorptions and foetal body 

weight retardation occurred at doses not producing maternal toxicity in the rabbit studies. No 

effects of parecoxib on male or female fertilities were found in rats.  

 

The effects of parecoxib have not been evaluated in late pregnancy or in the pre- and postnatal 

period. 

 

Parecoxib administered intravenously to lactating rats as a single dose showed concentrations of 

parecoxib, valdecoxib and a valdecoxib active metabolite in milk similar to that of maternal plasma.  

 

The carcinogenic potential of parecoxib has not been evaluated. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Disodium hydrogen phosphate 

Phosphoric acid and/or sodium hydroxide (for pH adjustment).  

 



16 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except for those 

mentioned in section 6.6. 

 

Dynastat and opioids should not be administered together in the same syringe. 

 

Use of Ringer-Lactate solution for injection or glucose 50 mg/ml (5%) in Ringer Lactate solution for 

injection for reconstitution will cause the parecoxib to precipitate from solution and therefore is not 

recommended. 

 

Use of water for injection is not recommended, as the resulting solution is not isotonic. 

 

Dynastat should not be injected into an IV line delivering any other medicinal product. The IV line 

must be adequately flushed prior to and after Dynastat injection with a solution of known 

compatibility (see section 6.6). 

 

Injection into an IV line delivering glucose 50 mg/ml (5%) in Ringer-Lactate solution for injection, 

or other IV fluids not listed in section 6.6, is not recommended as this may cause precipitation from 

solution. 

 

6.3 Shelf life 

 

The shelf life of the unreconstituted product is 3 years. 

 

Chemical and physical in-use stability of the reconstituted solution, which should not be refrigerated 

or frozen, have been demonstrated for up to 24 hours at 25C. Thus, 24 hours should be 

considered the maximum shelf life of the reconstituted product. However, due to the importance of 

microbiological infection risk for injectable products, the reconstituted solution should be used 

immediately unless reconstitution has taken place in controlled and validated aseptic conditions. 

Unless such requirements are met, in-storage times and conditions prior to use are the responsibility 

of the user, and would not normally be longer than 12 hours at 25C. 

 

6.4 Special precautions for storage  

 

This medicinal product does not require any special storage conditions prior to reconstitution. 

 

For storage conditions of the reconstituted medicinal product see section 6.3. 

 

6.5 Nature and contents of container 

 

Type I colourless glass vials (5 ml) with a butyl rubber stopper, sealed with a purple polypropylene 

flip-off cap on the aluminium overseal. 

 

Dynastat is available in packs containing 10 vials. 

 

6.6 Special precautions for disposal and other handling.  

 

Dynastat must be reconstituted before use. Dynastat is preservative free. Aseptic technique is 

required for its preparation. 

 

Reconstitution solvents 

Acceptable solvents for reconstitution of Dynastat are: 

 



17 

• sodium chloride 9 mg/ml (0.9%) solution for injection/infusion 

• glucose 50 mg/ml (5%) solution for infusion 

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

injection/infusion 

 

Reconstitution process 

Use aseptic technique to reconstitute lyophilised parecoxib (as parecoxib). 

Remove the purple flip-off cap to expose the central portion of the rubber stopper of the 40 mg 

parecoxib vial. Withdraw, with a sterile needle and syringe, 2 ml of an acceptable solvent and insert 

the needle through the central portion of the rubber stopper transferring the solvent into the 40 mg 

vial. Dissolve the powder completely using a gentle swirling motion and inspect the reconstituted 

product before use. The entire contents of the vial should be withdrawn for a single administration. 

 

After reconstitution, the liquid should be a clear solution. Dynastat should be inspected visually for 

particulate matter and discoloration prior to administration. The solution should not be used if 

discolored or cloudy, or if particulate matter is observed. Dynastat should be administered within 

24 hours of reconstitution (see section 6.3), or discarded. 

 

The reconstituted product is isotonic. 

 

IV line solution compatibility 

After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into IV 

lines delivering: 

 

• sodium chloride 9 mg/ml (0.9%) solution for injection/infusion; 

• glucose 50 mg/ml (5%) solution for infusion; 

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

injection/infusion; 

 or 

• Ringer-Lactate solution for injection. 

 

For single use only. Any unused medicinal product or waste material should be disposed of in 

accordance with local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/02/209/005 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 22 March 2002 

Date of latest renewal: 24 January 2012 

 



18 

 

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


19 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dynastat 40 mg powder and solvent for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Powder vial: Each vial contains 40 mg parecoxib (as 42.36 mg parecoxib sodium). After 

reconstitution, the concentration of parecoxib is 20 mg/ml. Each 2 ml of reconstituted powder 

contains 40 mg of parecoxib. 

 

Excipient with known effect  

This medicinal product contains less than 1 mmol sodium (23 mg) per dose. 

 

When reconstituted in sodium chloride 9 mg/ml (0.9%) solution, Dynastat contains approximately 

0.44 mmol of sodium per vial. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder and solvent for solution for injection (powder for injection). 

White to off-white powder. 

 

Solvent: clear and colourless solution. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

For the short-term treatment of postoperative pain in adults. 

 

The decision to prescribe a selective cyclooxygenase-2 (COX-2) inhibitor should be based on an 

assessment of the individual patient's overall risks (see sections 4.3 and 4.4). 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), followed 

every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day. 

 

As the cardiovascular risk of COX-2 specific inhibitors may increase with dose and duration of 

exposure, the shortest duration possible and the lowest effective daily dose should be used. There is 

limited clinical experience with Dynastat treatment beyond three days (see section 5.1). 

 

Concomitant use with opioid analgesics 

Opioid analgesics can be used concurrently with parecoxib, dosing as described in the paragraph 

above. In all clinical assessments parecoxib was administered at a fixed time interval whereas the 

opioids were administered on as needed basis. 



20 

 

Elderly 

No dose adjustment is generally necessary in elderly patients (≥65 years). However, for elderly 

patients weighing less than 50 kg, treatment should be initiated with half the usual recommended 

dose of Dynastat and reduce the maximum daily dose to 40 mg (see section 5.2). 

 

Hepatic impairment 

There is no clinical experience in patients with severe hepatic impairment (Child-Pugh score 10), 

therefore its use is contraindicated in these patients (see sections 4.3 and 5.2). No dosage 

adjustment is generally necessary in patients with mild hepatic impairment (Child-Pugh score 5-6). 

Dynastat should be introduced with caution and at half the usual recommended dose in patients with 

moderate hepatic impairment (Child-Pugh score 7-9) and the maximum daily dose should be 

reduced to 40 mg. 

 

Renal impairment 

In patients with severe renal impairment (creatinine clearance <30 ml/min.) or patients who may be 

predisposed to fluid retention, parecoxib should be initiated at the lowest recommended dose 

(20 mg) and the patient's kidney function should be closely monitored (see sections 4.4 and 5.2). 

On the basis of pharmacokinetics, no dose adjustment is necessary in patients with mild to 

moderate renal impairment (creatinine clearance of 30-80 ml/min.). 

 

Paediatric population 

The safety and efficacy of parecoxib in children under 18 years old have not been established. No 

data are available. Therefore, parecoxib is not recommended in these patients. 

 

Method of administration 

The IV bolus injection may be given rapidly and directly into a vein or into an existing IV line. The 

IM injection should be given slowly and deeply into the muscle. For instructions on reconstitution 

of the medicinal product before administration, see section 6.6. 

 

Precipitation may occur when Dynastat is combined in solution with other medicinal products and 

therefore Dynastat must not be mixed with any other medicinal product, either during reconstitution 

or injection. In those patients where the same IV line is to be used to inject another medicinal 

product, the line must be adequately flushed prior to and after Dynastat injection with a solution of 

known compatibility.  

 

After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into IV 

lines delivering the following: 

 

• sodium chloride 9 mg/ml (0.9%) solution for injection/infusion; 

• glucose 50 mg/ml (5%) solution for infusion; 

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

injection/infusion; or 

• Ringer-Lactate solution for injection. 

 

Injection into an IV line delivering glucose 50 mg/ml (5%) in Ringer-Lactate solution for injection, 

or other IV fluids not listed above, is not recommended as this may cause precipitation from 

solution. 

 



21 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

History of previous serious allergic drug reaction of any type, especially cutaneous reactions such 

as Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms syndrome 

(DRESS syndrome), toxic epidermal necrolysis, erythema multiforme or patients with known 

hypersensitivity to sulfonamides (see sections 4.4 and 4.8). 

 

Active peptic ulceration or gastrointestinal (GI) bleeding. 

 

Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, 

urticaria or other allergic-type reactions after taking acetylsalicylic acid or nonsteroidal 

anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors. 

 

The third trimester of pregnancy and breast-feeding (see sections 4.6 and 5.3). 

 

Severe hepatic impairment (serum albumin <25 g/l or Child-Pugh score 10). 

 

Inflammatory bowel disease. 

 

Congestive heart failure (NYHA II-IV). 

 

Treatment of post-operative pain following coronary artery bypass graft (CABG) surgery (see 

sections 4.8 and 5.1). 

 

Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.  

 

4.4 Special warnings and precautions for use  

 

Dynastat has been studied in dental, orthopaedic, gynaecologic (principally hysterectomy) and 

coronary artery bypass graft surgery. There is limited experience in other types of surgery, for 

example gastrointestinal or urological surgery (see section 5.1). 

 

Modes of administration other than IV or IM (e.g. intra-articular, intrathecal) have not been studied 

and should not be used. 

 

Because of the possibility for increased adverse reactions at higher doses of parecoxib, other 

COX-2 inhibitors and NSAIDs, patients treated with parecoxib should be reviewed following dose 

increase and, in the absence of an increase in efficacy, other therapeutic options should be 

considered (see section 4.2). There is limited clinical experience with Dynastat treatment beyond 

three days (see section 5.1). 

 

If, during treatment, patients deteriorate in any of the organ system functions  described below, 

appropriate measures should be taken and discontinuation of parecoxib therapy should be 

considered. 

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, and is therefore 

considered essentially ‘sodium- free’. 

 



22 

Cardiovascular 

COX-2 inhibitors have been associated with increased risk of cardiovascular and thrombotic 

adverse events when taken long term. The exact magnitude of the risk associated with a single dose 

has not been determined, nor has the exact duration of therapy associated with increased risk.  

 

Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, 

diabetes mellitus, smoking) should only be treated with parecoxib after careful consideration (see 

section 5.1). 

 

Appropriate measures should be taken and discontinuation of parecoxib therapy should be 

considered if there is clinical evidence of deterioration in the condition of specific clinical symptoms 

in these patients. Dynastat has not been studied in cardiovascular revascularization procedures other 

than coronary artery bypass graft (CABG) procedures. Studies in types of surgery other than 

CABG procedures included patients with American Society of Anaesthesiology (ASA) Physical 

Status Class I-III only. 

 

Acetylsalicyclic acid and other NSAIDs 

COX-2 inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular 

thrombo-embolic diseases because of their lack of antiplatelet effects. Therefore, antiplatelet 

therapies should not be discontinued (see section 5.1). Caution should be exercised when 

coadministering Dynastat with warfarin and other oral anticoagulants (see section 4.5). The 

concomitant use of parecoxib with other non- acetylsalicylic acid NSAIDs should be avoided. 

 

Dynastat may mask fever and other signs of inflammation (see section 5.1). In isolated cases, an 

aggravation of soft tissue infections has been described in connection with the use of NSAIDs and 

in nonclinical studies with Dynastat (see section 5.3). Caution should be exercised with respect to 

monitoring the incision for signs of infection in surgical patients receiving Dynastat.  

