Invanz

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

 



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1. NAME OF THE MEDICINAL PRODUCT

INVANZ 1 g powder for concentrate for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 1.0 g ertapenem.

Excipient with known effect
Each 1.0 g dose contains approximately 6.0 mEq of sodium (approximately 137 mg).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for concentrate for solution for infusion. 
White to off-white powder.

4. CLINICAL PARTICULARS 

4.1 Therapeutic indications

Treatment

INVANZ is indicated in paediatric patients (3 months to 17 years of age) and in adults for the
treatment of the following infections when caused by bacteria known or very likely to be susceptible 
to ertapenem and when parenteral therapy is required (see sections 4.4 and 5.1):

 Intra-abdominal infections
 Community acquired pneumonia
 Acute gynaecological infections
 Diabetic foot infections of the skin and soft tissue (see section 4.4)

Prevention

INVANZ is indicated in adults for the prophylaxis of surgical site infection following elective 
colorectal surgery (see section 4.4).

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Posology

Treatment
Adults and adolescents (13 to 17 years of age): The dose of INVANZ is 1 gram (g) given once a day 
by the intravenous route (see section 6.6).

Infants and children (3 months to 12 years of age): The dose of INVANZ is 15 mg/kg given twice 
daily (not to exceed 1 g/day) by the intravenous route (see section 6.6).

 



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Prevention
Adults: To prevent surgical site infections following elective colorectal surgery, the recommended 
dosage is 1 g administered as a single intravenous dose to be completed within 1 hour prior to the 
surgical incision.

Paediatric population
The safety and efficacy of INVANZ in children below 3 months of age have not yet been established. 
No data are available.

Renal impairment
INVANZ may be used for the treatment of infections in adult patients with mild to moderate renal 
impairment. In patients whose creatinine clearance is  30 mL/min/1.73 m2, no dosage adjustment is 
necessary. There are inadequate data on the safety and efficacy of ertapenem in patients with severe 
renal impairment to support a dose recommendation. Therefore, ertapenem should not be used in these 
patients (see section 5.2.). There are no data in children and adolescents with renal impairment.

Haemodialysis
There are inadequate data on the safety and efficacy of ertapenem in patients on haemodialysis to 
support a dose recommendation. Therefore, ertapenem should not be used in these patients.

Hepatic impairment
No dosage adjustment is recommended in patients with impaired hepatic function (see section 5.2).

Elderly
The recommended dose of INVANZ should be administered, except in cases of severe renal 
impairment (see Renal impairment).

Method of administration

Intravenous administration: INVANZ should be infused over a period of 30 minutes.

The usual duration of therapy with INVANZ is 3 to 14 days but may vary depending on the type and 
severity of infection and causative pathogen(s). When clinically indicated, a switch to an appropriate 
oral antibacterial agent may be implemented if clinical improvement has been observed.

For instructions on preparation of the medicinal product before administration, see section 6.6.

4.3 Contraindications

 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
 Hypersensitivity to any other carbapenem antibacterial agent
 Severe hypersensitivity (e.g., anaphylactic reaction, severe skin reaction) to any other type of 

beta-lactam antibacterial agent (e.g., penicillins or cephalosporins).

4.4 Special warnings and precautions for use

Hypersensitivity
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients 
receiving therapy with beta-lactams. These reactions are more likely to occur in individuals with a 
history of sensitivity to multiple allergens. Before initiating therapy with ertapenem, careful inquiry 
should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other 
beta-lactams and other allergens (see section 4.3). If an allergic reaction to ertapenem occurs (see 
section 4.8), discontinue the therapy immediately. Serious anaphylactic reactions require 
immediate emergency treatment.

 



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Superinfection
Prolonged use of ertapenem may result in overgrowth of non-susceptible organisms. Repeated 
evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate 
measures should be taken.

Antibiotic-associated colitis
Antibiotic-associated colitis and pseudomembranous colitis have been reported with ertapenem and 
may range in severity from mild to life-threatening. Therefore, it is important to consider this 
diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial 
agents. Discontinuation of therapy with INVANZ and the administration of specific treatment for 
Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be 
given.

Seizures
Seizures have been reported during clinical investigation in adult patients treated with ertapenem (1 g 
once a day) during therapy or in the 14-day follow-up period. Seizures occurred most commonly in 
elderly patients and those with pre-existing central nervous system (CNS) disorders (e.g. brain lesions 
or history of seizures) and/or compromised renal function. Similar observations have been made in the 
post-marketing environment.

Concomitant use with valproic acid 
The concomitant use of ertapenem and valproic acid/sodium valproate is not recommended (see 
section 4.5).

Sub-optimal exposure
Based on the data available it cannot be excluded that in the few cases of surgical interventions 
exceeding 4 hours, patients could be exposed to sub-optimal ertapenem concentrations and 
consequently to a risk of potential treatment failure. Therefore, caution should be exercised in such 
unusual cases.

Excipient
This medicinal product contains approximately 6.0 mEq (approximately 137 mg) of sodium per 1.0 g 
dose which should be taken into consideration by patients on a controlled sodium diet.

Considerations for use in particular populations
Experience in the use of ertapenem in the treatment of severe infections is limited. In clinical studies 
for the treatment of community-acquired pneumonia, in adults, 25 % of evaluable patients treated with 
ertapenem had severe disease (defined as pneumonia severity index > III). In a clinical study for the 
treatment of acute gynaecologic infections, in adults, 26 % of evaluable patients treated with 
ertapenem had severe disease (defined as temperature ≥ 39C and/or bacteraemia); ten patients had 
bacteraemia. Of evaluable patients treated with ertapenem in a clinical study for the treatment of 
intra-abdominal infections, in adults, 30 % had generalised peritonitis and 39 % had infections 
involving sites other than the appendix including the stomach, duodenum, small bowel, colon, and 
gallbladder; there were limited numbers of evaluable patients who were enrolled with APACHE II 
scores ≥ 15 and efficacy in these patients has not been established.

The efficacy of INVANZ in the treatment of community acquired pneumonia due to penicillin-
resistant Streptococcus pneumoniae has not been established. 

