VISTIDE Concentrate for solution for infusion Ref.[6674] Active ingredients: Cidofovir

The therapy should be prescribed by a physician experienced in the management of HIV infection.

Before each administration of cidofovir, serum creatinine and urine protein levels should be investigated. It must be administered with oral probenecid and intravenous saline as described below (see section 4.4 for appropriate recommendations, and under section 6.6 for information on obtaining probenecid).

Posology

Adults

Induction treatment. The recommended dose of cidofovir is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hour) administered once weekly for two consecutive weeks.

Maintenance treatment. Beginning two weeks after the completion of induction treatment, the recommended maintenance dose of cidofovir is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hour) administered once every two weeks. Suspension of maintenance treatment with cidofovir should be considered in accordance with local recommendations for the management of HIV infected patients.

Elderly population

The safety and efficacy of cidofovir have not been established for the treatment of CMV disease in patients over 60 years of age. Since elderly individuals frequently have reduced glomerular function, particular attention should be paid to assessing renal function before and during administration of the medicinal product.

Renal insufficiency

Renal insufficiency [creatinine clearance ≤55 ml/min or ≥2+ proteinuria (≥100 mg/dl)] is a contraindication for the use of cidofovir (see sections 4.3 and 4.4).

Hepatic insufficiency

The safety and efficacy of cidofovir have not been established in patients with hepatic disease and therefore it should be used with caution in this patient population.

Paediatric population

The safety and efficacy of cidofovir in children below 18 years of age have not been established. No data are available. It is not recommended for use in children below 18 years of age.

Method of administration

Precautions to be taken before handling or administering the medicinal product:

Adequate precautions including the use of appropriate safety equipment are recommended for the preparation, administration and disposal of cidofovir. The preparation of cidofovir reconstituted solution should be done in a laminar flow biological safety cabinet. Personnel preparing the reconstituted solution should wear surgical gloves, safety glasses and a closed front surgical-type gown with knit cuffs. If cidofovir contacts the skin, wash membranes and flush thoroughly with water. (See section 6.6.)

Cidofovir 75 mg/ml Concentrate for Solution for Infusion is for intravenous infusion only. The recommended dose, frequency, or infusion rate must not be exceeded. It must be diluted in 100 millilitres 0.9% (normal) saline prior to administration. The entire volume should be infused intravenously into the patient at a constant rate over a period of 1 hour by use of a standard infusion pump. To minimise potential nephrotoxicity, oral probenecid and intravenous saline prehydration must be administered with each Cidofovir 75 mg/ml Concentrate for Solution for Infusion (see section 4.4).

Two cases of cidofovir overdose have been reported. In both cases, the overdose occurred during the first induction dose and no additional cidofovir therapy was administered. One patient received a single dose of 16.4 mg/kg and the other patient received a single dose of 17.3 mg/kg.

Symptoms

One of these patients experienced a minor transient change in renal function, while the other patient had no change in renal function (see section 4.4).

Management

Both patients were hospitalised and received prophylactic oral probenecid and vigorous hydration for 3 to 7 days.

Shelf life: 2 years.

From a microbiological point of view, the product must be used immediately.

Chemical and physical in-use stability has been demonstrated for up to 24 hours at 2-8°C when dilution is performed under controlled and validated aseptic conditions. Storage beyond 24 hours or freezing is not recommended. Refrigerated solutions should be allowed to warm to room temperature prior to use.

Do not store above 25°C. Do not refrigerate or freeze.

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

5 ml clear glass vials with a 5 ml nominal fill volume. The container/closure components include: Type I clear highly resistant borosilicate glass vials, Dark grey bromobutyl rubber stoppers, and aluminium seals with a flip off plastic tab. Each pack contains one 5 ml vial.

Cidofovir 75 mg/ml Concentrate for Solution for Infusion is supplied in single-use vials. Partially used vials should be discarded.

Method of preparation and administration

Cidofovir 75 mg/ml Concentrate for Solution for Infusion vials should be visually inspected for particulate matter and discolouration prior to administration.

With a syringe, transfer under aseptic conditions the appropriate dose of cidofovir from the vial to an infusion bag containing 100 ml 0.9% (normal) saline solution, and mix thoroughly. The entire volume should be infused intravenously into the patient at a constant rate over a period of 1 hour by use of a standard infusion pump. It should be administered by health care professionals adequately experienced in the care of AIDS patients.

The chemical and physical stability of Cidofovir 75 mg/ml Concentrate for Solution for Infusion admixed with saline has been demonstrated in glass bottles, in infusion bags composed of either polyvinyl chloride (PVC) or ethylene/propylene copolymer, and in PVC based vented IV administration sets. Other types of IV set tubing and infusion bags have not been studied.

Compatibility with Ringer’s Solution, Lactated Ringer’s Solution or bacteriostatic infusion fluids has not been evaluated.

Handling and disposal

Adequate precautions including the use of appropriate safety equipment are recommended for the preparation, administration and disposal of cidofovir. The preparation of cidofovir reconstituted solution should be done in a laminar flow biological safety cabinet. Personnel preparing the reconstituted solution should wear surgical gloves, safety glasses and a closed front surgical-type gown with knit cuffs. If cidofovir contacts the skin, wash membranes and flush thoroughly with water. Excess cidofovir and all other materials used in the admixture preparation and administration should be placed in a leak-proof, puncture-proof container for disposal. Any unused product or waste material should be disposed of in accordance with local requirements.

Obtaining probenecid

Probenecid is not supplied with cidofovir and should be obtained via the Marketing Authorisation Holder of probenecid. However, in case of difficulty in obtaining probenecid the local representative of the Marketing Authorisation Holder of Cidofovir 75 mg/ml Concentrate for Solution for Infusion should be contacted for information (see also sections 4.2 and 4.4).