Generic Name

Cyclophosphamide

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Classification

FDA Approved Indications

• Various cancers including non-Hodgkin lymphoma, leukemia, breast cancer, ovarian cancer, multiple myeloma, neuroblastoma, and others.
• Autoimmune disorders such as rheumatoid arthritis and vasculitis (off-label use)

Mechanism of Action

Cyclophosphamide is a prodrug that is metabolized in the liver to active metabolites that crosslink DNA strands, leading to apoptosis of rapidly dividing cells, including cancer cells and immune cells.

Dosage and Administration

Adult: Dose varies with indication; typically, 500-1500 mg/m² IV every 2-3 weeks, or as per protocol.

Pediatric: Dosing based on body surface area (mg/m²), generally 100-250 mg/m² IV at intervals; adjusted for specific conditions.

Geriatric: Careful dose adjustment is advised due to decreased renal and hepatic function.

Renal Impairment: Dose reductions may be necessary; monitor renal function.

Hepatic Impairment: Adjust dose as hepatic metabolism is involved; monitor liver function.

Pharmacokinetics

Absorption: Administered IV, not absorbed orally; oral formulations are available.

Distribution: Widely distributed across body tissues; crosses the placental barrier and enters breast milk.

Metabolism: Hepatically metabolized by cytochrome P450 enzymes to active metabolites.

Excretion: Primarily excreted via the urine in active and inactive forms.

Half Life: Approximately 3-12 hours, depending on the metabolite and patient factors.

Contraindications

• Hypersensitivity to cyclophosphamide or other alkylating agents.
• Severe bone marrow suppression.
• Active infections.

Precautions

• Use with caution in patients with renal or hepatic impairment.
• Pregnancy risk Category D; use only if clearly needed; effective contraception during therapy and for 6 months after.

Adverse Reactions - Common

• Bone marrow suppression (neutropenia, thrombocytopenia, anemia) (Common)
• Nausea and vomiting (Common)
• Hair loss (alopecia) (Common)

Adverse Reactions - Serious

• Hemorrhagic cystitis (Serious)
• Secondary malignancies (e.g., leukemia) (Serious)
• Infertility (Serious)
• Infections due to immunosuppression (Serious)

Drug-Drug Interactions

• Other myelosuppressive agents, live vaccines, nephrotoxic drugs, cardiotoxic drugs.

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Report signs of infection, bleeding, or hematuria immediately.
• Use effective contraception; avoid pregnancy during therapy.
• Maintain adequate hydration to reduce bladder toxicity.
• Inform about possible hair loss and gastrointestinal side effects.

Special Considerations

Black Box Warnings:

• Hemorrhagic cystitis; risk increased at higher doses.
• Secondary malignancies, including leukemia.
• Myelosuppression leading to increased risk of infection.

Genetic Factors: Pharmacogenetic variability can influence drug metabolism and toxicity.

Lab Test Interference: May cause transient elevations in liver enzymes, bilirubin, and changes in blood counts.

Overdose Management

Signs/Symptoms: Severe myelosuppression, hemorrhagic cystitis, alopecia, nausea, vomiting.

Treatment: Supportive care, monitor labs, administer leucovorin (if indicated), aggressive hydration, and renal support as needed.

Storage and Handling

Storage: Store unopened vials in a refrigerator (2-8°C).

Stability: Stable until expiration date when stored properly.