 

Gastrointestinal 

Upper gastrointestinal (GI) complications (perforations, ulcers or bleedings [PUBs]), some of them 

resulting in fatal outcome, have occurred in patients treated with parecoxib. Caution is advised in 

the treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs; 

the elderly, or patients with a prior history of gastrointestinal disease, such as ulceration and GI 

bleeding, or patients using acetylsalicylic acid concomitantly. The NSAIDs class is also associated 

with increased GI complications when coadministered with glucocorticoids, selective serotonin 

reuptake inhibitors, other antiplatelet drugs, other NSAIDs or patients ingesting alcohol. There is 

further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or other 

gastrointestinal complications), when parecoxib is taken concomitantly with acetylsalicylic acid 

(even at low doses). 

 

Skin reactions 

Serious skin reactions, including erythema multiforme, exfoliative dermatitis and Stevens-Johnson 

syndrome (some of them fatal) have been reported through post-marketing surveillance in patients 

receiving parecoxib. Additionally, fatal reports of toxic epidermal necrolysis have been reported 

through postmarketing surveillance in patients receiving valdecoxib (the active metabolite of 

parecoxib) and cannot be ruled out for parecoxib (see section 4.8). DRESS syndrome may occur 

with parecoxib exposure based on other serious skin reactions reported with celecoxib and 

valdecoxib exposure. Patients appear to be at highest risk for these reactions early in the course of 

therapy; the onset of the reaction occurring in the majority of cases within the first month of 

treatment. 

 

Appropriate measures should be taken by physicians to monitor for any serious skin reactions with 

therapy, e.g. additional patient consultations. Patients should be advised to immediately report any 

emergent skin condition to their physician. 

 



23 

Parecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other 

sign of hypersensitivity. Serious skin reactions are known to occur with NSAIDs including COX-2 

selective inhibitors as well as other medicinal products. However, the reported rate of serious skin 

events appears to be greater for valdecoxib (the active metabolite of parecoxib) as compared to 

other COX-2 selective inhibitors. Patients with a history of sulfonamide allergy may be at greater 

risk of skin reactions (see section 4.3). Patients without a history of sulfonamide allergy may also 

be at risk for serious skin reactions. 

 

Hypersensitivity 

Hypersensitivity reactions (anaphylaxis and angioedema) have been reported in post-marketing 

experience with valdecoxib and parecoxib (see section 4.8). Some of these reactions have occurred 

in patients with a history of allergic-type reactions to sulfonamides (see section 4.3). Parecoxib 

should be discontinued at the first sign of hypersensitivity. 

 

Cases of severe hypotension shortly following parecoxib administration have been reported in 

postmarketing experience with parecoxib. Some of these cases have occurred without other signs 

of anaphylaxis. The physician should be prepared to treat severe hypotension. 

 

Fluid retention, oedema, renal 

As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention and 

oedema have been observed in some patients taking parecoxib. Therefore, parecoxib should be used 

with caution in patients with compromised cardiac function, preexisting oedema, or other 

conditions predisposing to, or worsened by, fluid retention including those taking diuretic treatment 

or otherwise at risk of hypovolemia. If there is clinical evidence of deterioration in the condition of 

these patients, appropriate measures including discontinuation of parecoxib should be taken. 

 

Acute renal failure has been reported through post-marketing surveillance in patients receiving 

parecoxib (see section 4.8). Since prostaglandin synthesis inhibition may result in deterioration of 

renal function and fluid retention, caution should be observed when administering Dynastat in 

patients with impaired renal function (see section 4.2) or hypertension, or in patients with 

compromised cardiac or hepatic function or other conditions predisposing to fluid retention.  

 

Caution should be used when initiating treatment with Dynastat in patients with dehydration. In this 

case, it is advisable to rehydrate patients first and then start therapy with Dynastat.  

 

Hypertension 

As with all NSAIDs, parecoxib can lead to the onset of new hypertension or worsening of 

pre-existing hypertension, either of which may contribute to the increased incidence of 

cardiovascular events. Parecoxib should be used with caution in patients with hypertension. Blood 

pressure should be monitored closely during the initiation of therapy with parecoxib and throughout 

the course of therapy. If blood pressure rises significantly, alternative treatment should be 

considered. 

 

Hepatic impairment 

Dynastat should be used with caution in patients with moderate hepatic impairment (Child-Pugh 

score 7-9) (see section 4.2). 

 

Use with oral anticoagulants 

The concomitant use of NSAIDs with oral anticoagulants increases the risk of bleeding. Oral 

anticoagulants include warfarin/coumarin-type and novel oral anticoagulants (e.g. apixaban, 

dabigatran, and rivaroxaban) (see section 4.5). 

 



24 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Pharmacodynamic interactions 

Anticoagulant therapy should be monitored, particularly during the first few days after initiating 

Dynastat therapy in patients receiving warfarin or other anticoagulants, since these patients have an 

increased risk of bleeding complications. Therefore, patients receiving oral anticoagulants should be 

closely monitored for their prothrombin time INR, particularly in the first few days when therapy 

with parecoxib is initiated or the dose of parecoxib is changed (see section 4.4). 

 

Dynastat had no effect on acetylsalicylic acid-mediated inhibition of platelet aggregation or bleeding 

times. Clinical trials indicate that Dynastat can be given with low dose acetylsalicylic acid 

( 325 mg). In the submitted studies, as with other NSAIDs, an increased risk of gastrointestinal 

ulceration or other gastrointestinal complications compared to use of parecoxib alone was  shown 

for concomitant administration of low-dose acetylsalicylic acid (see section 5.1). 

 

Coadministration of parecoxib and heparin did not affect the pharmacodynamics of heparin 

(activated partial thromboplastin time) compared to heparin alone. 

 

Inhibition of prostaglandins by NSAIDs, including COX-2 inhibitors, may diminish the effect of 

angiotensin converting enzyme (ACE) inhibitors, angiotensin II antagonists, beta-blockers and 

diuretics. This interaction should be given consideration in patients receiving parecoxib 

concomitantly with ACE-inhibitors, angiotensin II antagonists, beta-blockers and diuretics. 

 

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with 

compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, 

with ACE inhibitors or Angiotensin-II antagonists, may result in further deterioration of renal 

function, including possible acute renal failure. These effects are usually reversible.  

 

Therefore, the concomitant administration of these drugs should be done with caution. Patients 

should be adequately hydrated and the need to monitor the renal function should be assessed at the 

beginning of the concomitant treatment and periodically thereafter.  

 

Coadministration of NSAIDs and ciclosporin or tacrolimus has been suggested to increase the 

nephrotoxic effect of ciclosporin and tacrolimus because of NSAID effects on renal prostaglandins. 

Renal function should be monitored when parecoxib and any of these medicinal products are 

coadministered. 

 

Dynastat may be coadministered with opioid analgesics. In clinical trials, the daily requirement for 

PRN opioids was significantly reduced when coadministered with parecoxib.  

 

Effects of other medicinal products on the pharmacokinetics of parecoxib (or its active metabolite 

valdecoxib) 

Parecoxib is rapidly hydrolysed to the active metabolite valdecoxib. In humans, studies 

demonstrated that valdecoxib metabolism is predominantly mediated via CYP3A4 and 2C9 

isozymes. 

 

Plasma exposure (AUC and Cmax) to valdecoxib was increased (62% and 19%, respectively) when 

coadministered with fluconazole (predominantly a CYP2C9 inhibitor), indicating that the dose of 

parecoxib should be reduced in those patients who are receiving fluconazole therapy. 

 

Plasma exposure (AUC and Cmax) to valdecoxib was increased (38% and 24%, respectively) when 

coadministered with ketoconazole (CYP3A4 inhibitor), however, a dosage adjustment should not 

generally be necessary for patients receiving ketoconazole. 

 



25 

The effect of enzyme induction has not been studied. The metabolism of valdecoxib may increase 

when coadministered with enzyme inducers such as rifampicin, phenytoin, carbamazepine or 

dexamethasone. 

 

Effect of parecoxib (or its active metabolite valdecoxib) on the pharmacokinetics of other medicinal 

products 

Treatment with valdecoxib (40 mg twice daily for 7 days) produced a 3-fold increase in plasma 

concentrations of dextromethorphan (CYP2D6 substrate). Therefore, caution should be observed 

when coadministering Dynastat and medicinal products that are predominantly metabolised by 

CYP2D6 and which have narrow therapeutic margins (e.g. flecainide, propafenone, metoprolol).  

 

Plasma exposure of omeprazole (CYP 2C19 substrate) 40 mg once daily was increased by 46% 

following administration of valdecoxib 40 mg twice daily for 7 days, while the plasma exposure to 

valdecoxib was unaffected. These results indicate that although valdecoxib is not metabolised by 

CYP2C19, it may be an inhibitor of this isoenzyme. Therefore, caution should be observed when 

administering Dynastat with medicinal products known to be substrates of CYP2C19 (e.g. 

phenytoin, diazepam, or imipramine). 

 

In two pharmacokinetic interaction studies in rheumatoid arthritis patients receiving a stable weekly 

methotrexate dose (5-20 mg/week, as a single oral or intramuscular dose), orally administered 

valdecoxib (10 mg twice daily or 40 mg twice daily) had little or no effect on the steady-state 

plasma concentrations of methotrexate. However caution is advised when methotrexate is 

administered concurrently with NSAIDs, because NSAID administration may result in increased 

plasma levels of methotrexate. Adequate monitoring of methotrexate-related toxicity should be 

considered when coadministering parecoxib and methotrexate. 

 

Coadministration of valdecoxib and lithium produced significant decreases in lithium serum 

clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium 

alone. Lithium serum concentration should be monitored closely when initiating or changing 

parecoxib therapy in patients receiving lithium. 

 

Coadministration of valdecoxib with glibenclamide (CYP3A4 substrate) did not affect either the 

pharmacokinetics (exposure) or the pharmacodynamics (blood glucose and insulin levels) of 

glibenclamide. 

 

Injectable anaesthetics 

Coadministration of IV parecoxib 40 mg with propofol (CYP2C9 substrate) or midazolam (CYP3A4 

substrate) did not affect either the pharmacokinetics (metabolism and exposure) or the 

pharmacodynamics (EEG effects, psychomotor tests and waking from sedation) of IV propofol or 

IV midazolam. Additionally, coadministration of valdecoxib had no clinically significant effect on the 

hepatic or intestinal CYP 3A4-mediated metabolism of orally administered midazolam. 

Administration of IV parecoxib 40 mg had no significant effect on the pharmacokinetics of either IV 

fentanyl or IV alfentanil (CYP3A4 substrates). 

 

Inhalation anaesthetics 

No formal interaction studies have been done. In surgery studies in which parecoxib was 

administered pre-operatively, no evidence of pharmacodynamic interaction was observed in patients 

receiving parecoxib and the inhalation anaesthetic agents nitrous oxide and isoflurane (see section 

5.1). 

 



26 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

Parecoxib is suspected to cause serious birth defects when administered during the last trimester of 

pregnancy because as with other medicinal products known to inhibit prostaglandin, it may cause 

premature closure of the ductus arteriosus or uterine inertia (see sections 4.3, 5.1 and 5.3). 

 

NSAID use during the second or third trimester of pregnancy may cause foetal renal dysfunction 

which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such 

effects may occur shortly after treatment initiation and are usually reversible. Pregnant women on 

NSAIDs should be closely monitored for amniotic fluid volume. 

