IMIPENEM-CILASTATIN

Posology The dose recommendations for Imipenem/Cilastatin Kabi 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. Patients with 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.

Table 1:

Creatinine Clearance (mL/min) is: If TOTAL DAILY DOSE is: 2000 mg/day If TOTAL DAILY DOSE is: 3000 mg/day If TOTAL DAILY DOSE is: 4000 mg/day ≥90 500 1000 1000 (normal) q6h q8h 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 Kabi unless haemodialysis is instituted within 48 hours.

Patients on haemodialysis When treating patients with creatinine clearances of <15 ml/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 Kabi 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 Kabi for patients on peritoneal dialysis.

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

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.

6. 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. 4 “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, patient 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.

Patients with creatinine clearances of <15 ml/min 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 […]

g. g. penicillins or cephalosporins).