PRIMAXIN IV Powder for solution for infusion Ref.[10486] Active ingredients: Cilastatin Imipemide Imipenem and Cilastatin

Posology

The dose recommendations for PRIMAXIN represent the quantity of imipenem/cilastatin to be administered.

The daily dose of PRIMAXIN should be based on the type of infection and given in equally divided doses based on consideration of degree of susceptibility of the pathogen(s) and the patient’s renal function (see also section 4.4 and 5.1).

Adults and adolescents

For patients with normal renal function (creatinine clearance of ≥90 ml/min), the recommended dose regimens are:

500 mg/500 mg every 6 hours OR

1000 mg/1000 mg every 8 hours OR every 6 hours

It is recommended that infections suspected or proven to be due to less susceptible bacterial species (such as Pseudomonas aeruginosa) and very severe infections (e.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. The total daily dose (i.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:

Patients with a creatinine clearance of <15 ml/min

These patients should not receive PRIMAXIN 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 PRIMAXIN after haemodialysis and at 12 hour intervals timed from the end of that haemodialysis session. Dialysis patients, especially those with background central nervous system (CNS) disease, should be carefully monitored; for patients on haemodialysis, PRIMAXIN is recommended only when the benefit outweighs the potential risk of seizures (see section 4.4).

Currently there are inadequate data to recommend use of PRIMAXIN for patients on peritoneal dialysis.

Hepatic impairment

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

Elderly population

No dose adjustment is required for the elderly patients with normal renal function (see section 5.2).

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.

It is recommended that infections suspected or proven to be due to less susceptible bacterial species (such as Pseudomonas aeruginosa) and very severe infections (e.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 4.4.

Method of administration

PRIMAXIN is to be reconstituted and further diluted (see section 6.2, 6.3 and 6.6) 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.

Symptoms of overdose that can occur are consistent with the adverse reaction profile; these may include seizures, confusion, tremors, nausea, vomiting, hypotension, bradycardia. No specific information is available on treatment of overdose with PRIMAXIN. Imipenem-cilastatin sodium is haemodialyzable. However, usefulness of this procedure in the overdose setting is unknown.

2 years.

After reconstitution: Diluted solutions should be used immediately. The time interval between the beginning of reconstitution and the end of intravenous infusion should not exceed two hours.

Do not store above 25°C.

Do not freeze the reconstituted solution.

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

20 ml Type I glass vials.

The medicinal product is supplied in packs of 1 vial, 10 vials and 25 vials.

Not all pack sizes may be marketed.

Each vial is for single use only.

Reconstitution

Contents of each vial must be transferred to 100 ml of an appropriate infusion solution (see sections 6.2 and 6.3): 0.9% sodium chloride. In exceptional circumstances where 0.9% sodium chloride cannot be used for clinical reasons 5% glucose may be used instead.

A suggested procedure is to add approximately 10 ml of the appropriate infusion solution to the vial. Shake well and transfer the resulting mixture to the infusion solution container.

CAUTION: THE MIXTURE IS NOT FOR DIRECT INFUSION.

Repeat with an additional 10 ml of infusion solution to ensure complete transfer of vial contents to the infusion solution. The resulting mixture should be agitated until clear.

The concentration of the reconstituted solution following the above procedure is approximately 5 mg/ml for both imipenem and cilastatin.

Variations of colour, from colourless to yellow, do not affect the potency of the product.

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