 

Dynastat is contraindicated in the third trimester of pregnancy (see section 4.3). 

 

There are no adequate data from the use of parecoxib in pregnant women or during labour. 

However, inhibition of prostaglandin synthesis might adversely affect pregnancy. Data from 

epidemiological studies suggest an increased risk of miscarriage after use of prostaglandin synthesis 

inhibitors in early pregnancy. In animals, administration of prostaglandin synthesis inhibitors, 

including parecoxib, has been shown to result in increased pre- and post-implantation loss and 

embryo-foetal lethality (see sections 5.1 and 5.3). During the first and second trimester of 

pregnancy, Dynastat should not be given unless clearly necessary. 

 

Breast-feeding 

Administration of a single dose of parecoxib to lactating women following caesarean section 

resulted in the transfer of a relatively small amount of parecoxib and its active metabolite valdecoxib 

into human milk, and this resulted in a low relative dose for the infant (approximately 1% of the 

weight-adjusted maternal dose). Dynastat must not be administered to women who breast-feed (see 

section 4.3). 

 

Fertility 

The use of Dynastat, as with any medicinal product known to inhibit cyclooxygenase/prostaglandin 

synthesis, is not recommended in women attempting to conceive (see sections 4.3, 5.1 and 5.3). 

 

Based on the mechanism of action, the use of NSAIDs, may delay or prevent rupture of ovarian 

follicles, which has been associated with reversible infertility in some women. In women who have 

difficulties conceiving or who are undergoing investigation of infertility, withdrawal of NSAIDs, 

including Dynastat should be considered. 

 

4.7 Effects on ability to drive and use machines  

 

Patients who experience dizziness, vertigo or somnolence after receiving Dynastat should refrain 

from driving or operating machines. 

 



27 

4.8 Undesirable effects 

 

Summary of the safety profile 

The most common adverse reaction for Dynastat is nausea. The most serious reactions occur 

uncommonly to rarely, and include cardiovascular events such as myocardial infarction and severe 

hypotension, as well as hypersensitivity events such as anaphylaxis, angioedema and severe skin 

reactions. Following coronary artery bypass graft surgery, patients administered Dynastat have a 

higher risk of adverse reactions such as: cardiovascular/thromboembolic events (including 

myocardial infarction, stroke/TIA, pulmonary embolus, and deep vein thrombosis; see sections 4.3 

and 5.1), deep surgical infections, and sternal wound healing complications. 

 

Tabulated list of adverse reactions 

The following adverse reactions were reported for patients who received parecoxib (N=5,402) in 

28 placebo-controlled clinical trials. Reports from post-marketing experience have been listed as 

“frequency not known” because the respective frequencies cannot be estimated from the available 

data. Within each frequency grouping, adverse reactions are listed using MedDRA terminology and 

presented in order of decreasing seriousness. 

 

Adverse Drug Reaction Frequency 

Very Common 

(1/10) 

Common 

(1/100 to 

<1/10) 

Uncommon 

(1/1000 to <1/100) 

Rare (1/10,000 

to <1/1000) 

Not known 

Infections and infestations 

 Pharyngitis, 

alveolar osteitis 

(dry socket) 

Abnormal sternal 

serous wound 

drainage, wound 

infection 

  

Blood and lymphatic system disorders 

 Anaemia 

postoperative 

Thrombocytopenia   

Immune system disorders 

   Anaphylactoid 

reaction 

 

Metabolism and nutrition disorders 

 Hypokalaemia Hyperglycaemia, 

anorexia 

  

Psychiatric disorders 

 Agitation, 

insomnia 

   

Nervous system disorders 

 Hypoaesthesia, 

dizziness  

Cerebrovascular 

disorder 

  

Ear and labyrinth disorders 

  Ear pain   

Cardiac disorders 

  Myocardial 

infarction, 

bradycardia 

 Circulatory 

collapse, 

congestive heart 

failure, 

tachycardia 



28 

Adverse Drug Reaction Frequency 

Very Common 

(1/10) 

Common 

(1/100 to 

<1/10) 

Uncommon 

(1/1000 to <1/100) 

Rare (1/10,000 

to <1/1000) 

Not known 

Vascular disorders 

 Hypertension, 

hypotension 

Hypertension 

(aggravated), 

orthostatic 

hypotension 

  

Respiratory, thoracic and mediastinal disorders 

 Respiratory 

insufficiency 

Pulmonary 

embolism 

 Dyspnoea 

Gastrointestinal disorders 

Nausea Abdominal pain, 

vomiting, 

constipation, 

dyspepsia, 

flatulence 

Gastroduodenal 

ulceration, 

gastrooesophageal 

reflux disease, dry 

mouth, 

gastrointestinal 

sounds abnormal 

Pancreatitis, 

oesophagitis, 

oedema mouth 

(perioral swelling) 

 

Skin and subcutaneous tissue disorders 

 Pruritus, 

hyperhidrosis 

Ecchymosis, rash, 

urticaria 

 Stevens-Johnson 

syndrome, 

erythema 

multiforme, 

exfoliative 

dermatitis 

Musculoskeletal and connective tissue disorders 

 Back pain Arthralgia   

Renal and urinary disorders 

 Oliguria  Renal failure 

acute 

Renal failure, 

General disorders and administration site conditions 

 Oedema 

peripheral 

Asthenia, injection site 

pain, injection site 

reaction 

 Hypersensitivity 

reactions 

including 

anaphylaxis and 

angioedema 

Investigations 

 Blood 

creatinine 

increased 

Blood CPK 

increased, blood 

LDH increased, 

SGOT increased, 

SGPT increased, 

BUN increased. 

  

Injury, poisoning and procedural complications 

  Post procedural 

complication (skin) 

  

 

Description of selected adverse reactions 

In post-marketing experience, toxic epidermal necrolysis has been reported in association with the 

use of valdecoxib, and cannot be ruled out for parecoxib (see section 4.4). In addition, the 



29 

following rare, serious adverse reactions have been reported in association with the use of NSAIDs 

and cannot be ruled out for Dynastat: bronchospasm and hepatitis.  

 

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 

 

Reporting of overdose with parecoxib has been associated with adverse reactions which have also 

been described with recommended doses of parecoxib. 

 

In case of overdose, patients should be managed by symptomatic and supportive care. Valdecoxib 

is not removed by haemodialysis. Diuresis or alkalisation of urine may not be useful due to high 

protein binding of valdecoxib. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antiinflammatory and antirheumatic products, Coxibs, ATC code: 

M01AH04 

 

Parecoxib is a prodrug of valdecoxib. Valdecoxib is a selective COX-2 inhibitor within the clinical 

dose range. Cyclooxygenase is responsible for generation of prostaglandins. Two isoforms, COX-1 

and COX-2, have been identified. COX-2 is the isoform of the enzyme that has been shown to be 

induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the 

synthesis of prostanoid mediators of pain, inflammation, and fever. COX-2 is also involved in 

ovulation, implantation and closure of the ductus arteriosus, regulation of renal function, and central 

nervous system functions (fever induction, pain perception and cognitive function). It may also play 

a role in ulcer healing. COX-2 has been identified in tissue around gastric ulcers in man but its 

relevance to ulcer healing has not been established. 

 

The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and COX-2 selective 

inhibitors may be of clinical significance in patients at risk of thrombo-embolic reactions. COX-2 

selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) 

prostacyclin without affecting platelet thromboxane. The clinical relevance of these observations 

has not been established. 

 

Parecoxib has been used in a range of major and minor surgeries. The efficacy of Dynastat was 

established in studies of dental, gynaecologic (hysterectomy), orthopaedic (knee and hip 

replacement), and coronary artery bypass graft surgical pain. The first perceptible analgesic effect 

occurred in 7-13 minutes, with clinically meaningful analgesia demonstrated in 23-39 minutes and a 

peak effect within 2 hours following administration of single doses of 40 mg IV or IM Dynastat. 

The magnitude of analgesic effect of the 40 mg dose was comparable with that of ketorolac 60 mg 

IM or ketorolac 30 mg IV. After a single dose, the duration of analgesia was dose and clinical pain 

model dependent, and ranged from 6 to greater than 12 hours. 

 

Use of parecoxib beyond 3 days 

Most trials were designed for dosing of parecoxib up to 3 days. Data from 3 randomised 

placebo-controlled trials, where the protocols allowed treatment of parecoxib for >3 days was 

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


30 

pooled and analysed. In the pooled analysis of 676 patients, 318 received placebo and 358 received 

parecoxib. Of the patients treated with parecoxib, 317 patients received parecoxib for up to 4 days, 

32 patients for up to 5 days, while only 8 patients were treated for up to 6 days and 1 patient for 7 

or more days. Of the patients treated with placebo, 270 patients received placebo for up to 4 days, 

43 patients for up to 5 days, while only 3 patients were treated for up to 6 days and 2 patients for 7 

or more days. Both groups had similar demographics. The mean (SD) duration of treatment was 

4.1 (0.4) days for parecoxib and 4.2 (0.5) days for placebo, the range was 4-7 days for parecoxib 

and 4-9 days for placebo. The occurrence of adverse events in patients receiving parecoxib for 

4-7 days (median duration 4 days) was low after treatment Day 3 and similar to placebo. 

 

Opioid-sparing effects 

In a placebo-controlled, orthopedic and general surgery study (n =1050), patients received Dynastat 

at an initial parenteral dose of 40 mg IV followed by 20 mg twice daily for a minimum of 72 hours 

in addition to receiving standard care including supplemental patient controlled opioids. The 

reduction in opioid use with Dynastat treatment on Days 2 and 3 was 7.2 mg and 2.8 mg (37% and 

28% respectively).This reduction in opioid use was accompanied by significant reductions in 

patient-reported opioid symptom distress. Added pain relief compared to opioids alone was shown. 

Additional studies in other surgical settings provided similar observations.  There are no data 

indicating less overall adverse events associated with the use of parecoxib compared to placebo 

when used in conjunction with opioids. 

 

Gastrointestinal studies 

In short-term studies (7 days), the incidence of endoscopically observed gastroduodenal ulcers or 

erosions in healthy young and elderly ( 65 years) subjects administered Dynastat (5-21%), 

although higher than placebo (5-12%), was statistically significantly lower than the incidence 

observed with NSAIDs (66-90%). 

 

CABG post-operative safety studies 

In addition to routine adverse event reporting, pre-specified event categories, adjudicated by an 

independent expert committee, were examined in two placebo-controlled safety studies in which 

patients received parecoxib for at least 3 days and then were transitioned to oral valdecoxib for a 

total duration of 10-14 days. All patients received standard of care analgesia during treatment. 

Patients received low-dose acetylsalicylic acid prior to randomization and throughout the two CABG 

surgery studies. 

 

The first CABG surgery study evaluated patients treated with IV parecoxib 40 mg bid for a 

minimum of 3 days, followed by treatment with valdecoxib 40 mg bid (parecoxib/valdecoxib group) 

(n=311) or placebo/placebo (n=151) in a 14-day, double-blind placebo-controlled study. Nine pre-

specified adverse event categories were evaluated (cardiovascular thromboembolic events, 

pericarditis, new onset or exacerbation of congestive heart failure, renal failure/dysfunction, upper 

GI ulcer complications, major non-GI bleeds, infections, non-infectious pulmonary complications, 

and death). There was a significantly (p<0.05) greater incidence of cardiovascular/thromboembolic 

events (myocardial infarction, ischemia, cerebrovascular accident, deep vein thrombosis and 

pulmonary embolism) detected in the parecoxib/valdecoxib treatment group compared to the 

placebo/placebo treatment group for the IV dosing period (2.2% and 0.0% respectively) and over 

the entire study period (4.8% and 1.3% respectively). Surgical wound complications (most 

involving the sternal wound) were observed at an increased rate with parecoxib/valdecoxib 

treatment. 

