IMIPENEM/CILASTATIN

Posology The dose recommendations for Imipenem/cilastatin represent the quantity of imipenem/cilastatin to be administered. 1). g. in neutropenic patients with a fever) should be treated with 1000 mg/1000 mg administered every 6 hours.

A reduction in dose is necessary when creatinine clearance is ≤ 90 ml/min. (see Table 1). The maximum total daily dose should not exceed 4000 mg/4000 mg per day Renal impairment To determine the reduced dose for adults with impaired renal function: 1.

e. 2000/2000, 3000/3000 or 4000/4000 mg) that would usually be applicable to patients with normal renal function should be selected. 2. From table 1, the appropriate reduced dose regimen is selected according to the patient's creatinine clearance.

For infusion times see Method of administration. If TOTAL DAILY DOSE is: 2000 mg/day If TOTAL DAILY DOSE is: 3000 mg/day IF TOTAL DAILY DOSE is: 4000 mg/day Creatinine clearance (mL/min) is: ≥90 (normal) 500 q6h 1000 q8h 1000 q6h reduced dosage (mg) for patients with renal impairment: <90 - ≥60 400 q6h 500 q6h 750 q8h <60 - ≥30 300 q6h 500 q8h 500 q6h <30 - ≥15 200 q6h 500 q12h 500 q12h Patients with a creatinine clearance of ≤15 ml/min These patients should not receive Imipenem/cilastatin unless haemodialysis is instituted within 48 hours.

Patients on haemodialysis When treating patients with creatinine clearances of ≤ 15ml/min who are undergoing dialysis use the dose recommendation for patients with creatinine clearances of 15 to 29 ml/min (see table 1). Both imipenem and cilastatin are cleared from the circulation during haemodialysis .

The patient should receive Imipenem/cilastatin after haemodialysis and at 12 hour intervals timed from the end of that haemodialysis session. 4). Currently there are inadequate data to recommend use of Imipenem/cilastatin for patients on peritoneal dialysis.

2). 2). Paediatric population ≥ 1 year of age For paediatric patients ≥ 1 year of age, the recommended dose is 15 or 25 mg/kg/dose administered every 6 hours. g. in neutropenic patients with a fever) should be treated with 25 mg/kg administered every 6 hours.

Paediatric population <1 year of age Clinical data are insufficient to recommend dosing for children less than 1 year of age. Paediatric population with renal impairment Clinical data are insufficient to recommend dosing for paediatric patients with renal impairment (serum creatinine > 2 mg/dl).

See section

2%). 2%). Increases in serum transaminases and in alkaline phosphatase are also commonly reported. The following adverse reactions have been reported in clinical studies or during post- marketing experience.

All adverse reactions are listed under system organ class and frequency:

Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), Rare (≥ 1/10,000 to < 1/1,000), Very rare (< 1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

g. exanthematous) Uncommon urticaria, pruritus Rare toxic epidermal necrolysis, angioedema, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis Skin and subcutaneous tissue disorders Very rare hyperhidrosis, skin texture changes Musculoskeletal and connective tissue disorders Very rare polyarthralgia, thoracic spine pain Renal and urinary disorders Rare acute renal failure, oligurial/anuria, polyuria, urine discoloration (harmless and should not be confused with haematuria).

The role of Imipenem/cilastatin in changes in renal function is difficult to assess, since factors predisposing to pre-renal azotemia or to impaired renal function usually have been present. Reproductive system ad breast disorders Very rare pruritus vulvae Uncommon fever, local pain and induration at the injection site, erythema at the injection siteGeneral disorders and administration site condition Very rare Chest discomfort, asthenia/weakness common increases in serum transaminases, increases in serum alkaline phosphatase Investigations Uncommon A positive direct Coombs´test, prolonged prothrombin time, decreased haemoglobin, increases in serum bilirubin, elevations in serum creatinine, elevations in blood urea nitrogen Paediatric population (≥ 3 months of age) In studies of 178 paediatric patients ≥ 3 months of age, the reported adverse reactions were consistent with those reported for adults.

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. uk/yellowcard

4. 6) prior to administration. Each dose of ≤ 500 mg/500 mg should be given by intravenous infusion over 20 to 30 minutes. Each dose > 500 mg/500 mg should be infused over 40 to 60 minutes. In patients who develop nausea during the infusion, the rate of infusion may be slowed.

1. g. g. penicillins or cephalosporins). 4 Special warnings and precautions for use General The selection of imipenem/cilastatin to treat an individual patient should take into account the appropriateness of using a carbapenem antibacterial agent based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial agents and the risk of selecting for carbapenem-resistant bacteria.

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.

3). If an allergic reaction to imipenem/cilastatin occurs, discontinue the therapy immediately. Serious anaphylactic reactions require immediate emergency treatment. Hepatic Hepatic function should be closely monitored during treatment with imipenem/cilastatin due to the risk of hepatic toxicity (such as increase in transaminases, hepatic failure and fulminant hepatitis).

Use in patients with liver disease: patients with pre-existing liver disorders should have liver function monitored during treatment with Imipenem/cilastatin. 2). Haematology A positive direct or indirect Coombs test may develop during treatment with imipenem/cilastatin.

Antibacterial spectrum The antibacterial spectrum of imipenem/cilastatin should be taken into account especially in life-threatening conditions before embarking on any empiric treatment. g. bacterial skin and soft-tissue infections, to imipenem/cilastatin, caution should be exercised.

The use of imipenem/cilastatin is not suitable for treatment of these types of infections unless the pathogen is already documented and known to be susceptible or there is a very high suspicion that the most likely pathogen(s) would be suitable for treatment.

Concomitant use of an appropriate anti-MRSA agent may be indicated when MRSA infections are suspected or proven to be involved in the approved indications. 1). 5). Clostridium difficile Antibiotic-associated colitis and pseudomembranous colitis have been reported with imipenem/cilastatin and with nearly all other anti-bacterial agents and may range from mild to life-threatening in severity.

8). Discontinuation of therapy with imipenem/cilastatin and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given. Meningitis Imipenem/cilastatin is not recommended for the therapy of meningitis.

Renal impairment Imipenem/cilastatin accumulates in patients with reduced kidney function. 2 and the subheading “Central nervous system” in this section. Central nervous system CNS adverse reactions such as myoclonic activity, confusional states, or seizures have been reported, especially when recommended doses based on renal function and body weight were exceeded.

g. brain lesions or history of seizures) and/or compromised renal function in whom accumulation of the administered entities could occur. 2). Anticonvulsant therapy should be continued in patients with a known seizure disorder. Special awareness should be made to neurological symptoms or convulsions in children with known risk factors for seizures, or on concomitant treatment with medicinal products lowering the seizures threshold.

If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically and placed on anticonvulsant therapy if not already instituted. If CNS symptoms continue, the dose of Imipenem/cilastatin should be decreased or discontinued.

73 m2 should not receive Imipenem/cilastatin unless haemodialysis is instituted within 48 hours. 2). Paediatric population Clinical data are insufficient to recommend the use of Imipenem/cilastatin in children under 1 year of age or paediatric patients with impaired renal function (serum creatinine >2 mg/dl).

See also above under Central nervous […]

1. g. g. penicillins or cephalosporins).