Efficacy of ertapenem in the treatment of diabetic foot infections with concurrent osteomyelitis has not 
been established.

There is relatively little experience with ertapenem in children less than two years of age. In this age 
group, particular care should be taken to establish the susceptibility of the infecting organism(s) to 
ertapenem. No data are available in children under 3 months of age.

 



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4.5 Interaction with other medicinal products and other forms of interaction

Interactions caused by inhibition of P-glycoprotein-mediated clearance or CYP-mediated clearance of 
medicinal products are unlikely (see section 5.2).

Decreases in valproic acid levels that may fall below the therapeutic range have been reported when 
valproic acid was co-administered with carbapenem agents. The lowered valproic acid levels can lead 
to inadequate seizure control; therefore, concomitant use of ertapenem and valproic acid/sodium 
valproate is not recommended and alternative antibacterial or anti-convulsant therapies should be 
considered.

4.6 Fertility, pregnancy and lactation

Pregnancy
Adequate and well-controlled studies have not been performed in pregnant women. Animal studies do 
not indicate direct or indirect harmful effects with respect to pregnancy, embryo-foetal development, 
parturition or post-natal development. However, ertapenem should not be used during pregnancy 
unless the potential benefit outweighs the possible risk to the foetus.

Breast-feeding
Ertapenem is excreted in human milk. Because of the potential for adverse reactions on the infant, 
mothers should not breast-feed their infants while receiving ertapenem.

Fertility
There are no adequate and well-controlled studies regarding the effect of ertapenem use on fertility in 
men and women. Preclinical studies do not indicate direct or indirect harmful effects with respect to 
fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

INVANZ may influence patients' ability to drive and use machines. Patients should be informed that 
dizziness and somnolence have been reported with INVANZ (see section 4.8).

4.8 Undesirable effects

Summary of the safety profile
Adults
The total number of patients treated with ertapenem in clinical studies was over 2,200 of which over 
2,150 received a 1 g dose of ertapenem. Adverse reactions (i.e., considered by the investigator to be 
possibly, probably, or definitely related to the medicinal product) were reported in approximately 
20 % of patients treated with ertapenem. Treatment was discontinued due to adverse reactions in 1.3 % 
of patients. An additional 476 patients received ertapenem as a single 1 g dose prior to surgery in a 
clinical study for the prophylaxis of surgical site infections following colorectal surgery.

For patients who received only INVANZ, the most common adverse reactions reported during therapy 
plus follow-up for 14 days after treatment was stopped were: diarrhoea (4.8 %), infused vein 
complication (4.5 %) and nausea (2.8 %).

For patients who received only INVANZ, the most frequently reported laboratory abnormalities and 
their respective incidence rates during therapy plus follow-up for 14 days after treatment was stopped 
were: elevations in ALT (4.6 %), AST (4.6 %), alkaline phosphatase (3.8 %) and platelet count 
(3.0 %). 

 



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Paediatric population (3 months to 17 years of age):
The total number of patients treated with ertapenem in clinical studies was 384. The overall safety 
profile is comparable to that in adult patients. Adverse reactions (i.e., considered by the investigator to 
be possibly, probably, or definitely related to the medicinal product) were reported in approximately 
20.8 % of patients treated with ertapenem. Treatment was discontinued due to adverse reactions in 
0.5 % of patients.

For patients who received only INVANZ, the most common adverse reactions reported during therapy 
plus follow-up for 14 days after treatment was stopped were: diarrhoea (5.2 %) and infusion site pain 
(6.1 %).

For patients who received only INVANZ, the most frequently reported laboratory abnormalities and 
their respective incidence rates during therapy plus follow-up for 14 days after treatment was stopped 
were: decreases in neutrophil count (3.0 %), and elevations in ALT (2.9 %) and AST (2.8 %).

Tabulated list of adverse reactions
For patients who received only INVANZ, the following adverse reactions were reported during 
therapy plus follow-up for 14 days after treatment was stopped:

Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); 
Very rare (< 1/10,000); Not known (cannot be estimated from the available data)

Adults 18 years of age and older Children and adolescents 
(3 months to 17 years of age)

Infections and infestations Uncommon: Oral candidiasis, 
candidiasis, fungal infection, 
pseudomembranous enterocolitis,
vaginitis
Rare: Pneumonia, 
dermatomycosis, postoperative 
wound infection, urinary tract 
infection

Blood and lymphatic system 
disorders

Rare: Neutropenia, 
thrombocytopenia

Immune system disorders Rare: Allergy
Not known: Anaphylaxis 
including anaphylactoid reactions

Metabolism and nutrition 
disorders

Uncommon: Anorexia
Rare: Hypoglycaemia

Psychiatric disorders Uncommon: Insomnia, confusion
Rare: Agitation, anxiety, 
depression
Not known: Altered mental status 
(including aggression, delirium, 
disorientation, mental status 
changes)

Not known: Altered mental 
status (including aggression)

Nervous system disorders Common: Headache
Uncommon: Dizziness, 
somnolence, taste perversion, 
seizure (see section 4.4)
Rare: Tremor, syncope
Not known: Hallucinations, 
depressed level of consciousness, 
dyskinesia, myoclonus, gait 
disturbance

Uncommon: Headache
Not known: Hallucinations

Eye disorders Rare: Scleral disorder

 



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Adults 18 years of age and older Children and adolescents 
(3 months to 17 years of age)

Cardiac disorders Uncommon: Sinus bradycardia
Rare: Arrhythmia, tachycardia

Vascular disorders Common: Infused vein 
complication, 
phlebitis/thrombophlebitis
Uncommon: Hypotension
Rare: Haemorrhage, increased 
blood pressure

Uncommon: Hot flush, 
hypertension

Respiratory, thoracic and 
mediastinal disorders

Uncommon: Dyspnoea, 
pharyngeal discomfort
Rare: Nasal congestion, cough, 
epistaxis, rales/rhonchi, wheezing

Gastrointestinal disorders Common: Diarrhoea, nausea, 
vomiting
Uncommon: Constipation, acid 
regurgitation, dry mouth, 
dyspepsia, abdominal pain
Rare: Dysphagia, faecal 
incontinence, pelvic peritonitis
Not known: teeth staining