 

In the second CABG surgery study, four pre-specified event categories were evaluated 

(cardiovascular/thromboembolic; renal dysfunction/renal failure; upper GI ulcer/bleeding; surgical 

wound complication). Patients were randomized within 24-hours post-CABG surgery to: parecoxib 

initial dose of 40 mg IV, then 20 mg IV Q12H for a minimum of 3 days followed by valdecoxib PO 

(20 mg Q12H) (n=544) for the remainder of a 10 day treatment period; placebo IV followed by 

valdecoxib PO (n=544); or placebo IV followed by placebo PO (n=548). A significantly (p=0.033) 



31 

greater incidence of events in the cardiovascular/thromboembolic category was detected in the 

parecoxib/valdecoxib treatment group (2.0%) compared to the placebo/placebo treatment group 

(0.5%). Placebo/valdecoxib treatment was also associated with a higher incidence of CV 

thromboembolic events versus placebo treatment, but this difference did not reach statistical 

significance. Three of the six cardiovascular thromboembolic events in the placebo/valdecoxib 

treatment group occurred during the placebo treatment period; these patients did not receive 

valdecoxib. Pre-specified events that occurred with the highest incidence in all three treatment 

groups involved the category of surgical wound complications, including deep surgical infections 

and sternal wound healing events. 

 

There were no significant differences between active treatments and placebo for any of the other 

pre-specified event categories (renal dysfunction/failure, upper GI ulcer complications or surgical 

wound complications). 

 

General surgery 

In a large (N=1050) major orthopedic/general surgery trial, patients received an initial dose of 

parecoxib 40 mg IV, then 20 mg IV Q12H for a minimum of 3 days followed by valdecoxib PO 

(20 mg Q12H) (n=525) for the remainder of a 10 day treatment period, or placebo IV followed by 

placebo PO (n=525). There were no significant differences in the overall safety profile, including 

the four pre-specified event categories described above for the second CABG surgery study, for 

parecoxib/valdecoxib compared to placebo treatment in these post-surgical patients. 

 

Platelet studies 

In a series of small, multiple dose studies in healthy young and elderly subjects, Dynastat 20 mg or 

40 mg twice daily had no effect on platelet aggregation or bleeding compared to placebo.  In young 

subjects, Dynastat 40 mg twice daily had no clinically significant effect on acetylsalicylic 

acid-mediated inhibition of platelet function (see section 4.5). 

 

5.2 Pharmacokinetic properties 

 

Following IV or IM injection, parecoxib is rapidly converted to valdecoxib,  the pharmacologically 

active substance, by enzymatic hydrolysis in the liver. 

 

Absorption 

Exposure of valdecoxib following single doses of Dynastat, as measured by both the area under the 

plasma concentration vs. time curve (AUC) and peak concentration (Cmax), is approximately linear in 

the range of clinical doses. AUC and Cmax following twice daily administration is linear up to 50 mg 

IV and 20 mg IM. Steady state plasma concentrations of valdecoxib were reached within 4 days 

with twice daily dosing. 

 

Following single IV and IM doses of parecoxib 20 mg, Cmax of valdecoxib is achieved in 

approximately 30 minutes and approximately 1 hour, respectively. Exposure to valdecoxib was 

similar in terms of AUC and Cmax following IV and IM administration. Exposure to parecoxib was 

similar after IV or IM administration in terms of AUC. Average Cmax of parecoxib after IM dosing 

was lower compared to bolus IV dosing, which is attributed to slower extravascular absorption 

after IM administration. These decreases were not considered clinically important since Cmax of 

valdecoxib is comparable after IM and IV parecoxib administration. 
 

Distribution 

The volume of distribution of valdecoxib after its IV administration is approximately 55 litres. 

Plasma protein binding is approximately 98% over the concentration range achieved with the highest 

recommended dose, 80 mg/day. Valdecoxib, but not parecoxib, is extensively partitioned into 

erythrocytes. 

 



32 

Biotransformation 

Parecoxib is rapidly and almost completely converted to valdecoxib and propionic acid in vivo with 

a plasma half-life of approximately 22 minutes. Elimination of valdecoxib is by extensive hepatic 

metabolism involving multiple pathways, including cytochrome P 450 (CYP) 3A4 and CYP2C9 

isoenzymes and glucuronidation (about 20%) of the sulfonamide moiety. A hydroxylated metabolite 

of valdecoxib (via the CYP pathway) has been identified in human plasma that is active as a COX-2 

inhibitor. It represents approximately 10% of the concentration of valdecoxib; because of this 

metabolite’s low concentration, it is not expected to contribute a significant clinical effect after 

administration of therapeutic doses of parecoxib. 

 

Elimination 

Valdecoxib is eliminated via hepatic metabolism with less than 5% unchanged valdecoxib recovered 

in the urine. No unchanged parecoxib is detected in urine and only trace amounts in the faeces. 

About 70% of the dose is excreted in the urine as inactive metabolites. Plasma clearance (CLp) for 

valdecoxib is about 6 l/hr. After IV or IM dosing of parecoxib, the elimination half-life (t1/2) of 

valdecoxib is about 8 hours. 

 

Elderly 

Dynastat has been administered to 335 elderly patients (65-96 years of age) in pharmacokinetic and 

therapeutic trials. In healthy elderly subjects, the apparent oral clearance of valdecoxib was reduced, 

resulting in an approximately 40% higher plasma exposure of valdecoxib compared to healthy young 

subjects. When adjusted for body weight, steady state plasma exposure of valdecoxib was 16% 

higher in elderly females compared to elderly males (see section 4.2). 

 

Renal impairment 

In patients with varying degrees of renal impairment administered 20 mg IV Dynastat, parecoxib 

was rapidly cleared from plasma. Because renal elimination of valdecoxib is not important to its 

disposition, no changes in valdecoxib clearance were found even in patients with severe renal 

impairment or in patients undergoing dialysis (see section 4.2). 

 

Hepatic impairment 

Moderate hepatic impairment did not result in a reduced rate or extent of parecoxib conversion to 

valdecoxib. In patients with moderate hepatic impairment (Child-Pugh score 7-9), treatment should 

be initiated with half the usual recommended dose of Dynastat and the maximum daily dose should 

be reduced to 40 mg since valdecoxib exposures were more than doubled (130%) in these patients. 

Patients with severe hepatic impairment have not been studied and therefore the use of Dynastat in 

patients with severe hepatic impairment is not recommended (see sections 4.2 and 4.3). 

 

5.3 Preclinical safety data 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology or repeated dose toxicity at 2-fold the maximum human exposure to parecoxib. 

However, in the repeated dose toxicity studies in dogs and rats, the systemic exposures to 

valdecoxib (the active metabolite of parecoxib) were approximately 0.8-fold the systemic exposure 

in elderly human subjects at the maximum recommended therapeutic dose of 80 mg daily. Higher 

doses were associated with aggravation and delayed healing of skin infections, an effect probably 

associated with COX-2 inhibition. 

 

In reproduction toxicity tests, the incidence of post-implantation losses, resorptions and foetal body 

weight retardation occurred at doses not producing maternal toxicity in the rabbit studies. No 

effects of parecoxib on male or female fertilities were found in rats. 

 



33 

The effects of parecoxib have not been evaluated in late pregnancy or in the pre- and postnatal 

period. 

 

Parecoxib administered intravenously to lactating rats as a single dose showed concentrations of 

parecoxib, valdecoxib and a valdecoxib active metabolite in milk similar to that of maternal plasma. 

 

The carcinogenic potential of parecoxib has not been evaluated. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Powder 

Disodium hydrogen phosphate 

Phosphoric acid and/or sodium hydroxide (for pH adjustment). 

 

Solvent 

Sodium chloride 

Hydrochloric acid or sodium hydroxide (for pH adjustment) 

Water for injection. 

 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except for those 

mentioned in section 6.6. 

 

Dynastat and opioids should not be administered together in the same syringe.  

 

Use of Ringer-Lactate solution for injection or glucose 50 mg/ml (5%) in Ringer Lactate solution for 

injection for reconstitution will cause the parecoxib to precipitate from solution and therefore is not 

recommended. 

 

Use of water for injection is not recommended, as the resulting solution is not isotonic. 

 

Dynastat should not be injected into an IV line delivering any other medicinal product. The IV line 

must be adequately flushed prior to and after Dynastat injection with a solution of known 

compatibility (see section 6.6). 

 

Injection into an IV line delivering glucose 50 mg/ml (5%) in Ringer-Lactate solution for injection, 

or other IV fluids not listed in section 6.6, is not recommended as this may cause precipitation from 

solution. 

 

6.3 Shelf life 

 

The shelf life of the unreconstituted product is 3 years. 

 

Chemical and physical in-use stability of the reconstituted solution, which should not be refrigerated 

or frozen, have been demonstrated for up to 24 hours at 25C. Thus, 24 hours should be 

considered the maximum shelf life of the reconstituted product. However, due to the importance of 

microbiological infection risk for injectable products, the reconstituted solution should be used 

immediately unless reconstitution has taken place in controlled and validated aseptic conditions. 

Unless such requirements are met, in-storage times and conditions prior to use are the responsibility 

of the user, and would not normally be longer than 12 hours at 25C. 



34 

 

6.4 Special precautions for storage  

 

This medicinal product does not require any special storage conditions prior to reconstitution. 

 

For storage conditions of the reconstituted medicinal product see section 6.3. 

 

6.5 Nature and contents of container 

 

Parecoxib sodium vials 

Type I colourless glass vials (5 ml) with a butyl rubber stopper, sealed with a purple polypropylene 

flip-off cap on the aluminium overseal. 

 

Solvent ampoules 

2 ml ampoule: colourless neutral glass, Type I. 

 

Dynastat is supplied as a sterile, single unit-of-use vial that is packaged with a 2 ml ampoule with a 

fill volume of 2 ml sodium chloride 9 mg/ml (0.9%) solution (see below for various pack sizes and 

configurations) 

 

Pack sizes 

1 + 1 pack: contains 1 powder vial and 1 solvent ampoule. 

3 + 3 pack: contains 3 powder vials and 3 solvent ampoules. 

5 + 5 pack: contains 5 powder vials and 5 solvent ampoules. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

Dynastat must be reconstituted before use. Dynastat is preservative free. Aseptic technique is 

required for its preparation. 

 

Reconstitution solvents 

Reconstitute Dynastat 40 mg with 2 ml sodium chloride 9 mg/ml (0.9%) solution. 

 

The only other acceptable solvents for reconstitution are: 

• glucose 50 mg/ml (5%) solution for infusion 

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

injection/infusion 

 

Reconstitution process 

Use aseptic technique to reconstitute lyophilised parecoxib (as parecoxib). 

Remove the purple flip-off cap to expose the central portion of the rubber stopper of the 40 mg 

parecoxib vial. Withdraw, with a sterile needle and syringe, 2 ml of an acceptable solvent and insert 

the needle through the central portion of the rubber stopper transferring the solvent into the 40 mg 

vial. Dissolve the powder completely using a gentle swirling motion and inspect the reconstituted 

product before use. The entire contents of the vial should be withdrawn for a single administration. 

