Product Description

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. Before initiating therapy with IMIPENAM/CILASTATIN, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems,penicillins, cephalosporins, other beta-lactams and other allergens (see section 4.3). If an allergic reaction to IMIPENAM/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. There is no dose adjustment necessary (see section 4.2).

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. Furthermore, due to the limited susceptibility of specific pathogens associated with e.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. Concomitant use of an aminoglycoside may be indicated when Pseudomonas aeruginosa infections are suspected or proven to be involved in the approved indications (see section 4.1).

Interaction with valproic acid

The concomitant use of imipenem/cilastatin and valproic acid/sodium valproate is not recommended (see section 4.5).

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. It is important to consider this diagnosis in patients who develop diarrhoea during or after the use of imipenem/cilastatin (see section 4.8). 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

IMIPENAM/CILASTATIN is not recommended for the therapy of meningitis.

Renal impairment

Imipenem-cilastatin accumulates in patients with reduced kidney function. CNS adverse reactions may occur if the dose is not adjusted to the renal function, see section 4.2 and 4.4 “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. These experiences have been reported most commonly in patients with CNS disorders (e.g. brain lesions or history of seizures) and/or compromised renal function in whom accumulation of the administered entities could occur. Hence close adherence to recommended dose schedules is urged especially in these patients (see section 4.2). 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 IMIPENAM/CILASTATIN should be decreased or discontinued.

Patients with creatinine clearances of <15 ml/min should not receive IMIPENAM/CILASTATIN unless haemodialysis is instituted within 48 hours. For patients on haemodialysis, IMIPENAM/CILASTATIN is recommended only when the benefit outweighs the potential risk of seizures (see section 4.2).

Paediatric population

Clinical data are insufficient to recommend the use of IMIPENAM/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 system.

IMIPENAM/CILASTATIN 500 mg/500 mg contains 37.6 mg of sodium (1.6 mEq) which should be taken into consideration by patients on a controlled sodium diet.