RENAPIME Powder for solution for injection / infusion Ref.[6584] Active ingredients: Cefepime

Renapime can be administered via intravenous use or intramuscular use.

After reconstitution, the solution is yellow to yellow-brown.

The usual dose and the route of administration vary in accordance with the severity of the infection, the renal function and the general conditions of the patient.

The IV route of administration is preferable in the patients with severe infections or in a life-threatening situation, particularly if there is the possibility of shock.

Adults and children weighing >40 kg with normal renal function

The usual treatment duration is 7 to 10 days; more severe infections can require a more prolonged treatment. In the empirical treatment of febrile neutropenia, the usual treatment duration should not be less than 7 days or until the resolution of the neutropenia.

In patients weighing ≤40 kg, the posology indicated for the children is recommended.

Elderly

No dose adjustment is required in patients with normal renal function; the dose adjustment is recommended in patients with impaired renal function (see section 4.4).

Adults with renal insufficiency

The cefepime dose should be adjusted to compensate the slower renal elimination rate. In adult patients with mild to moderate renal insufficiency, the initial dose of cefepime recommended should be the same as for patients with normal renal function. The recommended maintenance dose should be in accordance with the instructions of the table below.

When only the serum creatinine values are available, the (Cockcroft and Gault) formula can be used to calculate the creatinine clearance. The serum creatinine should represent a steady-state of renal function:

Man: Creatinine clearance (ml/min) = weight (kg) x (140 – age) / 72 x serum creatinine (mg/dl)

Woman: 0.85 x value calculated using the man formula

* The pharmacokinetic models indicate that it is necessary to reduce the dose in these patients. In patients receiving cefepime and doing haemodialysis, the dose is 1 gram as loading dose in the first day of treatment followed by 500 mg daily for all the infections, except febrile neutropenia which is 1 gram daily. In the dialysis days, cefepime should be administered after dialysis. Cefepime should be administered, whenever possible, at the same time every day.

Patients doing dialysis

In the patient doing dialysis, about 68% of the total quantity of cefepime present in the body in the beginning of the dialysis will be removed during a 3 hour dialysis. In the patient doing continuous ambulatory peritoneal dialysis, cefepime can be administered in the same dosages that are recommended for the patients with normal renal function, i.e. 500 mg, 1 g or 2 g, depending on the severity of the infection, but with an interval of 48 hours between doses.

Children with normal renal function

In the child, the usual recommended dose is:

Pneumonia, urinary tract infection, skin and subcutaneous tissue infection:

Children aged more than 2 months and weighing ≤40 kg: 50 mg/kg every 12 hours for 10 days; in more severe infections, 8 hours interval between the intakes should be done.

Bacteraemia that occurs in association with infections, bacterial meningitis and empirical treatment of febrile neutropenia:

Children aged more than 2 months and weighing ≤40 kg: 50 mg/kg every 8 hours for 7 to 10 days.

The experience in children aged less than 2 months is limited. Despite the experience having been obtained with the 50 mg/kg dose, data from pharmacokinetic models obtained in children aged more than 2 months suggest that, in children from 1 month to 2 months old, a dose of 30 mg/kg every 12 or 8 hours can be considered. The administration of Renapime in these patients should be carefully monitored.

In the child weighing >40 kg, it is recommended to use the dose indicated for adults. The maximum recommended dose for adults (2 g every 8 hours) should not be exceeded. The experience with the intramuscular use in children is limited.

Children with renal insufficiency

As renal excretion is the main route of elimination of cefepime, the dose should be adjusted in children with renal insufficiency. A dose of 50 mg/kg in children from 2 months to 12 year old and a dose 30 mg/kg in children 1 month to 2 months are comparable to a 2 g dose in the adult.

The same interval between the doses is recommended or the same dose reduction indicated for the renal insufficient adult.

Patients with hepatic function impairment

No dose adjustment is required in patients with hepatic insufficiency.

In case of severe overdose, especially in patients with renal function impairment, haemodialysis can help remove cefepime from the body (peritoneal dialysis is not useful).

Accidental overdose occurred with the administration of high doses to patients with decreased renal function (see sections 4.2 and 4.4).

Medicinal product in the original container: 3 years.

Reconstituted solution for injection, reconstituted with water for injections:

The in use physical and chemical stability was demonstrated for 18 hours at room temperature (15-25°C) and for 7 days in a refrigerator (2-8°C).

From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use time and storage conditions prior to administration are users' responsibility and, usually, should not exceed 24 hours at 2°-8°C, unless reconstitution has occurred under validated aseptic controlled conditions.

The reconstituted solution for infusion, reconstituted with other solvents (sodium chloride 0.9 solution, sodium chloride 0.9% with glucose 5% solution, glucose 5% or 10% solution, Ringer lactate solution, Ringer lactate with glucose 5% solution, Sodium lactate 1/6M solution):

The in use physical and chemical stability was demonstrated for 4 hours at room temperature (15-25°C).

Do not refrigerate.

From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use time and storage conditions prior to administration are users' responsibility, unless reconstitution has occurred under validated aseptic controlled conditions.

This medicinal product does not require any special temperature storage conditions.

Keep the container in the outer carton.

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

Colourless type II 20 ml glass vial closed with chlorobutyl rubber stopper and sealed with an aluminium cap and a plastic flip-off.

Pack size: 1, 5, 10, 20, 25, 50 and 100 vials.

Not all pack sizes may be marketed.

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

Preparation and administration of the reconstituted solution:

Renapime, powder for solution for injection/infusion should be dissolved in:

a) water for injections

or in one of the solutions listed in b) below for intravenous administration

b) sodium chloride 0.9% solution
sodium chloride 0.9% with glucose 5% solution
glucose 5% or 10% solution
Ringer lactate solution
Ringer lactate with glucose 5% solution
sodium lactate 1/6 M solution.

For Intravenous Injection, the volume of the solvent to be added to each vial and the resulting concentration of cefepime are presented in the following table:

For Intravenous Infusion, the volume of the solvent for infusion (solution listed in b)) to be used for reconstitution and the resulting concentration of cefepime are presented in the following table:

The volume of the solvent for infusion to be used for each vial and the resulting concentration of cefepime are presented in the following table:

The resulting solution should be administered over approximately 30 minutes.

For Intramuscular Injection, reconstitute the 1 g vial by using 3.0 ml of water for injections.

Note:

The reconstituted solutions, which are prepared correctly, can present a yellow to yellow-brown colour. This does not mean that efficacy of Renapime may be compromised.

The content of the vial is meant for a single usage. The remaining reconstituted solution should be discarded.

Inspect the vial before using. It can only be used if the solution does not present particles.