Cyclophosphamide

Renal Impairment In patients with severe renal impairment, decreased renal excretion may result in increased plasma levels of cyclophosphamide and its metabolites, which may increase toxicity [see Clinical Pharmacology]. Monitor patients with severe renal impairment (creatinine clearance CrCl = 10 mL/min to 24 mL/min) for signs and symptoms of toxicity.

Cyclophosphamide and its metabolites are dialyzable although there are probably quantitative differences depending upon the dialysis system. In patients requiring dialysis, consider using a consistent interval between cyclophosphamide administration and dialysis.

Hepatic Impairment Patients with severe hepatic impairment have reduced conversion of cyclophosphamide to the active 4-hydroxyl metabolite, potentially reducing efficacy [see Clinical Pharmacology]. Monitor patients with severe hepatic impairment (total bilirubin > 3 x ULN and any aspartate aminotransferase (AST)) for reduced effectiveness of cyclophosphamide.

The alcohol content of Cyclophosphamide Injection should be taken into account when given to patients with hepatic impairment [see Warnings and Precautions].

Important Administrative Instructions During or immediately after the administration of Cyclophosphamide Injection, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, Cyclophosphamide Injection should be administered in the morning.

Preparation, Handling, and Administration Cyclophosphamide Injection is a hazardous drug. Follow applicable special handling and disposal procedures 1 Caution should be exercised when handling and preparing Cyclophosphamide Injection. To minimize the risk of dermal exposure, always wear gloves when handling vials containing Cyclophosphamide Injection.

Cyclophosphamide Injection Intravenous Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Cyclophosphamide does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions.

Use aseptic technique. For Direct Intravenous Injection Aseptically withdraw the prescribed dose from the vial. Dilute the prescribed dose of Cyclophosphamide Injection to a concentration of 20 mg per mL by using any of the following diluents: 0.9% Sodium Chloride Injection, USP 0.45% Sodium Chloride Injection, USP 5% Dextrose Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP For Intravenous Infusion Aseptically withdraw the prescribed dose from the vial.

Dilute the prescribed dose of Cyclophosphamide Injection to a concentration of 2 mg per mL by using any of the following diluents: 0.9% Sodium Chloride Injection, USP 0.45% Sodium Chloride Injection, USP 5% Dextrose Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP To reduce the likelihood of adverse reactions that appear to be administration rate-dependent (e.g., facial swelling, headache, nasal congestion, scalp burning), Cyclophosphamide Injection should be injected or infused very slowly.

Duration of the infusion also should be appropriate for the volume and type of carrier fluid to be infused. Storage of Diluted Cyclophosphamide Solution: If not used immediately, for microbiological integrity, cyclophosphamide solutions should be stored as described in Table 1 : [See table below.] 0.45% Sodium Chloride Injection, USP Up to 24 hours Up to 6 days 5% Dextrose Injection, USP Up to 24 hours Up to 6 days 5% Dextrose and 0.9% Sodium chloride Injection, USP Up to 24 hours Up to 6 days Diluted solutions (2 mg/mL) 0.9% Sodium Chloride Injection, USP Up to 24 hours Up to 6 days 0.45% Sodium Chloride Injection, USP Up to 24 hours Up to 6 days 5% Dextrose Injection, USP Up to 24 hours Up to 6 days 5% Dextrose and 0.9% Sodium chloride Injection, USP Up to 24 hours Up to 6 days Storage of Undiluted Cyclophosphamide Solution: After first use, store partially used multiple-dose vial in the original carton at 2°C to 8°C (36°F to 46°F) for up to 28 days.

Discard unused portion after 28 days.