Common: Diarrhoea
Uncommon: Faeces 
discoloured, melaena

Hepato-biliary disorders Rare: Cholecystitis, jaundice, liver 
disorder

Skin and subcutaneous tissue 
disorders

Common: Rash, pruritus
Uncommon: Erythema, urticaria
Rare: Dermatitis, desquamation 
Not known: Acute Generalised 
Exanthematous Pustulosis
(AGEP), Drug Rash with 
Eosinophilia and Systemic 
Symptoms (DRESS syndrome)

Common: Diaper dermatitis
Uncommon: Erythema, rash, 
petechiae

Musculoskeletal and 
connective tissue disorders

Rare: Muscle cramp, shoulder 
pain
Not known: Muscular weakness

Renal and urinary disorders Rare: Renal insufficiency, acute 
renal insufficiency

Pregnancy, puerperium and 
perinatal conditions

Rare: Abortion

Reproductive system and 
breast disorders

Rare: Genital bleeding

General disorders and 
administration site conditions

Uncommon: Extravasation, 
asthenia/fatigue, fever, 
oedema/swelling, chest pain
Rare: Injection-site induration, 
malaise

Common: Infusion site pain
Uncommon: Infusion site 
burning, infusion site pruritus, 
infusion site erythema, 
injection site erythema, 
infusion site warmth

 



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Adults 18 years of age and older Children and adolescents 
(3 months to 17 years of age)

Investigations
Chemistry Common: Elevations in ALT, 

AST, alkaline phosphatase
Uncommon: Increases in total 
serum bilirubin, direct serum 
bilirubin, indirect serum bilirubin, 
serum creatinine, serum urea, 
serum glucose
Rare: Decreases in serum 
bicarbonate, serum creatinine, and 
serum potassium; increases in 
serum LDH, serum phosphorus, 
serum potassium

Common: Elevations in ALT 
and AST

Haematology Common: Elevation in platelet 
count
Uncommon: Decreases in white 
blood cells, platelet count, 
segmented neutrophils, 
haemoglobin and haematocrit; 
increases in eosinophils, activated 
partial thromboplastin time, 
prothrombin time, segmented 
neutrophils, and white blood cells
Rare: Decrease in lymphocytes; 
increases in band neutrophils, 
lymphocytes, metamyelocytes, 
monocytes, myelocytes; atypical 
lymphocytes

Common: Decreases in 
neutrophil count
Uncommon: Increases in 
platelet count, activated 
partial thromboplastin time, 
prothrombin time, decreases 
in haemoglobin

Urinalysis Uncommon: Increases in urine 
bacteria, urine white blood cells, 
urine epithelial cells, and urine red 
blood cells; urine yeast present
Rare: Increase in urobilinogen

Miscellaneous Uncommon: Positive Clostridium 
difficile toxin

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

No specific information is available on the treatment of overdose with ertapenem. Overdosing of 
ertapenem is unlikely. Intravenous administration of ertapenem at a 3 g daily dose for 8 days to 
healthy adult volunteers did not result in significant toxicity. In clinical studies in adults inadvertent 
administration of up to 3 g in a day did not result in clinically important adverse reactions. In 
paediatric clinical studies, a single intravenous (IV) dose of 40 mg/kg up to a maximum of 2 g did not 
result in toxicity.

However, in the event of an overdose, treatment with INVANZ should be discontinued and general 
supportive treatment given until renal elimination takes place.

 

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Ertapenem can be removed to some extent by haemodialysis (see section 5.2); however, no 
information is available on the use of haemodialysis to treat overdose.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

General properties

Pharmacotherapeutic group: Antibacterials for systemic use, carbapenems, ATC code: J01DH03

Mechanism of action
Ertapenem inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins 
(PBPs). In Escherichia coli, affinity is strongest to PBPs 2 and 3.

Pharmacokinetic/Pharmacodynamic (PK/PD) relationship
Similar to other beta-lactam antimicrobial agents, the time that the plasma concentration of ertapenem 
exceeds the MIC of the infecting organism has been shown to best correlate with efficacy in 
pre-clinical PK/PD studies.

Mechanism of resistance
For species considered susceptible to ertapenem, resistance was uncommon in surveillance studies in 
Europe. In resistant isolates, resistance to other antibacterial agents of the carbapenem class was seen 
in some but not all isolates. Ertapenem is effectively stable to hydrolysis by most classes of beta-
lactamases, including penicillinases, cephalosporinases and extended spectrum beta-lactamases, but 
not metallo-beta-lactamases.

Methicillin-resistant staphylococci and enterococci are resistant to ertapenem, owing to PBP target 
insensitivity; P. aeruginosa and other non-fermentative bacteria are generally resistant, probably 
owing to limited penetration and to active efflux.

Resistance is uncommon in Enterobacteriaceae and ertapenem is generally active against those with 
extended-spectrum beta-lactamases (ESBLs). Resistance can however be observed when ESBLs or 
other potent beta-lactamases (e.g. AmpC types) are present in conjunction with reduced permeability, 
arising by the loss of one or more outer membrane porins, or with up-regulated efflux. Resistance can 
also arise via the acquisition of beta-lactamases with significant carbapenem-hydrolysing activity (e.g. 
IMP and VIM metallo-beta-lactamases or KPC types), though these are rare.

The mechanism of action of ertapenem differs from that of other classes of antibiotics, such as 
quinolones, aminoglycosides, macrolides and tetracyclines. There is no target-based cross-resistance 
between ertapenem and these substances. However, micro-organisms may exhibit resistance to more 
than one class of antibacterial agents when the mechanism is, or includes, impermeability to some 
compounds and/or an efflux pump.