 

After reconstitution, the liquid should be a clear solution. Dynastat should be inspected visually for 

particulate matter and discoloration prior to administration. The solution should not be used if 

discolored or cloudy, or if particulate matter is observed. Dynastat should be administered within 

24 hours of reconstitution (see section 6.3), or discarded. 

 



35 

The reconstituted product is isotonic. 

 

IV line solution compatibility 

After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into IV 

lines delivering: 

 

• sodium chloride 9 mg/ml (0.9%) solution for injection/infusion; 

• glucose 50 mg/ml (5%) solution for infusion; 

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

injection/infusion; 

 or 

• Ringer-Lactate solution for injection. 

 

For single use only. Any unused medicinal product or waste material should be disposed of in 

accordance with local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/02/209/006-008 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 22 March 2002 

Date of latest renewal: 24 January 2012 

 

 

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


36 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

 

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 



37 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Pfizer Manufacturing Belgium NV 

Rijksweg 12 

2870 Puurs 

Belgium 

 

 

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. 

 

 

 

 



38 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



39 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



40 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

OUTER CARTON: 40 mg vials 

 

CARTON TEXT - EU/1/02/209/005 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dynastat 40 mg powder for solution for injection 

parecoxib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 40 mg parecoxib, as 42.36 mg parecoxib sodium. After reconstitution with 2 ml 

of solvent, the concentration of parecoxib is 20 mg/ml. Thus, each 2 ml of reconstituted solution 

contains 40 mg of parecoxib. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains disodium hydrogen phosphate, phosphoric acid and sodium hydroxide. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for injection 

 

10 vials 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use.  

For single use only. 

Intravenous or intramuscular use. 

 

 

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 

 

 

 



41 

8. EXPIRY DATE 

 

EXP 

The reconstituted product should be used immediately (up to 24 hours if prepared aseptically), and 

should not be frozen or refrigerated. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions prior to reconstitution. For 

more information on storage see the package leaflet. 

 

 

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 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/02/209/005 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Dynastat 40 mg 

 

 



42 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 



43 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL: 40 mg 

 

TEXT FOR VIAL LABEL - EU/1/02/209/005 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Dynastat 40 mg powder for injection 

parecoxib 

IV/IM 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

 

6. OTHER 

 



44  

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

OUTER CARTON: 40 mg powder and solvent for solution for injection 

 

CARTON TEXT - EU/1/02/209/006 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dynastat 40 mg powder and solvent for solution for injection 

parecoxib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 40 mg parecoxib, as 42.36 mg parecoxib sodium. After reconstitution with 2 ml 

of solvent, the concentration of parecoxib is 20 mg/ml. Thus, each 2 ml of reconstituted solution 

provides 40 mg of parecoxib. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains disodium hydrogen phosphate, phosphoric acid and sodium hydroxide. 

 

2 ml solvent ampoule contains sodium chloride, hydrochloric acid, sodium hydroxide and water for 

injection. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 vial and 1 solvent ampoule 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use.  

For single use only. 

Intravenous or intramuscular use. 

 

 

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. 

 

 



45  

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

The reconstituted product should be used immediately (up to 24 hours if prepared aseptically), and 

should not be frozen or refrigerated. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions prior to reconstitution. For 

more information on storage see the package leaflet. 

 

 

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 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/02/209/006 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

 



46  

16. INFORMATION IN BRAILLE 

 

Dynastat 40 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 



47  

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

OUTER CARTON TEXT: 40 mg powder and solvent for solution for injection 

 

CARTON TEXT - EU/1/02/209/007 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dynastat 40 mg powder and solvent for solution for injection 

parecoxib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 40 mg parecoxib, as 42.36 mg parecoxib sodium. After reconstitution with 2 ml 

of solvent, the concentration of parecoxib is 20 mg/ml. Thus, each 2 ml of reconstituted solution 

provides 40 mg of parecoxib  

 

 

3. LIST OF EXCIPIENTS 

 

Also contains disodium hydrogen phosphate, phosphoric acid and sodium hydroxide.  

 

2 ml solvent ampoule contains sodium chloride, hydrochloric acid, sodium hydroxide and water for 

injection. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

3 vials and 3 solvent ampoules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

For single use only. 

Intravenous or intramuscular use. 

 

 

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. 

 

 



48  

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

The reconstituted product should be used immediately (up to 24 hours if prepared aseptically), and 

should not be frozen or refrigerated. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions prior to reconstitution. For 

more information on storage see the package leaflet. 

 

 

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 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/02/209/007 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

 



49  

16. INFORMATION IN BRAILLE 

 

Dynastat 40 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 



50  

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

OUTER CARTON TEXT: 40 mg powder and solvent for solution for injection 

 

CARTON TEXT - EU/1/02/209/008 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Dynastat 40 mg powder and solvent for solution for injection 

parecoxib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 40 mg parecoxib, as 42.36 mg parecoxib sodium. After reconstitution with 2 ml 

of solvent, the concentration of parecoxib is 20 mg/ml. Thus, each 2 ml of reconstituted solution 

provides 40 mg of parecoxib  

 

 

3. LIST OF EXCIPIENTS 

 

Also contains disodium hydrogen phosphate, phosphoric acid and sodium hydroxide. 

 

2 ml solvent ampoule contains sodium chloride, hydrochloric acid, sodium hydroxide and water for 

injection. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

5 vials and 5 solvent ampoules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

For single use only. 

Intravenous or intramuscular use 

 

 

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. 

 

 



51  

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

The reconstituted product should be used immediately (up to 24 hours if prepared aseptically), and 

should not be frozen or refrigerated.   

 

 

9. SPECIAL STORAGE CONDITIONS 

 

This medicinal product does not require any special storage conditions prior to reconstitution. For 

more information on storage see the package leaflet. 

 

 

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 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/02/209/008 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Dynastat 40 mg 



52  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 

 



53  

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

SOLVENT AMPOULE LABEL : 2 ml 

 

TEXT FOR AMPOULE LABEL - EU/1/02/209/006, EU/1/02/209/007 and EU/1/02/209/008 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Sodium chloride 9 mg/ml (0.9%) solution 

 

 

2. METHOD OF ADMINISTRATION 

 

Solvent for Dynastat 40 mg 

 

Read the package leaflet before use. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

2 ml 

 

 

6. OTHER 

 

 

 



54  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET



55  

Package leaflet: Information for the user 

 

Dynastat 40 mg powder for solution for injection 

parecoxib 

 

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 further questions, ask your doctor or nurse. 

- If you get any side effects, talk to your doctor or nurse. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Dynastat is and what it is used for 

2. What you need to know before you use Dynastat 

3. How to use Dynastat 

4. Possible side effects 

5. How to store Dynastat  

6. Contents of the pack and other information 

 

 

1. What Dynastat is and what it is used for 

 

Dynastat contains the active substance parecoxib. 

 

Dynastat is used for the short-term treatment of pain in adults after an operation. It is one of a 

family of medicines called COX-2 inhibitors (this is short for cyclo-oxygenase-2 inhibitors). Pain 

and swelling are sometimes caused by substances in the body called prostaglandins. Dynastat 

works by lowering the amount of these prostaglandins. 

 

 

2. What you need to know before you use Dynastat 

 

Do not use Dynastat 

- if you are allergic to parecoxib or any of the other ingredients of this medicine (listed in section 

6) 

- if you have had a serious allergic reaction (especially a serious skin reaction) to any medicines 

- if you have had an allergic reaction to a group of medicines called “sulfonamides” (e.g. some 

antibiotics used to treat infections) 

- if you currently have a gastric or intestinal ulcer or bleeding in the stomach or gut 

- if you have had an allergic reaction to acetylsalicylic acid (aspirin) or to other NSAIDs (e.g. 

ibuprofen) or to COX-2 inhibitors. Reactions might include wheezing (bronchospasm), badly 

blocked nose, itchy skin, rash or swelling of the face, lips or tongue, other allergic reactions or 

nasal polyps after taking these medicines 

- if you are more than 6 months pregnant 

- if you are breast-feeding 

- if you have severe liver disease 

- if you have inflammation of the intestines (ulcerative colitis or Crohn’s disease)  

- if you have heart failure  

- if you are about to have heart surgery or surgery on your arteries (including any coronary 

artery procedure) 



56  

- if you have established heart disease and /or cerebrovascular disease e.g. if you have had a heart 

attack, stroke, mini-stroke (TIA) or blockages to blood vessels to the heart or brain or an 

operation to clear or bypass blockages 

- if you have or have had problems with your blood circulation (peripheral arterial disease) 

 

If any of these applies to you, you will not be given the injection.  Tell your doctor or nurse 

immediately. 

 

Warnings and precautions 

 

Do not use Dynastat if you currently have a gastric or intestinal ulcer or gastrointestinal bleeding 

 

Do not use Dynastat if you have severe liver disease 

 

Talk to your doctor or nurse before using Dynastat: 

 

▪ If you have previously had an ulcer, bleeding or perforation of the gastrointestinal tract. 

▪ If you are taking acetylsalicylic acid (aspirin) or other NSAIDs (e.g. ibuprofen) 

▪ If you smoke or drink alcohol 

▪ If you have diabetes 

▪ If you have angina, blood clots, high blood pressure or raised cholesterol 

▪ If you are taking antiplatelet therapies 

▪ If you have fluid retention (oedema) 

▪ If you have liver or kidney disease. 

▪ If you are dehydrated – this may happen if you have had diarrhoea or have been vomiting (being 

sick) or unable to drink fluids 

▪ If you have an infection as it may hide a fever (which is a sign of infection) 

▪ If you use medicines to reduce blood clotting (e.g. warfarin/warfarin like anticoagulants or 

novel oral anti-clotting medicines, e.g. apixaban, dabigatran, and rivaroxaban) 

▪ If you use medicines called corticosteroids (e.g. prednisone) 

▪ If you use a class of medicines used to treat depression called selective serotonin re-uptake 

inhibitors (e.g. sertraline) 

 

Dynastat can lead to an increase in blood pressure or worsening of existing high blood pressure 

which may result in an increase in side effects associated with heart conditions. Your doctor may 

want to monitor your blood pressure during treatment with Dynastat.  

 

Children and adolescents 

Children and adolescents under the age of 18 should not be given Dynastat. 

 

Other medicines and Dynastat 

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. 

Medicines can sometimes interfere with each other. Your doctor may reduce the dose of Dynastat 

or other medicines, or you may need to take a different medicine. It’s especially important to 

mention: 

 

▪ Acetylsalicylic acid (aspirin) or other anti-inflammatory medicines 

▪ Fluconazole – used for fungal infections 

▪ ACE inhibitors, Angiotensin-II inhibitors, beta blockers and diuretics – used for high blood 

pressure and heart conditions 

▪ Ciclosporin or Tacrolimus – used after transplants 

▪ Warfarin – or other warfarin like medicines used to prevent blood clots including newer 

medicines like apixaban, dabigatran, and rivaroxaban 



57  

▪ Lithium – used to treat depression 

▪ Rifampicin – used for bacterial infections 

▪ Antiarrhythmics – used to treat an irregular heartbeat 

▪ Phenytoin or Carbamazepine – used for epilepsy 

▪ Methotrexate – used for rheumatoid arthritis and cancer 

▪ Diazepam – used for sedation and anxiety 

▪ Omeprazole – used for treating ulcers 

 

Pregnancy, breast-feeding and fertility 

▪ If you are pregnant or trying to become pregnant, tell your doctor. Dynastat is not 

recommended in the first 6 months of pregnancy and you must not receive Dynastat in the 

last three months of pregnancy. 

