'Imipenem and Cilastatin Sodium' IV 500 mg Injection contains 500 mg imipenem (as the monohydrate) with 500 mg cilastatin (as the sodium salt).

Powder for concentrate for solution for infusion.

'Imipenem and Cilastatin Sodium' IV is available as vials containing sterile white to light yellow powder.

Broad spectrum beta lactam antibiotic.

'Imipenem and Cilastatin Sodium' contains:

imipenem, a member of a class of beta lactam antibiotics the thienamycins

cilastatin sodium, a specific enzyme inhibitor, that blocks the metabolism of imipenem in the kidney and substantially increases the concentration of unchanged imipenem in the urinary tract.

'Imipenem and Cilastatin Sodium' is bactericidal against an unusually wide spectrum of Gram positive, Gram negative, aerobic and anaerobic pathogens. 'Imipenem and Cilastatin Sodium' is useful for treating single and polymicrobic infections, and initiating therapy prior to identification of the causative organisms.

'Imipenem and Cilastatin Sodium' is indicated for the treatment of the following infections due to susceptible organisms:

'Imipenem and Cilastatin Sodium' IV

Lower respiratory tract infections

Intra abdominal infections

Genito urinary infections

Gynaecological infections

Septicaemia

Bone and joint infections

Skin and soft tissue infections

Note: 'Imipenem and Cilastatin Sodium' is not indicated against central nervous system infections.

'Imipenem and Cilastatin Sodium' is indicated against mixed infections caused by susceptible aerobic and anaerobic bacteria. The majority of these infections are associated with contamination by faecal flora, or flora originating from the vagina, skin, and mouth. In these mixed infections, 'Imipenem and Cilastatin Sodium' is usually effective against Bacteroides fragilis sp., the most commonly encountered anaerobic pathogen, which is usually resistant to the aminoglycosides, cephalosporins and penicillins.

Consideration should be given to official local guidance (e.g. national recommendations) on the appropriate use of bacterial agents.

Susceptibility of the causative organism to the treatment should be tested (if possible), although therapy may be initiated before the results are available.

Prophylaxis: 'Imipenem and Cilastatin Sodium' IV is also indicated for the prevention of certain post operative infections in patients undergoing contaminated or potentially contaminated surgical procedures or where the occurrence of post operative infection could be especially serious.

The total daily dosage and route of administration of 'Imipenem and Cilastatin Sodium' should be based on the type or severity of infection, consideration of degree of susceptibility of the pathogen(s), renal function and bodyweight. Doses cited are based on a bodyweight of >70 kg. The total daily requirement should be given in equally divided doses.

The dosage recommendations that follow specify the amounts of imipenem to be given. An equivalent amount of cilastatin is provided with this. One vial of 'Imipenem and Cilastatin Sodium' IV 500 mg provides the equivalent of 500 mg anhydrous imipenem and 500 mg cilastatin.

Use in the elderly

Age does not usually affect the tolerability and efficacy of 'Imipenem and Cilastatin Sodium'. The dosage should be determined by the severity of the infection, the susceptibility of the causative organism(s), the patient's clinical condition, and renal function.

INTRAVENOUS ADMINISTRATION

This formulation should not be used intramuscularly. The dosage of 'Imipenem and Cilastatin Sodium' IV should be determined by the severity of the infection, the antibiotic susceptibility of the causative organism(s) and the condition of the patient.

Note: All recommended doses refer to the imipenem fraction of 'Imipenem and Cilastatin Sodium'.

Adults (based on 70 kg bodyweight): The usual adult daily dosage is 1 2 g administered in 3 4 equally divided doses (see chart below). In infections due to less sensitive organisms, the daily dose may be increased to a maximum dose of 50 mg/kg/day (not exceeding 4 g daily).

Usual adult intravenous dosage

Each dose of 250 mg or 500 mg should be given by intravenous infusion over 20 30 minutes. Each dose of 1000 mg should be infused over 40 60 minutes. In patients who develop nausea during infusion, the infusion rate may be slowed.

Imipenem and Cilastatin Sodium' has been used successfully as monotherapy in immunocompromised cancer patients for confirmed or suspected infections such as sepsis.

Prophylactic use

For prophylaxis against post surgical infections in adults, 1 g 'Imipenem and Cilastatin Sodium' IV should be given intravenously on induction of anaesthesia and 1 g three hours later. For high risk (i.e. colorectal) surgery, two additional 0.5 g doses can be given at 8 and 16 hours after induction.

In patients with renal insufficiency

As in patients with normal renal function, dosing is based on the severity of the infection. The maximum dosage for patients with various degrees of renal functional impairment is shown in the following table. Doses cited are based on a bodyweight of 70 kg. Proportionate reduction in dose administered should be made for patients with lower bodyweight.

Maximum dosage in relation to renal function

* The higher dose should be reserved for infections caused by less susceptible organisms.

** Patients with creatinine clearance of 6 20 ml/min should be treated with 250 mg (or 3.5 mg/kg, whichever is lower) every 12 hours for most pathogens. When the 500 mg dose is used in these patients there may be an increased risk of convulsions.

Patients with a creatinine clearance of <5 ml/min should not receive 'Imipenem and Cilastatin Sodium' IV unless haemodialysis is started within 48 hours.

'Imipenem and Cilastatin Sodium' is cleared by haemodialysis. The patient should receive 'Imipenem and Cilastatin Sodium' IV immediately after haemodialysis and at 12 hourly intervals thereafter. Dialysis patients, especially those with background CNS disease, should be carefully monitored; patients on haemodialysis should receive 'Imipenem and Cilastatin Sodium' IV only when the benefit outweighs the potential risk of convulsions.

There are currently inadequate data to recommend the use of 'Imipenem and Cilastatin Sodium' IV for patients on peritoneal dialysis.

Paediatric dosage

The maximum daily dose should not exceed 2 g.

Children over 40 kg bodyweight should receive adult doses.

Clinical data are insufficient to recommend an optimal dose for children under 3 months of age or infants and children with impaired renal function.

'Imipenem and Cilastatin Sodium' IV is not recommended for the therapy of meningitis. If meningitis is suspected an appropriate antibiotic should be used.

'Imipenem and Cilastatin Sodium' IV may be used in children with sepsis as long as they are not suspected of having meningitis.