Breakpoints

The EUCAST MIC breakpoints are as follows:

 Enterobacterales: S ≤ 0.5 mg/L and R > 0.5 mg/L
 Streptococcus pneumoniae: S ≤ 0.5 mg/L and R > 0.5 mg/L
 Haemophilus influenzae: S ≤ 0.5 mg/L and R > 0.5 mg/L
 M. catarrhalis: S ≤ 0.5 mg/L and R > 0.5 mg/L
 Gram negative anaerobes: S ≤ 0.5 mg/L and R > 0.5 mg/L
 Gram positive anaerobes: S ≤ 0.5 mg/L and R > 0.5 mg/L
 Viridans group streptococci: S ≤ 0.5 mg/L and R > 0.5 mg/L
 Non species related breakpoints: S ≤ 0.5 mg/L and R > 0.5 mg/L

 



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(NB: Susceptibility of staphylococci to ertapenem is inferred from methicillin susceptibility and 
susceptibility of group A, B, C,& G streptococci is inferred from benzylpenicillin susceptibility) 

The prescribers are informed that local MIC breakpoints, if available, should be consulted.

Microbiological susceptibility
The prevalence of acquired resistance may vary geographically and with time for selected species and 
local information on resistance is desirable, particularly when treating severe infections. Localised 
clusters of infections due to carbapenem-resistant organisms have been reported in the European 
Union. The information below gives only approximate guidance on the probability as to whether the 
micro-organism will be susceptible to ertapenem or not. 

Commonly susceptible species:
Gram-positive aerobes:
Methicillin-susceptible-staphylococci (including Staphylococcus aureus)*
Streptococcus agalactiae*
Streptococcus pneumoniae*†

Streptococcus pyogenes
Gram-negative aerobes:
Citrobacter freundii
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli*
Haemophilus influenzae*
Haemophilus parainfluenzae
Klebsiella oxytoca
Klebsiella pneumoniae*
Moraxella catarrhalis*
Morganella morganii
Proteus mirabilis*
Proteus vulgaris
Serratia marcescens
Anaerobes:
Clostridium species (excluding C. difficile)*
Eubacterium species*
Fusobacterium species*
Peptostreptococcus species*
Porphyromonas asaccharolytica*
Prevotella species*
Species for which acquired resistance may be a problem:
Gram-positive aerobes:
Methicillin-resistant staphylococci +#

Anaerobes:
Bacteroides fragilis and species in the B. fragilis Group*
Inherently resistant organisms:
Gram-positive aerobes:
Corynebacterium jeikeium
Enterococci including Enterococcus faecalis and Enterococcus faecium
Gram-negative aerobes:
Aeromonas species
Acinetobacter species
Burkholderia cepacia
Pseudomonas aeruginosa
Stenotrophomonas maltophilia
Anaerobes:
Lactobacillus species

 



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Others:
Chlamydia species
Mycoplasma species
Rickettsia species
Legionella species
* Activity has been satisfactorily demonstrated in clinical studies.
† The efficacy of INVANZ in the treatment of community acquired pneumonia due to penicillin-resistant 

Streptococcus pneumoniae has not been established.
+ frequency of acquired resistance > 50 % in some Member States.
# Methicillin-resistant staphylococci (including MRSA) are always resistant to beta-lactams.

Information from clinical studies

Efficacy in Paediatric Studies
Ertapenem was evaluated primarily for paediatric safety and secondarily for efficacy in randomised 
comparative, multicentre studies in patients 3 months to 17 years of age. 

The proportion of patients with a favourable clinical response assessment at posttreatment visit in the 
clinical MITT population is shown below:

Disease Stratum† Age Stratum
Ertapenem Ceftriaxone

n/m % n/m %
Community Acquired 
Pneumonia (CAP)

3 to 23 months 31/35 88.6 13/13 100.0

2 to 12 years 55/57 96.5 16/17 94.1
13 to 17 years 3/3 100.0 3/3 100.0

Disease Stratum Age Stratum
Ertapenem Ticarcillin/clavulanate

n/m % n/m %
Intraabdominal Infections (IAI) 2 to 12 years 28/34 82.4 7/9 77.8

13 to 17 years 15/16 93.8 4/6 66.7
Acute Pelvic Infections (API) 13 to 17 years 25/25 100.0 8/8 100.0
† This includes 9 patients in the ertapenem group (7 CAP and 2 IAI), 2 patients in the ceftriaxone group 

(2 CAP), and 1 patient with IAI in the ticarcillin/clavulanate group with secondary bacteraemia at entry into 
the study.

5.2 Pharmacokinetic properties

Plasma concentrations
Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 
1 g dose in healthy young adults (25 to 45 years of age) were 155 micrograms/mL (Cmax) at 0.5 hour 
postdose (end of infusion), 9 micrograms/mL at 12 hour postdose, and 1 microgram/mL at 24 hour 
postdose. 

Area under the plasma concentration curve (AUC) of ertapenem in adults increases nearly dose-
proportionally over the 0.5 to 2 g dose range.

There is no accumulation of ertapenem in adults following multiple intravenous doses ranging from 
0.5 to 2 g daily.

Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 
15 mg/kg (up to a maximum dose of 1 g) dose in patients 3 to 23 months of age were 
103.8 micrograms/mL (Cmax) at 0.5 hour postdose (end of infusion), 13.5 micrograms/mL at 6 hour 
postdose, and 2.5 micrograms/mL at 12 hour postdose. 

Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 
15 mg/kg (up to a maximum dose of 1 g) dose in patients 2 to 12 years of age were 

 



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113.2 micrograms/mL (Cmax) at 0.5 hour postdose (end of infusion), 12.8 micrograms/mL at 6 hour 
postdose, and 3.0 micrograms/mL at 12 hour postdose.

Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 
20 mg/kg (up to a maximum dose of 1 g) dose in patients 13 to 17 years of age were 
170.4 micrograms/mL (Cmax) at 0.5 hour postdose (end of infusion), 7.0 micrograms/mL at 12 hour 
postdose, and 1.1 microgram/mL at 24 hour postdose. 

Average plasma concentrations of ertapenem following a single 30 minute intravenous infusion of a 
1 g dose in three patients 13 to 17 years of age were 155.9 micrograms/mL (Cmax) at 0.5 hour postdose 
(end of infusion), and 6.2 micrograms/mL at 12 hour postdose.

Distribution
Ertapenem is highly bound to human plasma proteins. In healthy young adults (25 to 45 years of age), 
the protein binding of ertapenem decreases, as plasma concentrations increase, from approximately 
95 % bound at an approximate plasma concentration of < 50 micrograms/mL to approximately 92 % 
bound at an approximate plasma concentration of 155 micrograms/mL (average concentration 
achieved at the end of infusion following 1 g intravenously).