▪ If you are breast-feeding, you must not receive Dynastat, as a small amount of Dynastat 

will be transferred to your breast milk. 

▪ NSAIDs, including Dynastat, may make it more difficult to become pregnant. You should tell 

your doctor if you are planning to become pregnant or if you have problems becoming 

pregnant. 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, 

ask your doctor or nurse for advice before taking this medicine. 

 

Driving and using machines 

If the injection makes you feel dizzy or tired, do not drive or use machines until you feel better 

again. 

 

Dynastat contains 

This medicinal product contains less than 23 mg of sodium in each dose and therefore is essentially 

sodium-free. 

 

 

3. How to use Dynastat 

 

Dynastat will be given to you by a doctor or nurse. They will dissolve the powder before giving you 

the injection, and will inject the solution into a vein or a muscle. The injection may be given rapidly 

and directly into a vein or into an existing intravenous line (a thin tube running into a vein), or it can 

be given slowly and deeply into a muscle. You will only be given Dynastat for short periods, and 

only for pain relief. 

 

The usual dose to start with is 40 mg. 

You may be given another dose – either 20 mg or 40 mg – 6 to 12 hours after the first one. 

 

You will not be given more than 80 mg in 24 hours. 

 

Some people may be given lower doses: 

▪ People with liver problems 

▪ People with severe kidney problems 

▪ Patients over 65 who weigh less than 50 kg 

▪ People taking fluconazole. 

 

If Dynastat is used with strong pain killers (called opioid analgesics) such as morphine the 

dose of Dynastat will be the same as explained above. 

 



58  

If you are given more Dynastat than you should you may experience side effects that have been 

reported with recommended doses. 

 

If you have any further questions on the use of this medicine, ask your doctor or nurse. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Stop taking Dynastat and tell your doctor immediately: 

- if you develop a rash or ulceration in any part of your body (e.g. skin, mouth, eyes, face, lips 
or tongue), or develop any other signs of an allergic reaction such as skin rash, swelling of 

the face, lips or tongue which may cause wheezing, difficulty breathing, or swallowing – this 

occurs rarely 

- if you have blistering or peeling of the skin - this occurs rarely 
- the onset of skin reactions can occur at any time but most often occur in the first month of 

treatment; the reported rate of these events appears to be greater for valdecoxib, a medicine 

related to parecoxib, as compared to other COX-2 inhibitors 

- if you have jaundice (your skin or the whites of your eyes appear yellow) 

- if you have any signs of bleeding in the stomach or intestine, such as passing a black or 

blood-stained bowel movement or vomiting blood 

 

Very common: may affect more than 1 in 10 people 

▪ Nausea (feeling sick) 

 

Common: may affect up to 1 in 10 people 

▪ Change in your blood pressure (up or down) 

▪ You may get back pain 

▪ Ankles, legs and feet may swell (fluid retention) 

▪ You may feel numb – your skin may lose sensitivity to pain and touch 

▪ You may get vomiting, stomach ache, indigestion, constipation, bloating and wind 

▪ Tests may show abnormal kidney function 

▪ You may feel agitated or find it hard to sleep 

▪ Dizziness 

▪ There is a risk of anaemia - changes in red blood cells after an operation that may cause fatigue 

and breathlessness 

▪ You may get a sore throat or difficulty breathing (shortness of breath) 

▪ Your skin may be itchy 

▪ You may pass less urine than usual. 

▪ Dry socket (inflammation and pain after a tooth extraction) 

▪ Increased sweating 

▪ Low levels of potassium in blood test results 

 

Uncommon: may affect up to 1 in 100 people 

▪ Heart attack 
▪ There is a risk of cerebrovascular disease e.g. stroke, or transient ischaemic attack (transient 

reduced blood flow to the brain)/mini-stroke or angina, or blockages to blood vessels to the 

heart or brain  

▪ Blood clot in the lungs 

▪ Worsening of high blood pressure 

▪ Ulcers in the digestive system, chronic stomach acid reflux 

▪ The heart may beat more slowly 



59  

▪ Low blood pressure on standing 

▪ Blood tests may show abnormal liver function 

▪ You may bruise easily due to a low blood platelet count 

▪ Surgical wounds may become infected, abnormal discharge from surgical wounds 

▪ Skin discolouration or bruising 

▪ Complications with skin healing after operations 

▪ High sugar levels in blood tests 

▪ Injection site pain or injection site reaction 

▪ Rash, or raised itchy rash (hives) 

▪ Anorexia (loss of appetite) 

▪ Joint pain 

▪ High levels of blood enzymes in blood tests that indicate injury or stress to the heart, the brain, 

or muscle tissue. 

▪ Dry mouth 

▪ Muscle weakness 

▪ Ear ache 
▪ Unusual abdominal sounds 

 

Rare: may affect up to 1 in 1,000 people 

▪ Rash or ulceration in any part of your body (e.g. skin, mouth, eyes, face, lips or tongue), or 

any other signs of allergic reactions such as skin rash, swelling of the face, lips and tongue, 

wheezing, difficulty breathing or swallowing (potentially fatal) 

▪ Swelling, blistering or peeling of the skin 

▪ Acute kidney failure 

▪ Hepatitis (inflamed liver) 

▪ Inflammation of the gullet (oesophagus) 

▪ Inflammation of the pancreas (can lead to stomach pain) 

 

Not known: frequency cannot be estimated from the available data 

▪ Collapse due to severe low blood pressure 

▪ Heart failure 

▪ Kidney failure 

▪ Racing or irregularity of the heartbeat 

▪ Breathlessness 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. 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 Dynastat 

 

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 carton and on the vial label 

after Exp. The expiry date refers to the last day of that month. 

 

This medicine does not require any special storage conditions prior to reconstitution. 

 

It is recommended that Dynastat is used as soon as possible after it is mixed with solvent, although 

it may be stored if the instructions at the end of the leaflet are strictly followed.  

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


60  

 

The injection solution should be a clear colourless liquid. If there are particles in the injection 

solution or if either the powder or solution is discoloured, the solution will not be used. 

 

 

6. Contents of the pack and other information 

 

What Dynastat contains 

- The active substance is parecoxib (as parecoxib sodium). Each vial contains 40 mg parecoxib, 

as 42.36 mg parecoxib sodium. When reconstituted with 2 ml solvent, provides 20 mg/ml of 

parecoxib. When reconstituted in sodium chloride 9 mg/ml (0.9%) solution, Dynastat contains 

approximately 0.44 mEq of sodium per vial. 

 

- The other ingredients are: 

 

Disodium hydrogen phosphate 

Phosphoric acid and/or sodium hydroxide (for pH adjustment). 

 

What Dynastat looks like and contents of the pack  

Dynastat is available as a white to off-white powder. 

The powder is contained in colourless glass vials (5 ml) with a stopper, sealed with a purple flip-off 

cap on the aluminium overseal. 

 

Marketing Authorisation Holder and Manufacturer 

 

Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, 

Belgium 

Manufacturer: Pfizer Manufacturing Belgium NV, Rijksweg 12, 2870 Puurs, Belgium 

 

For any information about this medicinal product, please contact the local representative of the 

Marketing Authorisation Holder. 

 

België/Belgique/Belgien 

Pfizer S.A./ N.V. 

Tél/Tel: +32 (0)2 554 62 11 

 

Lietuva 

Pfizer Luxembourg SARL filialas Lietuvoje. 

Tel. +3705 2514000 

 

България  

Пфайзер Люксембург САРЛ, Клон България 

Тел.: +359 2 970 4333 

 

Luxembourg/Luxemburg 

Pfizer S.A. 

Tél/Tel: +32 (0)2 554 62 11 

 

Česká Republika 

Pfizer PFE, spol. s r.o. 

Tel: +420 283 004 111 

 

Magyarország 

Pfizer Kft. 

Tel: + 36 1 488 37 00 

 

Danmark 

Pfizer ApS 

Tlf: +45 44 20 11 00 

 

Malta 

Vivian Corporation Ltd. 

Tel: +356 21344610 

 

Deutschland 

Pfizer Pharma GmbH 

Tel: +49 (0)30 550055 51000 

 

Nederland 

Pfizer bv 

Tel: +31 (0)10 406 4301 

 



61  

Eesti 

Pfizer Luxembourg SARL Eesti filiaal 

Tel: +372 666 7500 

 

Norge 

Pfizer Norge AS 

Tlf: +47 67 52 61 00 

 

Ελλάδα 

PFIZER ΕΛΛΑΣ A.E., 

Τλ:  +30 210 67 85 800 

 

Österreich 

Pfizer Corporation Austria Ges.m.b.H. 

Tel: +43 (0)1 521 15-0 

 

España 

Pfizer, S.L. 

Tel: +34 91 490 99 00 

 

Polska 

Pfizer Polska Sp. z o.o., 

Tel.: +48 22 335 61 00 

 

France 

Pfizer 

Tél: +33 (0)1 58 07 34 40 

 

Portugal 

Pfizer Biofarmacêutica, Sociedade Unipessoal Lda 

Tel: +351 21 423 5500 

 

Hrvatska 

Pfizer Croatia d.o.o. 

Tel: + 385 1 3908 777 

 

România 

Pfizer România S.R.L. 

Tel: +40 (0)21 207 28 00 

 

Ireland 

Pfizer Healthcare Ireland 

Tel: 1800 633 363 (toll free) 

+ 44 (0)1304 616161 

 

Slovenija 

Pfizer Luxembourg SARL 

Pfizer, podružnica za svetovanje s področja 

farmacevtske dejavnosti, Ljubljana 

Tel: + 386 (0)152 11 400 

 

Ísland 

Icepharma hf. 

Sími: + 354 540 8000 

 

Slovenská republika 

Pfizer Luxembourg SARL, organizačná zložka 

Tel: +421–2–3355 5500 

 

Italia 

Pfizer S.r.l. 

Tel: +39 06 33 18 21 

 

Suomi/Finland 

Pfizer Oy 

Puh/Tel: +358(0)9 43 00 40 

 

Κύπρος 

PFIZER ΕΛΛΑΣ Α.Ε. (Cyprus Branch)  

Τηλ: +357 22 817690 

 

Sverige  

Pfizer Innovations AB 

Tel: +46 (0)8 550 520 00 

 

Latvija 

Pfizer Luxembourg SARL filiāle Latvijā  

Tel: +371 670 35 775 

 

United Kingdom 

Pfizer Limited 

Tel: +44 (0)1304 616161 

 

 

This leaflet was last revised in <{MM/YYYY}><{month YYYY}>. 

 

<------------------------------------------------------------------------------------------------------------------ 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

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

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


62  

The following information is intended for healthcare professionals only 

 

Dosing. The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), 

followed every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day. The IV 

bolus injection may be given rapidly and directly into a vein or into an existing IV line. The IM 

injection should be given slowly and deeply into the muscle. 

 

There is limited clinical experience with Dynastat treatment beyond three days.  

 

As the cardiovascular risk of cyclooxygenase-2 (COX-2) specific inhibitors may increase with dose 

and duration of exposure, the shortest duration possible and the lowest effective daily dose should 

be used.  

 

Cases of severe hypotension shortly following parecoxib administration have been reported in 

postmarketing experience with parecoxib. Some of these cases have occurred without other signs 

of anaphylaxis. The physician should be prepared to treat severe hypotension. 

 

Administration is by intramuscular (IM) or intravenous (IV) injection . The IM injection is to 

be given slowly and deeply into the muscle and the IV bolus injection may be given rapidly and 

directly into a vein or into an existing IV line. 

