The recommended dose of BiCNU (carmustine) as a single agent in previously untreated patients is 150 to 200 mg/m intravenously every 6 weeks. This may be given as a single dose or divided into daily injections such as 75 to 100 mg/m2 on 2 successive days. When BiCNU (carmustine) is used in combination with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted, the doses should be adjusted accordingly. Doses subsequent to the initial dose should be adjusted according to the hematologic response of the patient to the preceding dose. The following schedule is suggested as a guide to dosage adjustment: Nadir After Prior Dose Percentage of Prior Dose to be Given Leukocytes/mm3 Platelets/mm3 >4000 >100,000 100% 3000-3999 75,000-99,999 100% 2000-2999 25,000-74,999 70% <2000 <25,000 50% A repeat course of BiCNU (carmustine) should not be given until circulating blood elements have returned to acceptable levels (platelets above 100,000/mm3, leukocytes above 4,000/mm3), and this is usually in 6 weeks. Adequate number of neutrophils should be present on a peripheral blood smear. Blood counts should be monitored weekly and repeat courses should not be given before 6 weeks because the hematologic toxicity is delayed and cumulative. Administration Precautions As with other potentially toxic compounds, caution should be exercised in handling BiCNU (carmustine) and preparing the solution of BiCNU (carmustine) . Accidental contact of reconstituted BiCNU (carmustine) with the skin has caused transient hyperpigmentation of the affected areas. The use of gloves is recommended. If BiCNU (carmustine) lyophilized material or solution contacts the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water. The reconstituted solution should be used intravenously only and should be administered by IV drip. Injection of BiCNU (carmustine) over shorter periods of time than 1 to 2 hours may produce intense pain and burning at the site of injection. Preparation of Intravenous Solutions First, dissolve BiCNU (carmustine) with 3 mL of the supplied sterile diluent (Dehydrated Alcohol Injection, USP). Second, aseptically add 27 mL Sterile Water for Injection, USP. Each mL of resulting solution contains 3.3 mg of BiCNU (carmustine) in 10% ethanol. Such solutions should be protected from light. Reconstitution as recommended results in a clear, colorless to yellowish solution which may be further diluted with 5% Dextrose Injection, USP. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Important Note The lyophilized dosage formulation contains no preservatives and is not intended for use as a multiple dose vial. Stability The unopened vial of the dry drug must be stored in a refrigerator (2°-8°C, 36°-46°F). The diluent ampules may be stored at controlled room temperature (59°-86°F, 15°-30°C) or in a refrigerator (2°-8°C, 36°-46°F). The recommended storage of unopened BiCNU (carmustine) vials provides a stable product for up to 3 years. After reconstitution as recommended, BiCNU (carmustine) is stable for 24 hours under refrigeration (2°-8°C, 36°-46°F). Reconstituted vials should be examined for crystal formation prior to use. If crystals are observed, they may be redissolved by warming the vial to room temperature with agitation. Vials reconstituted as directed and further diluted to a concentration of 0.2 mg/mL in 5% Dextrose Injection, USP, should be stored at room temperature, protected from light and utilized within 8 hours. Glass containers were used for the stability data provided in this section. Only use glass containers for BiCNU (carmustine) administration. Important Note BiCNU (carmustine) has a low melting point (30.5°-32.0°C or 86.9°-89.6°F). Exposure of the drug to this temperature or above will cause the drug to liquefy and appear as an oil film on the vials. This is a sign of decomposition and vials should be discarded. If there is a question of adequate refrigeration upon receipt of this product, immediately inspect the vial in each individual carton. Hold the vial to a bright light for inspection. The BiCNU (carmustine) will appear as a very small amount of dry flakes or dry congealed mass. If this is evident, the BiCNU (carmustine) is suitable for use and should be refrigerated immediately. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published 1-8. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. To minimize the risk of dermal exposure, always wear impervious gloves when handling vials containing BiCNU (carmustine) . This includes all handling activities in clinical settings, pharmacies, storerooms, and home healthcare settings, including during unpacking and inspection, transport within a facility, and dose preparation and administration.