The volume of distribution (Vdss) of ertapenem in adults is approximately 8 litres (0.11 litre/kg) and 
approximately 0.2 litre/kg in paediatric patients 3 months to 12 years of age and approximately 
0.16 litre/kg in paediatric patients 13 to 17 years of age.

Concentrations of ertapenem achieved in adult skin blister fluid at each sampling point on the third 
day of 1 g once daily intravenous doses showed a ratio of AUC in skin blister fluid: AUC in plasma 
of 0.61.

In vitro studies indicate that the effect of ertapenem on the plasma protein binding of highly protein 
bound medicinal products (warfarin, ethinyl estradiol, and norethindrone) was small. The change in 
binding was < 12 % at peak plasma ertapenem concentration following a 1 g dose. In vivo, probenecid 
(500 mg every 6 hours) decreased the bound fraction of ertapenem in plasma at the end of infusion in 
subjects administered a single 1 g intravenous dose from approximately 91 % to approximately 87 %. 
The effects of this change are anticipated to be transient. A clinically significant interaction due to 
ertapenem displacing another medicinal product or another medicinal product displacing ertapenem is 
unlikely.

In vitro studies indicate that ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin 
or vinblastine and that ertapenem is not a substrate for P-glycoprotein-mediated transport.

Biotransformation
In healthy young adults (23 to 49 years of age), after intravenous infusion of radiolabelled 1 g 
ertapenem, the plasma radioactivity consists predominantly (94 %) of ertapenem. The major 
metabolite of ertapenem is the ring-opened derivative formed by dehydropeptidase-I-mediated 
hydrolysis of the beta-lactam ring.

In vitro studies in human liver microsomes indicate that ertapenem does not inhibit metabolism 
mediated by any of the six major CYP isoforms: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4.

Elimination
Following administration of a 1 g radiolabelled intravenous dose of ertapenem to healthy young adults 
(23 to 49 years of age), approximately 80 % is recovered in urine and 10 % in faeces. Of the 80 % 
recovered in urine, approximately 38 % is excreted as unchanged ertapenem and approximately 37 % 
as the ring-opened metabolite.

In healthy young adults (18 to 49 years of age) and patients 13 to 17 years of age given a 1 g 
intravenous dose, the mean plasma half-life is approximately 4 hours. The mean plasma half-life in 
children 3 months to 12 years of age is approximately 2.5 hours. Average concentrations of ertapenem 

 



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in urine exceed 984 micrograms/mL during the period 0 to 2 hours postdose and exceed 
52 micrograms/mL during the period 12 to 24 hours post-administration.

Special populations

Gender
The plasma concentrations of ertapenem are comparable in men and women.

Elderly
Plasma concentrations following a 1 g and 2 g intravenous dose of ertapenem are slightly higher 
(approximately 39 % and 22 %, respectively) in healthy elderly adults (≥ 65 years) relative to young 
adults ( 65 years). In the absence of severe renal impairment, no dosage adjustment is necessary in 
elderly patients.

Paediatric population
Plasma concentrations of ertapenem are comparable in paediatric patients 13 to 17 years of age and 
adults following a 1 g once daily intravenous dose.

Following the 20 mg/kg dose (up to a maximum dose of 1 g), the pharmacokinetic parameter values in 
patients 13 to 17 years of age were generally comparable to those in healthy young adults. To provide 
an estimate of the pharmacokinetic data if all patients in this age group were to receive a 1 g dose, the 
pharmacokinetic data were calculated adjusting for a 1 g dose, assuming linearity. A comparison of 
results show that a 1 g once daily dose of ertapenem achieves a pharmacokinetic profile in patients 
13 to 17 years of age comparable to that of adults. The ratios (13 to 17 years/adults) for AUC, the end 
of infusion concentration and the concentration at the midpoint of the dosing interval were 0.99, 1.20, 
and 0.84, respectively.

Plasma concentrations at the midpoint of the dosing interval following a single 15 mg/kg intravenous 
dose of ertapenem in patients 3 months to 12 years of age are comparable to plasma concentrations at 
the midpoint of the dosing interval following a 1 g once daily intravenous dose in adults (see Plasma 
concentrations). The plasma clearance (mL/min/kg) of ertapenem in patients 3 months to 12 years of 
age is approximately 2-fold higher as compared to that in adults. At the 15 mg/kg dose, the AUC value 
and plasma concentrations at the midpoint of the dosing interval in patients 3 months to 12 years of 
age were comparable to those in young healthy adults receiving a 1 g intravenous dose of ertapenem.

Hepatic impairment
The pharmacokinetics of ertapenem in patients with hepatic impairment have not been established. 
Due to the limited extent of hepatic metabolism of ertapenem, its pharmacokinetics are not expected to 
be affected by hepatic impairment. Therefore, no dosage adjustment is recommended in patients with 
hepatic impairment.

Renal impairment
Following a single 1 g intravenous dose of ertapenem in adults, AUCs of total ertapenem (bound and 
unbound) and of unbound ertapenem are similar in patients with mild renal impairment (Clcr 60 to 
90 mL/min/1.73 m2) compared with healthy subjects (ages 25 to 82 years). AUCs of total ertapenem 
and of unbound ertapenem are increased in patients with moderate renal impairment (Clcr 31 to 
59 mL/min/1.73 m2) approximately 1.5-fold and 1.8-fold, respectively, compared with healthy 
subjects. AUCs of total ertapenem and of unbound ertapenem are increased in patients with severe 
renal impairment (Clcr 5 to 30 mL/min/1.73 m

2) approximately 2.6-fold and 3.4-fold, respectively, 
compared with healthy subjects. AUCs of total ertapenem and of unbound ertapenem are increased in 
patients who require haemodialysis approximately 2.9-fold and 6.0-fold, respectively, between dialysis 
sessions, compared with healthy subjects. Following a single 1 g intravenous dose given immediately 
prior to a haemodialysis session, approximately 30 % of the dose is recovered in the dialysate. There 
are no data in paediatric patients with renal impairment.