 

Administration other than IV or IM 

Modes of administration other than IV or IM (e.g. intra-articular, intrathecal) have not been studied 

and should not be used. 

 

Reconstitution solvents 

This medicinal product must not be mixed with other medicinal products. It is to be 

reconstituted only with one of the following: 

• sodium chloride 9 mg/ml (0.9%) solution for injection/infusion;  

• glucose 50 mg/ml (5%) solution for infusion; or 

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

 injection/infusion. 

 

The following solutions cannot be used for reconstitution: 

• Use of Ringer-Lactate solution for injection or glucose 50 mg/ml (5%) in Ringer-Lactate 

 solution for injection for reconstitution will cause the parecoxib to precipitate from solution 

 and therefore is not recommended. 

• Use of Sterile Water for Injection for reconstitution is not recommended, as the resulting 

 solution is not isotonic. 

 

Reconstitution process 

Use aseptic technique to reconstitute lyophilised parecoxib (as parecoxib sodium).  

40 mg vial: Remove the purple flip-off cap to expose the central portion of the rubber stopper of 

the parecoxib 40 mg vial. Withdraw with a sterile needle and syringe, 2 ml of an acceptable solvent 

and insert the needle through the central portion of the rubber stopper transferring the solvent into 

the parecoxib 40 mg vial. 

 

Dissolve the powder completely using a gentle swirling motion and inspect the reconstituted 

product before use. 

 

The reconstituted solution must not be used if discoloured or cloudy or if particulate matter is 

observed. 

 



63  

The entire contents of the vial should be withdrawn for a single administration.  If a dose 

lower than 40 mg is required, excess medicine should be discarded. 

IV line solution compatibility 

Precipitation may occur when Dynastat is combined in solution with other medicinal products and 

therefore Dynastat must not be mixed with any other drug, either during reconstitution or injection. 

In those patients where the same IV line is to be used to inject another medicinal product, the line 

must be adequately flushed prior to and after Dynastat injection with a solution of known 

compatibility. 

 

After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into 

IV lines delivering the following: 

• sodium chloride 9 mg/ml (0.9%) solution for injection/infusion; 

• glucose 50 mg/ml (5%) solution for infusion;  

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

 injection/infusion; or 

• Ringer-Lactate solution for injection. 

 

It is not recommended to inject into an IV line delivering glucose 50 mg/ml (5%) in Ringer-

Lactate solution for injection, or other IV fluids not listed in this section, as this may cause 

precipitation from solution. 

 

The solution is for single use only and must not be stored in a refrigerator or freezer.  

Chemical and physical in-use stability of the reconstituted solution have been demonstrated for up to 

24 hours at 25C. Thus, 24 hours should be considered the maximum shelf life of the reconstituted 

product. However, due to the importance of microbiological infection risk for injectable products, 

the reconstituted solution should be used immediately unless reconstitution has taken place in 

controlled and validated aseptic conditions. Unless such requirements are met, in-storage times and 

conditions prior to use are the responsibility of the user, and would not normally be longer than 

12 hours at 25C. 



64  

Package leaflet: Information for the user 

 

Dynastat 40 mg powder and solvent for solution for injection 

parecoxib 

 

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 further questions, ask your doctor or nurse. 

- If you get any side effects, talk to your doctor or nurse. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Dynastat is and what it is used for 

2. What you need to know before you use Dynastat 

3. How to use Dynastat 

4. Possible side effects 

5. How to store Dynastat  

6. Contents of the pack and other information 

 

 

1. What Dynastat is and what it is used for 

 

Dynastat contains the active substance parecoxib. 

 

Dynastat is used for the short-term treatment of pain in adults after an operation. It is one of a 

family of medicines called COX-2 inhibitors (this is short for cyclo-oxygenase-2 inhibitors). Pain 

and swelling are sometimes caused by substances in the body called prostaglandins. Dynastat 

works by lowering the amount of these prostaglandins. 

 

 

2. What you need to know before you use Dynastat  

 

Do not take Dynastat 

- if you are allergic to parecoxib or any of the other ingredients of this medicine (listed in section 

6) 

- if you have had a serious allergic reaction (especially a serious skin reaction) to any medicines  

- if you have had an allergic reaction to a group of medicines called “sulfonamides” (e.g. some 

antibiotics used to treat infections) 

- if you currently have a gastric or intestinal ulcer or bleeding in the stomach or gut 

- if you have had an allergic reaction to acetylsalicylic acid (aspirin) or to other NSAIDs (e.g. 

ibuprofen) or to COX-2 inhibitors. Reactions might include wheezing (bronchospasm), badly 

blocked nose, itchy skin, rash or swelling of the face, lips or tongue, other allergic reactions or 

nasal polyps after taking these medicines 

- if you are more than 6 months pregnant 

- if you are breast-feeding 

- if you have severe liver disease 

- if you have inflammation of the intestines (ulcerative colitis or Crohn’s disease)  

- if you have heart failure  

- if you are about to have heart surgery or surgery on your arteries (including any coronary 

artery procedure)  



65  

- if you have established heart disease and /or cerebrovascular disease e.g. if you have had a heart 

attack, stroke, mini-stroke (TIA) or blockages to blood vessels to the heart or brain or an 

operation to clear or bypass blockages 

- if you have or have had problems with your blood circulation (peripheral arterial disease) 

 

If any of these applies to you, you will not be given the injection.  Tell your doctor or nurse 

immediately. 

 

Warnings and precautions 

 

Do not use Dynastat if you currently have a gastric or intestinal ulcer or gastrointestinal bleeding 

 

Do not use Dynastat if you have severe liver disease 

 

Talk to your doctor or nurse before using Dynastat: 

 

▪ If you have previously had an ulcer, bleeding or perforation of the gastrointestinal tract 

▪ If you are taking acetylsalicylic acid (aspirin) or other NSAIDs (e.g. ibuprofen) 

▪ If you smoke or drink alcohol 

▪ If you have diabetes 

▪ If you have angina, blood clots, high blood pressure or raised cholesterol 

▪ If you are taking antiplatelet therapies 

▪ If you have fluid retention (oedema) 

▪ If you have liver or kidney disease. 

▪ If you are dehydrated – this may happen if you have had diarrhoea or have been vomiting (being 

sick) or unable to drink fluids 

▪ If you have an infection as it may hide a fever (which is a sign of infection) 

▪ If you use medicines to reduce blood clotting (e.g. warfarin/warfarin like anticoagulants or 

novel oral anti-clotting medicines, e.g. apixaban, dabigatran, and rivaroxaban) 

▪ If you use medicines called corticosteroids (e.g. prednisone) 

▪ If you use a class of medicines used to treat depression called selective serotonin re-uptake 

inhibitors (e.g. sertraline) 

 

Dynastat can lead to an increase in blood pressure or worsening of existing high blood pressure 

which may result in an increase in side effects associated with heart conditions. Your doctor may 

want to monitor your blood pressure during treatment with Dynastat.  

 

Children and adolescents  

Children and adolescents under the age of 18 should not be given Dynastat. 

 

Other medicines and Dynastat 

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. 

Medicines can sometimes interfere with each other. Your doctor may reduce the dose of Dynastat 

or other medicines, or you may need to take a different medicine. It’s especially important to 

mention: 

 

▪ Acetylsalicylic acid (aspirin) or other anti-inflammatory medicines 

▪ Fluconazole – used for fungal infections 

▪ ACE inhibitors, Angiotensin-II inhibitors, beta blockers and diuretics – used for high blood 

pressure and heart conditions 

▪ Ciclosporin or Tacrolimus – used after transplants 

▪ Warfarin – or other warfarin like medicines used to prevent blood clots including newer 

medicines like apixaban, dabigatran, and rivaroxaban 



66  

▪ Lithium – used to treat depression 

▪ Rifampicin – used for bacterial infections 

▪ Antiarrhythmics – used to treat an irregular heartbeat 

▪ Phenytoin or Carbamazepine – used for epilepsy 

▪ Methotrexate – used for rheumatoid arthritis and cancer 

▪ Diazepam – used for sedation and anxiety 

▪ Omeprazole – used for treating ulcers 

 

Pregnancy, breast-feeding and fertility 

▪ If you are pregnant or trying to become pregnant, tell your doctor. Dynastat is not 

recommended in the first 6 months of pregnancy and you must not receive Dynastat in the 

last three months of pregnancy. 

▪ If you are breast-feeding, you must not receive Dynastat, as a small amount of Dynastat 

will be transferred to your breast milk. 

▪ NSAIDs, including Dynastat, may make it more difficult to become pregnant. You should tell 

your doctor if you are planning to become pregnant or if you have problems becoming 

pregnant. 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, 

ask your doctor or nurse for advice before taking this medicine. 

 

Driving and using machines 

If the injection makes you feel dizzy or tired, do not drive or use machines until you feel better 

again. 

 

Dynastat contains 

This medicinal product contains less than 23 mg of sodium in each dose and therefore is essentially 

sodium-free. 

 

 

3. How to use Dynastat 

 

Dynastat will be given to you by a doctor or nurse. They will dissolve the powder before giving you 

the injection, and will inject the solution into a vein or a muscle. The injection may be given rapidly 

and directly into a vein or into an existing intravenous line (a thin tube running into a vein), or it can 

be given slowly and deeply into a muscle. You will only be given Dynastat for short periods, and 

only for pain relief. 

 

The usual dose to start with is 40 mg. 

You may be given another dose – either 20 mg or 40 mg – 6 to 12 hours after the first one.  

 

You will not be given more than 80 mg in 24 hours. 

 

Some people may be given lower doses:  

▪ People with liver problems 

▪ People with severe kidney problems 

▪ Patients over 65 who weigh less than 50 kg 

▪ People taking fluconazole. 

 

If Dynastat is used with strong pain killers (called opioid analgesics) such as morphine the 

dose of Dynastat will be the same as explained above. 

 



67  

If you are given more Dynastat than you should you may experience side effects that have been 

reported with recommended doses. 

 

If you have any further questions on the use of this medicine, ask your doctor or nurse. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Stop taking Dynastat and tell your doctor immediately: 

- if you develop a rash or ulceration in any part of your body (e.g. skin, mouth, eyes, face, lips or 
tongue), or develop any other signs of an allergic reaction such as skin rash, swelling of  the 

face, lips or tongue which may cause wheezing, difficulty breathing, or swallowing – this 

occurs rarely 

- if you have blistering or peeling of the skin – this occurs rarely 
- the onset of skin reactions can occur at any time but most often occur in the first month of 

treatment; the reported rate of these events appears to be greater for valdecoxib, a medicine 

related to parecoxib, as compared to other COX-2 inhibitors 

- if you have jaundice (your skin or the whites of your eyes appear yellow) 

- if you have any signs of bleeding in the stomach or intestine, such as passing a black or 

blood-stained bowel movement or vomiting blood 

 

Very common: may affect more than 1 in 10 people 

▪ Nausea (feeling sick) 

 

Common: may affect up to 1 in 10 people 

▪ Change in your blood pressure (up or down) 

▪ You may get back pain 

▪ Ankles, legs and feet may swell (fluid retention) 

▪ You may feel numb – your skin may lose sensitivity to pain and touch 

▪ You may get vomiting, stomach ache, indigestion, constipation, bloating and wind 

▪ Tests may show abnormal kidney function 

▪ You may feel agitated or find it hard to sleep 

▪ Dizziness 

▪ There is a risk of anaemia - changes in red blood cells after an operation that may cause fatigue 

and breathlessness 

▪ You may get a sore throat or difficulty breathing (shortness of breath) 

▪ Your skin may be itchy 

▪ You may pass less urine than usual. 

