The total leukocyte count is a good, objective guide for regulating dosage. T ransient decreases in the total white blood cell count to 2000 cells/mm 3 (following short courses) or more persistent reduction to 3000 cells/ mm3 (with continuing therapy) are tolerated without serious risk of infection if there is no marked granulocytopenia. When cyclophosphamide is included in combined cytotoxic regimens, it may be necessary to reduce the dose of cyclophosphamide aswell as that of the other drugs.Cyclophosphamide and its metabolites are dialyzable although there are probably quantitative differences depending upon the dia lysis system being used. Patients with compromised renal function may show some measurable changes in pharmacokinetic parameters ofcyclophosphamide metabolism, but there is no consistent evidence indicating a need for cyclophosphamide dosage modification inpatients with renal function impairment. Treatment of Nonmalignant Diseases Biopsy Proven “Minimal Change’’ Nephrotic Syndrome in Children An oral dose of 2.5 to 3 mg/kg daily for a period of 60 to 90 days is recommended. In males, the incidence of oligospermia and azoospermia increases if the duration of cyclophosphamide treatment exceeds 60 days. Treatment beyond 90 days increases theprobability of sterility. Adrenocorticosteroid therapy may be tapered and discontinued during the course of cyclophosphamide th erapy. See PRECAUTIONS section concerning hematologic monitoring. Preparation and Handling of Solutions Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, wheneve r solution and container permit. Cyclophosphamide should be prepared for parenteral use by adding 0.9% sterile sodium chloride solution if injected directly.Cyclophosphamide should be prepared for parenteral use by infusion by adding Sterile Water for Injection, USP. Cyclophosphamide,constituted in water, is hypotonic and should not be injected directly. Add the diluent to the vial and shake it vigorously to dissolve. If the powder fails to dissolve immediately and completely, it is advisable to allow the vial to stand for a few minutes. Use the quantity of diluent shown below to constitute the product: Dosage Strength Cyclophosphamide for Injection Contains Cyclophosphamide MonohydrateQuantity of Diluent 500 mg 534.5 mg 25 mL 1 g 1069.0 mg 50 mL 2 g 2138.0 mg 100 mL Solutions of cyclophosphamide may be injected intravenously, intramuscularly, intraperitoneally, or intrapleurally if constitut ed by adding 0.9% sodium chloride solution, or they may be infused intravenously in the following:Dextrose Injection, USP (5% dextrose)Dextrose and Sodium Chloride Injection, USP (5% dextrose and 0.9% sodium chloride)5% Dextrose and Ringer’s InjectionLactated Ringer’s Injection, USPSodium Chloride Injection, USP (0.45% sodium chloride)Sodium Lactate Injection, USP (1/6 molar sodium lactate)Constituted cyclophosphamide is chemically and physically stable for 24 hours at room temperature or for six days in the refrigerator;it does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions.The osmolarities of solutions of cyclophosphamide constituted with water and 0.9% sodium chloride solution are found in thefollowing table:Protocol ADU-CL-02-v8Aduro Biotech, Inc. CRS-207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 127 page 6 of 9Cyclophosphamide and Diluent mOsm/L 5 mL water per 100 mg cyclophosphamide (anhydrous) 74 5 mL 0.9% sodium chloride solution per 100 mg cyclophosphamide (anhydrous) 374 Isotonic 0.9% sodium chloride solution has an osmolarity of 289 mOsm/L. Cyclophosphamide solution in water is hypotonic.Extemporaneous liquid preparations of cyclophosphamide for oral administration may be prepared by dissolving cyclophosphamide i n Aromatic Elixir, N.F.& Such preparations should be stored under refrigeration in glass containers and used within 14 days. HOW SUPPLIED Cyclophosphamide for Injection, USP contains cyclophosphamide monohydrate and is supplied in vials for single dose use. NDC 10019-955-01 500 mg vial, carton of 1NDC 10019-956-01 1.0 g vial, carton of 1NDC 10019-957-01 2.0 g vial, carton of 1Store vials at or below 25°C (77°F) [see USP Controlled Room Temperature]. During transport or storage of cyclophosphamidevials, temperature influences can lead to melting of the active ingredient, cyclophosphamide. Vials containing melted substance canbe visually differentiated. Melted cyclophosphamide is a clear or yellowish viscous liquid usually found as a connected phase or indroplets in the affected vials. Do not use cyclophosphamide vials if there are signs of melting.Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have b een published.