 



14

There are inadequate data on the safety and efficacy of ertapenem in patients with advanced renal 
impairment and patients who require haemodialysis to support a dose recommendation. Therefore, 
ertapenem should not be used in these patients.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety, 
pharmacology, repeated-dose toxicity, genotoxicity and toxicity to reproduction and development. 
Decreased neutrophil counts, however, occurred in rats that received high doses of ertapenem, which 
was not considered a significant safety issue.

Long-term studies in animals to evaluate the carcinogenic potential of ertapenem have not been 
performed.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium bicarbonate (E500)
Sodium hydroxide (E524) to adjust pH to 7.5

6.2 Incompatibilities

Do not use solvents or infusion fluids containing dextrose for reconstitution or administration of 
ertapenem.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products except those mentioned in section 6.6.

6.3 Shelf life

2 years.

After reconstitution: Diluted solutions should be used immediately. If not used immediately, in use 
storage times are the responsibility of the user. Diluted solutions (approximately 20 mg/mL
ertapenem) are physically and chemically stable for 6 hours at room temperature (25°C) or for 
24 hours at 2 to 8°C (in a refrigerator). Solutions should be used within 4 hours of their removal from 
the refrigerator. Do not freeze solutions of INVANZ.

6.4 Special precautions for storage

Do not store above 25C.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

15 mL Type I glass vials with a grey butyl stopper and a white plastic cap on a coloured aluminium 
band seal.

Supplied in packs of 1 vial or 10 vials.

Not all pack sizes may be marketed. 

 



15

6.6 Special precautions for disposal and other handling

Instructions for use:

For single use only.

Reconstituted solutions should be diluted in sodium chloride 9 mg/mL (0.9 %) solution immediately 
after preparation.

Preparation for intravenous administration:
INVANZ must be reconstituted and then diluted prior to administration.

Adults and adolescents (13 to 17 years of age)
Reconstitution
Reconstitute the contents of a 1 g vial of INVANZ with 10 mL of water for injection or sodium 
chloride 9 mg/mL (0.9 %) solution to yield a reconstituted solution of approximately 100 mg/mL. 
Shake well to dissolve. (See section 6.4.)
Dilution
For a 50 mL bag of diluent: For a 1 g dose, immediately transfer contents of the reconstituted vial to a 
50 mL bag of sodium chloride 9 mg/mL (0.9 %) solution; or 

For a 50 mL vial of diluent: For a 1 g dose, withdraw 10 mL from a 50 mL vial of sodium chloride 
9 mg/mL (0.9 %) solution and discard. Transfer the contents of the reconstituted 1 g vial of INVANZ 
to the 50 mL vial of sodium chloride 9 mg/mL (0.9 %) solution. 
Infusion
Infuse over a period of 30 minutes.

Children (3 months to 12 years of age)
Reconstitution
Reconstitute the contents of a 1 g vial of INVANZ with 10 mL of water for injection or sodium 
chloride 9 mg/mL (0.9 %) solution to yield a reconstituted solution of approximately 100 mg/mL. 
Shake well to dissolve. (See section 6.4.)
Dilution
For a bag of diluent: Transfer a volume equal to 15 mg/kg of body weight (not to exceed 1 g/day) to a 
bag of sodium chloride 9 mg/mL (0.9 %) solution for a final concentration of 20 mg/mL or less; or 

For a vial of diluent: Transfer a volume equal to 15 mg/kg of body weight (not to exceed 1 g/day) to a 
vial of sodium chloride 9 mg/mL (0.9 %) solution for a final concentration of 20 mg/mL or less. 
Infusion
Infuse over a period of 30 minutes.

Compatibility of INVANZ with intravenous solutions containing heparin sodium and potassium 
chloride has been demonstrated.

The reconstituted solutions should be inspected visually for particulate matter and discolouration prior 
to administration, whenever the container permits. Solutions of INVANZ range from colourless to 
pale yellow. Variations of colour within this range do not affect potency.

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

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

 



16

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/02/216/001
EU/1/02/216/002

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 18 April 2002
Date of latest renewal: 22 December 2011

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.

 



17

ANNEX II

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT

 



18

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) responsible for batch release

Laboratoire Merck Sharp & Dohme – Chibret (Mirabel), Route de Marsat.
F-63963 Clermont-Ferrand Cedex 9, France.

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

The requirements for submission of periodic safety update reports 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)

Not applicable.

 



19

ANNEX III

LABELLING AND PACKAGE LEAFLET

 



20

A. LABELLING

 



21

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

INVANZ 1 g powder for concentrate for solution for infusion 
Ertapenem

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each vial contains: 1.0 g ertapenem (as sodium). 

3. LIST OF EXCIPIENTS

Sodium bicarbonate (E500); sodium hydroxide (E524) to adjust pH to 7.5.

4. PHARMACEUTICAL FORM AND CONTENTS

Powder for concentrate for solution for infusion
1 vial
10 vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 
Intravenous use after reconstitution and dilution. 
For single use only. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

Do not store above 25C

 



22

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

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/02/216/001 1 vial
EU/1/02/216/002 10 vials

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted.

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:

 



23

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

INVANZ 1 g powder for concentrate for solution for infusion
Ertapenem 
Intravenous use

2. METHOD OF ADMINISTRATION

Read the package leaflet before use. 
For single use only. 

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

1 g

6. OTHER

 



24

B. PACKAGE LEAFLET

 



25

Package Leaflet: information for the user

INVANZ 1 g powder for concentrate for solution for infusion 
ertapenem

Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, nurse or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What INVANZ is and what it is used for
2. What you need to know before you are given INVANZ
3. How to use INVANZ
4. Possible side effects
5. How to store INVANZ
6. Contents of the pack and other information

1. What INVANZ is and what it is used for

INVANZ contains ertapenem which is an antibiotic of the beta-lactam group. It has the ability to kill a 
wide range of bacteria (germs) that cause infections in various parts of the body. 

INVANZ can be given to persons 3 months of age and older.

