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Cytoxan (Lyophilized) (cyclophosphamide)
Cyclophosphamide cross-links tumor cell DNA and interferes with malignant cell growth through active alkylating metabolites.
Cyclophosphamide is an alkylating agent indicated for treatment of malignant lymphomas, leukemias, solid tumors, and minimal change nephrotic syndrome in pediatric patients. The drug demonstrates linear pharmacokinetics over approved dose ranges with a 3-12 hour half-life and undergoes hepatic and renal elimination. Significant risks include myelosuppression, hemorrhagic cystitis, cardiotoxicity, pulmonary toxicity, hepatotoxicity, and secondary malignancies; contraindicated in patients with urinary outflow obstruction or severe hypersensitivity. Multiple drug interactions require monitoring, particularly with protease inhibitors, radiation therapy, and anticoagulants.
At a glance
| Generic name | cyclophosphamide |
|---|---|
| Sponsor | Baxter |
| Drug class | Alkylating agent |
| Target | Tumor cell DNA |
| Therapeutic area | Oncology |
| Phase | FDA-approved |
| First approval | 1959 |
| Annual revenue | 1000 |
Mechanism of action
Cyclophosphamide is a prodrug that requires metabolic activation to exert its cytotoxic effects. The mechanism of action has not been fully characterized, but cross-linking of tumor cell DNA appears to be involved. The active alkylating metabolites of cyclophosphamide interfere with the growth of susceptible rapidly proliferating malignant cells. Cyclophosphamide is metabolized by cytochrome P450 enzymes (CYP2A6, 2B6, 3A, 2C9, and 2C19) to form 4-hydroxycyclophosphamide, which equilibrates with its ring-open tautomer aldophosphamide. These intermediates can undergo β-elimination to form active metabolites phosphoramide mustard and acrolein, which are responsible for the alkylating activity. The drug demonstrates auto-induction of its own metabolism, resulting in increased clearance and shortened half-life following multiple doses at 12-to 24-hour intervals. At high doses, the fraction of parent compound cleared by 4-hydroxylation is reduced, resulting in non-linear elimination kinetics.
Approved indications
- Acute lymphoid leukemia, disease
- Acute monocytic leukemia
- Acute myelogenous leukemia
- Adenocarcinoma of the ovary
- Burkitt's lymphoma
- Carcinoma of breast
- Chronic lymphoid leukemia, disease
- Chronic myeloid leukemia
- Histiocytic lymphoma
- Hodgkin's disease
- Malignant lymphoma
- Mixedcell type lymphoma
- Multiple myeloma
- Mycosis fungoides
- Neuroblastoma
- Retinoblastoma
- Systemic AL amyloidosis
- Treatment prior to tumor-specific T-cell infusion therapy
Common side effects
- DIARRHOEA
- NAUSEA
- ALOPECIA
- FATIGUE
- VOMITING
- ARTHRALGIA
- Fatigue
- ANAEMIA
- Nausea
- CONSTIPATION
- STOMATITIS
- RASH
Drug interactions
- Protease inhibitors
- Radiation therapy or drugs causing myelosuppression, immunosuppression, nephrotoxicity, cardiotoxicity, pulmonary toxicity, secondary malignancies, or hepatotoxicity
- Metronidazole
- Tamoxifen
- Warfarin and other coumarins
- Cyclosporine
Patents
| Patent | Expiry | Type |
|---|---|---|
| 12329767 | 2036-02-15 | Formulation |
| 10993952 | 2036-02-15 | Formulation |
| 9662342 | 2035-06-26 | Formulation |
| 10849916 | 2035-07-13 | Formulation |
| 11382923 | 2035-12-01 | Formulation |
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| FDA Orange Book | Patents + exclusivity |
| SEC EDGAR | Revenue + earnings |