Cidofovir

Creatinine clearance for females = -------------------------------------------------------------- 72 × [serum creatinine (mg/dL)] Maintenance Treatment The recommended maintenance dose of cidofovir injection is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr), administered once every 2 weeks.

Dose Adjustment Changes in Renal Function During cidofovir injection Therapy The maintenance dose of cidofovir injection must be reduced from 5 mg/kg to 3 mg/kg for an increase in serum creatinine of 0.3 to 0.4 mg/dL above baseline. Cidofovir injection therapy must be discontinued for an increase in serum creatinine of ≥0.5 mg/dL above baseline or development of ≥3+ proteinuria.

Preexisting Renal Impairment Cidofovir injection is contraindicated in patients with a serum creatinine concentration >1.5 mg/dL, a calculated creatinine clearance ≤55 mL/ min, or a urine protein ≥100 mg/dL (equivalent to ≥2+ proteinuria). Probenecid Probenecid must be administered orally with each cidofovir injection dose.

Two grams must be administered 3 hr prior to the cidofovir injection dose and one gram administered at 2 and again at 8 hr after completion of the 1 hr cidofovir infusion (for a total of 4 grams).Ingestion of food prior to each dose of probenecid may reduce drug-related nausea and vomiting. Administration of an antiemetic may reduce the potential for nausea associated with probenecid ingestion.

In patients who develop allergic or hypersensitivity symptoms to probenecid, the use of an appropriate prophylactic or therapeutic antihistamine and/or acetaminophen should be considered (see CONTRAINDICATIONS ). Hydration Patients must receive at least one liter of 0.9% (normal) saline solution intravenously with each infusion of cidofovir injection.

The saline solution should be infused over a 1 to 2 hr period immediately before the cidofovir infusion. Patients who can tolerate the additional fluid load should receive a second liter. If administered, the second liter of saline should be initiated either at the start of the cidofovir infusion or immediately afterwards, and infused over a 1 to 3 hr period.

Method of Preparation and Administration Inspect vials visually for particulate matter and discoloration prior to administration. If particulate matter or discoloration is observed, the vial should not be used. With a syringe, extract the appropriate volume of cidofovir injection from the vial and transfer the dose to an infusion bag containing 100 mL 0.9% (normal) saline solution.

Infuse the entire volume intravenously into the patient at a constant rate over a 1 hr period. Use of a standard infusion pump for administration is recommended. It is recommended that cidofovir infusion admixtures be administered within 24 hr of preparation and that refrigerator or freezer storage not be used to extend this 24 hr limit.If admixtures are not intended for immediate use, they may be stored under refrigeration (2 to 8°C) for no more than 24 hr.

Refrigerated admixtures should be allowed to equilibrate to room temperature prior to use. The chemical stability of cidofovir injection admixtures was demonstrated in polyvinyl chloride composition and ethylene/propylene copolymer composition commercial infusion bags, and in glass bottles. No data are available to support the addition of other drugs or supplements to the cidofovir admixture for concurrent administration.

Cidofovir injection is supplied in single-dose vials. Partially used vials should be discarded (see Handling and Disposal). Compatibility with Ringer's solution, Lactated Ringer's solution or bacteriostatic infusion fluids has not been evaluated. Handling and Disposal Due to the mutagenic properties of cidofovir, adequate precautions including the use of appropriate safety equipment are recommended for the preparation, administration, and disposal of cidofovir injection.

The National Institutes of Health presently recommends that such agents be prepared in a Class II laminar flow biological safety cabinet and that personnel preparing drugs of this class wear surgical gloves and a closed front surgical-type gown with knit cuffs. If cidofovir injection contacts the skin, wash membranes and flush thoroughly with water.

Excess cidofovir injection and all other materials used in the admixture preparation and administration should be placed in a leak-proof, puncture-proof container. The recommended method of disposal is high temperature incineration. Patient Monitoring Serum creatinine and urine protein must be monitored within 48 hours prior to each dose.

White blood cell counts with differential should be monitored prior to each dose. In patients with proteinuria, intravenous hydration should be administered and the test repeated. Intraocular pressure, visual acuity and ocular symptoms should be monitored periodically.

DOSAGE AND ADMINISTRATION CIDOFOVIR INJECTION, USP MUST NOT BE ADMINISTERED BY INTRAOCULAR INJECTION. Dosage THE RECOMMENDED DOSAGE, FREQUENCY, OR INFUSION RATE MUST NOT BE EXCEEDED. CIDOFOVIR INJECTION, USP MUST BE DILUTED IN 100 MILLILITERS 0.9% (NORMAL) SALINE PRIOR TO ADMINISTRATION. TO MINIMIZE POTENTIAL NEPHROTOXICITY, PROBENECID AND INTRAVENOUS SALINE PREHYDRATION MUST BE ADMINISTERED WITH EACH CIDOFOVIR INFUSION.

Two grams must be administered 3 hr prior to the cidofovir injection dose and one gram administered at 2 and again at 8 hr after completion of the 1 hr cidofovir infusion (for a total of 4 grams).Ingestion of food prior to each dose of probenecid may reduce drug-related nausea and vomiting. Administration of an antiemetic may reduce the potential for nausea associated with probenecid ingestion.

In patients who develop allergic or hypersensitivity symptoms to probenecid, the use of an appropriate prophylactic or therapeutic antihistamine and/or acetaminophen should be considered (see CONTRAINDICATIONS ). Hydration Patients must receive at least one liter of 0.9% (normal) saline solution intravenously with each infusion of cidofovir injection.

The saline solution should be infused over a 1 to 2 hr period immediately before the cidofovir infusion. Patients who can tolerate the additional fluid load should receive a second liter. If administered, the second liter of saline should be initiated either at the start of the cidofovir infusion or immediately afterwards, and infused over a 1 to 3 hr period.

Method of Preparation and Administration Inspect vials visually for particulate matter and discoloration prior to administration. If particulate matter or discoloration is observed, the vial should not be used. With a syringe, extract the appropriate volume of cidofovir injection from the vial and transfer the dose to an infusion bag containing 100 mL 0.9% (normal) saline solution.

Infuse the entire volume intravenously into the patient at a constant rate over a 1 hr period. Use of a standard infusion pump for administration is recommended. It is recommended that cidofovir infusion admixtures be administered within 24 hr of preparation and that refrigerator or freezer storage not be used to extend this 24 hr limit.If admixtures are not intended for immediate use, they may be stored under refrigeration (2 to 8°C) for no more than 24 hr.

Refrigerated admixtures should be allowed to equilibrate to room temperature prior to use. The chemical stability of cidofovir injection admixtures was demonstrated in polyvinyl chloride composition and ethylene/propylene copolymer composition commercial infusion bags, and in glass bottles. No data are available to support the addition of other drugs or supplements to the cidofovir admixture for concurrent administration.

Cidofovir injection is supplied in single-dose vials. Partially used vials should be discarded (see Handling and Disposal). Compatibility with Ringer's solution, Lactated Ringer's solution or bacteriostatic infusion fluids has not been evaluated. Handling and Disposal Due to the mutagenic properties of cidofovir, adequate precautions including the use of appropriate safety equipment are recommended for the preparation, administration, and disposal of cidofovir injection.

Excess cidofovir injection and all other materials used in the admixture preparation and administration should be placed in a leak-proof, puncture-proof container. The recommended method of disposal is high temperature incineration. Patient Monitoring Serum creatinine and urine protein must be monitored within 48 hours prior to each dose.