Treatment:
Your doctor has prescribed INVANZ because you or your child has one (or more) of the following 
types of infection: 
 Infection in the abdomen
 Infection affecting the lungs (pneumonia)
 Gynaecological infections
 Skin infections of the foot in diabetic patients.

Prevention:
 Prevention of surgical site infections in adults following surgery of the colon or rectum.

2. What you need to know before you are given INVANZ

Do not use INVANZ
- if you are allergic to the active substance (ertapenem) or any of the other ingredients of this 

medicine (listed in section 6)
- if you are allergic to antibiotics such as penicillins, cephalosporins or carbapenems (which are 

used to treat various infections).

Warnings and precautions
Talk to your doctor, nurse or pharmacist before taking INVANZ.

During treatment, if you experience an allergic reaction (such as swelling of the face, tongue or throat, 
difficulty in breathing or swallowing, skin rash), tell your doctor straight away as you may need urgent 
medical treatment.

 



26

While antibiotics including INVANZ kill certain bacteria, other bacteria and fungi may continue to 
grow more than normal. This is called overgrowth. Your doctor will monitor you for overgrowth and 
treat you if necessary.

It is important that you tell your doctor if you have diarrhoea before, during or after your treatment
with INVANZ. This is because you may have a condition known as colitis (an inflammation of the 
bowel). Do not take any medicine to treat diarrhoea without first checking with your doctor.

Tell your doctor if you are taking medicines called valproic acid or sodium valproate (see Other 
medicines and INVANZ below).

Tell your doctor about any medical condition you have or have had including:
- Kidney disease. It is particularly important that your doctor knows if you have kidney disease 

and whether you undergo dialysis treatment.
- Allergies to any medicines, including antibiotics.
- Central nervous system disorders, such as localised tremors, or seizures.

Children and adolescents (3 months to 17 years of age)
Experience with INVANZ is limited in children less than two years of age. In this age group your 
doctor will decide on the potential benefit of its use. There is no experience in children under 3 months 
of age.

Other medicines and INVANZ
Always tell your doctor about all medicines that you are taking or plan to take, including those 
obtained without a prescription.

Tell your doctor, nurse or pharmacist if you are taking medicines called valproic acid or sodium 
valproate (used to treat epilepsy, bipolar disorder, migraines, or schizophrenia). This is because
INVANZ can affect the way some other medicines work. Your doctor will decide whether you should 
use INVANZ in combination with these other medicines.

Pregnancy and breast-feeding
It is important that you tell your doctor if you are pregnant or are planning to become pregnant before 
receiving INVANZ.

INVANZ has not been studied in pregnant women. INVANZ should not be used during pregnancy 
unless your doctor decides the potential benefit justifies the potential risk to the foetus.

It is important that you tell your doctor if you are breast-feeding or if you intend to breast-feed before 
receiving INVANZ.

Women who are receiving INVANZ should not breast-feed, because it has been found in human milk 
and the breast-fed baby may therefore be affected.

Driving and using machines
Do not drive or use any tools or machines until you know how you react to the medicine.
Certain side effects, such as dizziness and sleepiness, have been reported with INVANZ, which may 
affect some patients’ ability to drive or operate machinery.

INVANZ contains sodium
This medicine contains approximately 6.0 mEq (approximately 137 mg) of sodium per 1.0 g dose 
which should be taken into consideration by patients on a controlled sodium diet.

 



27

3. How to use INVANZ

INVANZ will always be prepared and given to you intravenously (into a vein) by a doctor or another 
healthcare professional.

The recommended dose of INVANZ for adults and adolescents 13 years of age and older is 1 gram (g) 
given once a day. The recommended dose for children 3 months to 12 years of age is 15 mg/kg given 
twice daily (not to exceed 1 g/day). Your doctor will decide how many days’ treatment you need.

For prevention of surgical site infections following surgery of the colon or rectum, the recommended 
dose of INVANZ is 1 g administered as a single intravenous dose 1 hour before surgery.

It is very important that you continue to receive INVANZ for as long as your doctor prescribes it.

If you are given more INVANZ than you should

If you are concerned that you may have been given too much INVANZ, contact your doctor or another 
healthcare professional immediately.

If you miss a dose of INVANZ

If you are concerned that you may have missed a dose, contact your doctor or another healthcare 
professional immediately.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Adults 18 years of age and older:

Since the drug has been marketed, severe allergic reactions (anaphylaxis), hypersensitivity syndromes 
(allergic reactions including rash, fever, abnormal blood tests) have been reported. The first signs of a 
severe allergic reaction may include swelling of the face and/or throat. If these symptoms occur tell 
your doctor straight away as you may need urgent medical treatment.

The most common (more than 1 in 100 patients and less than 1 in 10 patients) side effects are:
 Headache
 Diarrhoea, nausea, vomiting
 Rash, itching
 Problems with the vein into which the medicine is given (including inflammation, formation of 

a lump, swelling at the injection site, or leaking of fluid into the tissue and skin around the 
injection site)

 Increase in platelet count
 Changes in liver function tests

Less common (more than 1 in 1,000 patients and less than 1 in 100 patients) side effects are:
 Dizziness, sleepiness, sleeplessness, confusion, seizure
 Low blood pressure, slow heart rate
 Shortness of breath, sore throat
 Constipation, yeast infection of the mouth, antibiotic-associated diarrhoea, acid regurgitation, 

dry mouth, indigestion, loss of appetite
 Skin redness
 Vaginal discharge and irritation
 Abdominal pain, fatigue, fungal infection, fever, oedema/swelling, chest pain, abnormal taste
 Changes in some laboratory blood and urine tests

 



28

Side effects reported rarely (more than 1 in 10,000 patients and less than 1 in 1,000 patients) are:
 Decrease in white blood cells, decrease in blood platelet count
 Low blood sugar
 Agitation, anxiety, depression, tremor
 Irregular heart rate, increased blood pressure, bleeding, fast heart rate
 Nasal congestion, cough, bleeding from the nose, pneumonia, abnormal breathing sounds, 

wheezing
 Inflammation of the gall bladder, difficulty in swallowing, faecal incontinence, jaundice, liver 

disorder
 Inflammation of the skin, fungal infection of the skin, skin peeling, infection of the wound after 

an operation 
 Muscle cramp, shoulder pain
 Urinary tract infection, kidney impairment
 Miscarriage, genital bleeding
 Allergy, feeling unwell, pelvic peritonitis, changes to the white part of the eye, fainting.