▪ Dry socket (inflammation and pain after a tooth extraction) 

▪ Increased sweating 

▪ Low levels of potassium in blood test results 

 

Uncommon: may affect up to 1 in 100 people 

▪ Heart attack 
▪ There is a risk of cerebrovascular disease e.g. stroke, or transient ischaemic attack (transient 

reduced blood flow to the brain)/mini-stroke or angina, or blockages to blood vessels to the 

heart or brain  

▪ Blood clot in the lungs 

▪ Worsening of high blood pressure 

▪ Ulcers in the digestive system, chronic stomach acid reflux 

▪ The heart may beat more slowly 

▪ Low blood pressure on standing 



68  

▪ Blood tests may show abnormal liver function  

▪ You may bruise easily due to a low blood platelet count 

▪ Surgical wounds may become infected, abnormal discharge from surgical wounds 

▪ Skin discolouration or bruising 

▪ Complications with skin healing after operations 

▪ High sugar levels in blood tests 

▪ Injection site pain or injection site reaction 

▪ Rash, or raised itchy rash (hives) 

▪ Anorexia (loss of appetite) 

▪ Joint pain 

▪ High levels of blood enzymes in blood tests that indicate injury or stress to the heart, the brain, 

or muscle tissue. 

▪ Dry mouth 

▪ Muscle weakness 

▪ Ear ache 
▪ Unusual abdominal sounds  

 

Rare: may affect up to 1 in 1,000 people 

▪ Rash or ulceration in any part of your body (e.g. skin, mouth, eyes, face, lips or tongue), or 

any other signs of allergic reactions such as skin rash, swelling of the face, lips and tongue, 

wheezing, difficulty breathing or swallowing (potentially fatal) 

▪ Swelling, blistering or peeling of the skin  

▪ Acute kidney failure 

▪ Hepatitis (inflamed liver) 

▪ Inflammation of the gullet (oesophagus) 

▪ Inflammation of the pancreas (can lead to stomach pain) 

 

Not known: frequency cannot be estimated from the available data 

▪ Collapse due to severe low blood pressure 

▪ Heart failure 

▪ Kidney failure 

▪ Racing or irregularity of the heartbeat 

▪ Breathlessness 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. 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 Dynastat 

 

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 carton and on the vial label 

after Exp. The expiry date refers to the last day of that month. 

 

This medicine does not require any special storage conditions prior to reconstitution. 

 

It is recommended that Dynastat is used as soon as possible after it is mixed with solvent, although 

it may be stored if the instructions at the end of the leaflet are strictly followed.  

 

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


69  

The injection solution should be a clear colourless liquid. If there are particles in the injection 

solution or if either the powder or solution is discoloured, the solution will not be used. 

 

 

6. Contents of the pack and other information 

 

What Dynastat contains  

- The active substance is parecoxib (as parecoxib sodium). Each vial contains 40 mg parecoxib, 

as 42.36 mg parecoxib sodium. When reconstituted with 2 ml solvent, provides 20 mg/ml of 

parecoxib. When reconstituted in sodium chloride 9 mg/ml (0.9%) solution, Dynastat contains 

approximately 0.44 mEq of sodium per vial. 

 

- The other ingredients are: 

Powder 

Disodium hydrogen phosphate 

Phosphoric acid and/or sodium hydroxide (for pH adjustment). 

 

Solvent 

Sodium chloride 

Hydrochloric acid or sodium hydroxide (for pH adjustment) 

Water for injection. 

 

What Dynastat looks like and contents of the pack  

Dynastat is available as a white to off-white powder. 

The powder is contained in colourless glass vials (5 ml) with a stopper, sealed with a purple flip-off 

cap on the aluminium overseal. 

The solvent is contained in colourless neutral glass ampoules (2 ml). 

 

Marketing Authorisation Holder and Manufacturer 

 

Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, 

Belgium 

Manufacturer: Pfizer Manufacturing Belgium NV, Rijksweg 12, 2870 Puurs, Belgium 

 

For any information about this medicinal product, please contact the local representative of  the 

Marketing Authorisation Holder. 

  

België/Belgique/Belgien 

Pfizer S.A./ N.V. 

Tél/Tel: +32 (0)2 554 62 11 

 

Lietuva 

Pfizer Luxembourg SARL filialas Lietuvoje. 

Tel. +3705 2514000 

 

България  

Пфайзер Люксембург САРЛ, Клон България  

Тел.: +359 2 970 4333 

 

Luxembourg/Luxemburg 

Pfizer S.A. 

Tél/Tel: +32 (0)2 554 62 11 

 

Česká Republika 

Pfizer PFE, spol. s r.o.  

Tel: +420 283 004 111 

 

Magyarország 

Pfizer Kft.  

Tel.: + 36 1 488 37 00  

 

Danmark 

Pfizer ApS 

Tlf: +45 44 20 11 00 

 

Malta 

Vivian Corporation Ltd. 

Tel: +356 21344610 

 



70  

Deutschland 

Pfizer Pharma GmbH 

Tel:+ 49 (0)30 550055 51000 

 

Nederland 

Pfizer bv 

Tel: +31 (0)10 406 4301 

 

Eesti 

Pfizer Luxembourg SARL Eesti filiaal 

Tel: +372 666 7500 

 

Norge 

Pfizer Norge AS 

Tlf: +47 67 52 61 00 

 

Ελλάδα 

PFIZER ΕΛΛΑΣ A.E., 

Τλ:  +30 210 67 85 800 

 

Österreich 

Pfizer Corporation Austria Ges.m.b.H. 

Tel: +43 (0)1 521 15-0 

 

España 

Pfizer, S.L. 

Tel: +34 91 490 99 00 

 

Polska 

Pfizer Polska Sp. z o.o.,  

Tel.: +48 22 335 61 00 

 

France 

Pfizer 

Tél: +33 (0)1 58 07 34 40 

Portugal 

Pfizer Biofarmacêutica, Sociedade Unipessoal Lda 

Tel: +351 21 423 5500 

Hrvatska 

Pfizer Croatia d.o.o. 

Tel: + 385 1 3908 777 

 

România 

Pfizer România S.R.L. 

Tel: +40 (0)21 207 28 00 

 

Ireland 

Pfizer Healthcare Ireland 

Tel: 1800 633 363 (toll free) 

+44 (0)1304 616161 

 

Slovenija 

Pfizer Luxembourg SARL 

Pfizer, podružnica za svetovanje s področja 

farmacevtske dejavnosti, Ljubljana 

Tel: + 386 (0)152 11 400 

 

Ísland 

Icepharma hf. 

Sími: + 354 540 8000 

 

Slovenská republika 

Pfizer Luxembourg SARL, organizačná zložka 

Tel: +421–2–3355 5500 

 

Italia 

Pfizer S.r.l. 

Tel: +39 06 33 18 21 

 

Suomi/Finland 

Pfizer Oy 

Puh/Tel: +358(0)9 43 00 40 

 

Κύπρος 

PFIZER ΕΛΛΑΣ Α.Ε. (Cyprus Branch)   

Τηλ: +357 22 817690 

 

Sverige  

Pfizer Innovations AB 

Tel: +46 (0)8 550 520 00 

 

Latvija 

Pfizer Luxembourg SARL filiāle Latvijā  

Tel: +371 670 35 775 

 

United Kingdom 

Pfizer Limited 

Tel: +44 (0)1304 616161 

 

 

This leaflet was last revised in <{MM/YYYY}><{month YYYY}>. 

<---------------------------------------------------------------------------------------------------------------

--- 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

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

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


71  

The following information is intended for healthcare professionals only 

 

Dosing. The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), 

followed every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day. The IV 

bolus injection may be given rapidly and directly into a vein or into an existing IV line. The IM 

injection should be given slowly and deeply into the muscle. 

 

There is limited clinical experience with Dynastat treatment beyond three days.  

 

As the cardiovascular risk of cyclooxygenase-2 (COX-2) specific inhibitors may increase with dose 

and duration of exposure, the shortest duration possible and the lowest effective daily dose should 

be used.  

 

Cases of severe hypotension shortly following parecoxib administration have been reported in 

postmarketing experience with parecoxib. Some of these cases have occurred without other signs 

of anaphylaxis. The physician should be prepared to treat severe hypotension. 

 

Administration is by intramuscular (IM) or intravenous (IV) injection . The IM injection is to 

be given slowly and deeply into the muscle and the IV bolus injection may be given rapidly and 

directly into a vein or into an existing IV line.  

 

Administration other than IV or IM 

Modes of administration other than IV or IM (e.g. intra-articular, intrathecal) have not been studied 

and should not be used.  

 

Reconstitution solvents 

This medicinal product must not be mixed with other medicinal products. It is to be 

reconstituted only with one of the following: 

• sodium chloride 9 mg/ml (0.9%) solution for injection/infusion;  

• glucose 50 mg/ml (5%) solution for infusion; or 

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

 injection/infusion. 

 

The following solutions cannot be used for reconstitution: 

• Use of Ringer-Lactate solution for injection or glucose 50 mg/ml (5%) in Ringer-Lactate 

 solution for injection for reconstitution will cause the parecoxib to precipitate from solution 

 and therefore is not recommended. 

• Use of Sterile Water for Injection for reconstitution is not recommended, as the resulting 

 solution is not isotonic. 

 

Reconstitution process 

Use aseptic technique to reconstitute lyophilised parecoxib (as parecoxib sodium).  

40 mg vial: Remove the purple flip-off cap to expose the central portion of the rubber stopper of 

the parecoxib 40 mg vial. Withdraw with a sterile needle and syringe, 2 ml of an acceptable solvent 

and insert the needle through the central portion of the rubber stopper transferring the solvent into 

the parecoxib 40 mg vial. 

 

Dissolve the powder completely using a gentle swirling motion and inspect the reconstituted 

product before use. 

 

The reconstituted solution must not be used if discoloured or cloudy or if particulate matter is 

observed. 

 



72  

The entire contents of the vial should be withdrawn for a single administration.  If a dose 

lower than 40 mg is required, excess medicine should be discarded. 

IV line solution compatibility 

Precipitation may occur when Dynastat is combined in solution with other medicinal products and 

therefore Dynastat must not be mixed with any other drug, either during reconstitution or injection. 

In those patients where the same IV line is to be used to inject another medicinal product, the line 

must be adequately flushed prior to and after Dynastat injection with a solution of known 

compatibility. 

 

After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into 

IV lines delivering the following: 

• sodium chloride 9 mg/ml (0.9%) solution for injection/infusion; 

• glucose 50 mg/ml (5%) solution for infusion; 

• sodium chloride 4.5 mg/ml (0.45%) and glucose 50 mg/ml (5%) solution for 

 injection/infusion; or  

• Ringer-Lactate solution for injection. 

 

It is not recommended to inject into an IV line delivering glucose 50 mg/ml (5%) in Ringer-

Lactate solution for injection, or other IV fluids not listed in this section, as this may cause 

precipitation from solution. 

 

The solution is for single use only and must not be stored in a refrigerator or freezer.  

Chemical and physical in-use stability of the reconstituted solution have been demonstrated for up to 

24 hours at 25C. Thus, 24 hours should be considered the maximum shelf life of the reconstituted 

product. However, due to the importance of microbiological infection risk for injectable products, 

the reconstituted solution should be used immediately unless reconstitution has taken place in 

controlled and validated aseptic conditions. Unless such requirements are met, in-storage times and 

conditions prior to use are the responsibility of the user, and would not normally be longer than 

12 hours at 25C. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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