DOSAGE AND ADMINISTRATION
Adults and Children
When used as the only oncolytic drug therapy, the initial course of CYTOXAN for patients with no hematologic deficiency usually consists of 40 to 50 mg/kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 to 15 mg/kg given every 7 to 10 days or 3 to 5 mg/kg twice weekly.
Oral CYTOXAN dosing is usually in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Many other regimens of intravenous and oral CYTOXAN have been reported. Dosages must be adjusted in accord with evidence of antitumor activity and/or leukopenia. The total leukocyte count is a good, objective guide for regulating dosage. Transient decreases in the total white blood cell count to 2000 cells/mm3 (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 CYTOXAN is included in combined cytotoxic regimens, it may be necessary to reduce the dose of CYTOXAN as well as that of the other drugs.
CYTOXAN and its metabolites are dialyzable although there are probably quantitative differences depending upon the dialysis system being used. Patients with compromised renal function may show some measurable changes in pharmacokinetic parameters of CYTOXAN metabolism, but there is no consistent evidence indicating a need for CYTOXAN dosage modification in patients with renal function impairment.
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 CYTOXAN treatment exceeds 60 days. Treatment beyond 90 days increases the probability of sterility. Adrenocorticosteroid therapy may be tapered and discontinued during the course of CYTOXAN therapy. See PRECAUTIONS concerning hematologic monitoring.
Preparation and Handling of Solutions
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
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 | CYTOXAN
Contains
Cyclophosphamide
Monohydrate | Quantity of Diluent |
| 500 mg | 534.5 mg | 25 mL |
| 1 g | 1069.0 mg | 50 mL |
| 2 g | 2138.0 mg | 100 mL |
For Direct Injection
CYTOXAN should be prepared for parenteral use by adding 0.9% sterile sodium chloride solution. Solutions of CYTOXAN may be injected intravenously, intramuscularly, intraperitoneally, or intrapleurally if constituted by adding 0.9% sterile sodium chloride solution.
For Infusion
CYTOXAN may be prepared for parenteral use by infusion using any of the following methods:
- CYTOXAN constituted with 0.9% sterile sodium chloride may be infused without further dilution.
- CYTOXAN constituted with 0.9% sterile sodium chloride may be infused following further dilution in the following:
Dextrose Injection, USP (5% dextrose)
Dextrose and Sodium Chloride Injection, USP (5% dextrose and 0.9% sterile sodium chloride)
5% Dextrose and Ringer’s Injection
Lactated Ringer’s Injection, USP
Sodium Chloride Injection, USP (0.45% sterile sodium chloride)
Sodium Lactate Injection, USP (1/6 molar sodium lactate)
- CYTOXAN sterile powder may be prepared for parenteral use by infusion by adding Sterile Water for Injection, USP. CYTOXAN, constituted in water, is hypotonic and should not be injected directly. Prior to infusion, solutions of sterile powder constituted in Sterile Water for Injection, USP must be further diluted in one of the following:
Dextrose Injection, USP (5% dextrose)
Dextrose and Sodium Chloride Injection, USP (5% dextrose and 0.9% sterile sodium chloride)
5% Dextrose and Ringer’s Injection
Lactated Ringer’s Injection, USP
Sodium Chloride Injection, USP (0.45% sterile sodium chloride)
Sodium Lactate Injection, USP (1/6 molar sodium lactate)
Stability of Constituted Parenteral Solutions
CYTOXAN (prepared for either direct injection or infusion) 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 CYTOXAN constituted with water and 0.9% sterile sodium chloride solution are found in the following table:
| CYTOXAN and Diluent | mOsm/L |
| 5 mL water per 100 mg cyclophosphamide (anhydrous) | 74 |
| 5 mL 0.9% sterile sodium chloride solution per 100 mg cyclophosphamide (anhydrous) | 374 |
Isotonic 0.9% sterile sodium chloride solution has an osmolarity of 289 mOsm/L.
For Oral Administration
Extemporaneous liquid preparations of CYTOXAN for oral administration may be prepared by dissolving CYTOXAN in Aromatic Elixir, N.F. Such preparations should be stored under refrigeration in glass containers and used within 14 days.
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