Side effects reported (frequency not known) since the drug has been marketed are: 
 hallucinations
 decreased consciousness
 altered mental status (including aggression, delirium, disorientation, mental status changes) 
 abnormal movements 
 muscle weakness
 unsteady walking
 teeth staining

There have also been reports of changes in some laboratory blood tests.

If you experience raised or fluid-filled skin spots over a large area of your body, tell your doctor or 
nurse straight away.

Children and adolescents (3 months to 17 years of age):

The most common (more than 1 in 100 patients and less than 1 in 10 patients) side effects are:
 Diarrhoea
 Diaper rash
 Pain at the infusion site
 Changes in white blood cell count
 Changes in liver function tests

Less common (more than 1 in 1,000 patients and less than 1 in 100 patients) side effects are:
 Headache
 Hot flush, high blood pressure, red or purple, flat, pinhead spots under the skin
 Discoloured faeces, black tar-like faeces
 Skin redness, skin rash
 Burning, itching, redness and warmth at infusion site, redness at injection site
 Increase in platelet count 
 Changes in some laboratory blood tests

Side effects reported (frequency not known) since the drug has been marketed are:
 Hallucinations
 Altered mental status (including aggression) 

 



29

Reporting of side effects
If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store INVANZ

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 container.
The first 2 numbers indicate the month; the next 4 numbers indicate the year.

Do not store above 25C

6. Contents of the pack and other information

What INVANZ contains
The active ingredient of INVANZ is ertapenem 1 g.
The other ingredients are: sodium bicarbonate (E500) and sodium hydroxide (E524).

What INVANZ looks like and contents of the pack
INVANZ is a white to off-white, freeze-dried powder for concentrate for solution for infusion.
Solutions of INVANZ range from colourless to pale yellow. Variations of colour within this range do 
not affect potency.

INVANZ is supplied in packs of 1 vial or 10 vials.
Not all pack sizes may be marketed. 

Marketing Authorisation Holder Manufacturer
Merck Sharp & Dohme B.V. Laboratoires Merck Sharp & Dohme – Chibret
Waarderweg 39 Route de Marsat - Riom
2031 BN Haarlem F-63963 Clermont-Ferrand Cedex 9
The Netherlands France

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

Belgique/België/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel:+32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel. + 370 5 278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +361 888 53 00
hungary_msd@merck.com

 

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


30

Danmark
MSD Danmark ApS
Tlf: +45 44 82 40 00
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
INFECTOPHARM 
Arzneimittel und Consilium GmbH
Tel. +49 (0)6252 / 95-7000
kontakt@infectopharm.com

Nederland 
Merck Sharp & Dohme BV
Tel: 0800 9999000 
(+31 (0)23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: + 30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp.z o.o.
Tel.: +48 22 549 51 00
msdpolska@merck.com

France
MSD France
Tél: + 33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: + 4021 529 29 00
msdromania@merck.com

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 2998700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: + 386 1 5204201
msd_slovenia@merck.com

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak@merck.com

Ιtalia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0) 9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ.: 80000 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 (0)77 5700488
medicinskinfo@merck.com

 



31

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364 224
msd_lv@merck.com

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.
---------------------------------------------------------------------------------------------------------------------------
The following information is intended for medical or healthcare professionals only:

Instructions of how to reconstitute and dilute INVANZ:

For single use only.

Preparation for intravenous administration:
INVANZ must be reconstituted and then diluted prior to administration.

Adult and adolescents (13 to 17 years of age)
Reconstitution
Reconstitute the contents of a 1 g vial of INVANZ with 10 mL of water for injection or sodium 
chloride 9 mg/mL (0.9 %) solution to yield a reconstituted solution of approximately 100 mg/mL. 
Shake well to dissolve.
Dilution
For a 50 mL bag of diluent: For a 1 g dose, immediately transfer contents of the reconstituted vial to a 
50 mL bag of sodium chloride 9 mg/mL (0.9 %) solution; or

For a 50 mL vial of diluent: For a 1 g dose, withdraw 10 mL from a 50 mL vial of sodium chloride 
9 mg/mL (0.9 %) solution and discard. Transfer the contents of the reconstituted 1 g vial of INVANZ 
to the 50 mL vial of sodium chloride 9 mg/mL (0.9 %) solution.
Infusion
Infuse over a period of 30 minutes.

Children (3 months to 12 years of age)
Reconstitution
Reconstitute the contents of a 1 g vial of INVANZ with 10 mL of water for injection or sodium 
chloride 9 mg/mL (0.9 %) solution to yield a reconstituted solution of approximately 100 mg/mL. 
Shake well to dissolve.
Dilution
For a bag of diluent: Transfer a volume equal to 15 mg/kg of body weight (not to exceed 1 g/day) to a 
bag of sodium chloride 9 mg/mL (0.9 %) solution for a final concentration of 20 mg/mL or less; or

For a vial of diluent: Transfer a volume equal to 15 mg/kg of body weight (not to exceed 1 g/day) to a 
vial of sodium chloride 9 mg/mL (0.9 %) solution for a final concentration of 20 mg/mL or less.
Infusion
Infuse over a period of 30 minutes.

The reconstituted solution should be diluted in sodium chloride 9 mg/mL (0.9 %) solution 
immediately after preparation. Diluted solutions should be used immediately. If not used immediately, 
in use storage times are the responsibility of the user. Diluted solutions (approximately 20 mg/mL
ertapenem) are physically and chemically stable for 6 hours at room temperature (25°C) or for 
24 hours at 2 to 8°C (in a refrigerator). Solutions should be used within 4 hours of their removal from 
the refrigerator. Do not freeze the reconstituted solutions.

 



32

The reconstituted solutions should be inspected visually for particulate matter and discolouration prior 
to administration, whenever the container permits. Solutions of INVANZ range from colourless to 
pale yellow. Variations of colour within this range do not affect potency.

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

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET