🔴 Red Flag (Important) Information — Endoxan (Cyclophosphamide)
Myelosuppression (Bone marrow suppression):
Major dose-limiting toxicity — monitor CBC frequently.
Risk of infection, bleeding, and anaemia.
Delay or reduce dose if WBC <3.5 ×10⁹/L or platelets <100 ×10⁹/L.
Hemorrhagic cystitis:
Serious, potentially life-threatening bladder toxicity.
Ensure adequate hydration and frequent voiding.
Mesna co-administration strongly recommended for prevention.
Stop drug if haematuria develops.
Secondary malignancies:
Long-term risk of bladder cancer, leukaemia, and other malignancies — especially with high cumulative doses or radiotherapy.
Cardiotoxicity and pulmonary toxicity:
Risk increases with high doses, prior anthracyclines, or radiotherapy.
Stop if new dyspnoea, chest pain, or ECG abnormalities develop.
Hepatotoxicity:
Rare but can be severe (veno-occlusive disease, hepatic failure).
Stop drug if jaundice, right upper quadrant pain, or elevated LFTs.
Fertility impairment:
May cause permanent infertility in men and women.
Offer sperm or oocyte preservation prior to therapy.
Pregnancy and breastfeeding:
Contraindicated — teratogenic and mutagenic.
Effective contraception required during and for ≥6 months post-therapy.
🔹 1. Basic Information
Generic name: Cyclophosphamide
Brand name: Endoxan
Drug class: Alkylating agent (nitrogen mustard derivative)
Formulation: Sugar-coated oral tablets
Strength: 50 mg
Mechanism of Action:
Prodrug activated in the liver to phosphoramide mustard → alkylates DNA → cross-links strands → inhibits replication and causes cell death, primarily in rapidly dividing cells.
🔹 2. Indications
Malignant diseases:
Lymphomas (Hodgkin and non-Hodgkin)
Leukaemias (acute and chronic)
Multiple myeloma
Breast, ovarian, and small-cell lung cancer
Sarcomas and neuroblastoma
Non-malignant diseases (immunosuppressive use):
Severe autoimmune diseases (e.g., lupus nephritis, vasculitis) — under specialist supervision.
🔹 3. Dosing & Administration
Typical oral dose: 1–4 tablets (50–200 mg) daily (continuous therapy).
Dose individualized based on disease, BSA, and prior chemotherapy/radiation.
Timing: Take in the morning with plenty of fluids.
Hydration: Maintain ≥2 L/day and empty bladder regularly.
Do not crush or split tablets — cytotoxic handling precautions required.
Mesna may be co-administered for bladder protection.
Renal impairment: Reduce dose if significant renal dysfunction.
Hepatic impairment: Monitor LFTs; reduce dose if elevated enzymes or bilirubin.
🔹 4. Dose Modifications
Haematologic toxicity: Delay or reduce dose based on blood counts.
Renal/hepatic dysfunction: Adjust dose or interval.
Bladder toxicity: Stop drug and evaluate for haematuria or cystitis.
Severe adverse effects (e.g., cardiac, pulmonary, hepatic): Permanently discontinue.
🔹 5. Co-medications
Avoid with:
Aprepitant, busulfan, thiotepa, ciprofloxacin, fluconazole, itraconazole (↓ efficacy).
Allopurinol, azathioprine, cimetidine, disulfiram (↑ toxicity).
Anthracyclines, trastuzumab, amiodarone (↑ cardiac toxicity).
Amphotericin B, indomethacin (↑ nephrotoxicity).
Sorivudine or brivudine (contraindicated).
Mesna: Given to prevent hemorrhagic cystitis.
Alcohol: Avoid — increases nausea/vomiting.
Grapefruit: Avoid — impairs activation of cyclophosphamide.
🔹 6. Contraindications
Hypersensitivity to cyclophosphamide or excipients.
Severe bone marrow suppression.
Active infection or urinary tract infection.
Urinary outflow obstruction.
Pregnancy and breastfeeding.
Recent or live vaccination.
🔹 7. Monitoring Requirements
Baseline and periodic:
CBC with differential
Renal and hepatic function tests
Urinalysis for blood (haematuria)
ECG if cardiac history
Ongoing:
Hydration status
Signs of infection or bleeding
Cumulative dose (for long-term malignancy risk)
🔹 8. Side Effects & Management
| Frequency | Adverse Effect | Management |
|---|---|---|
| Very common (>10%) | Nausea, vomiting, anorexia, alopecia, leukopenia | Antiemetics, supportive care |
| Common (1–10%) | Haemorrhagic cystitis, mucositis, fatigue, diarrhoea | Mesna, hydration, symptomatic care |
| Serious (<5%) | Myelosuppression, sepsis, cardiac toxicity, pulmonary fibrosis, hepatotoxicity | Stop drug, supportive management |
| Long-term | Infertility, secondary malignancy, alopecia | Counseling, monitoring |
🔹 9. Use in Special Populations
Elderly: Increased risk of myelosuppression — monitor closely.
Hepatic impairment: Use cautiously; monitor LFTs.
Renal impairment: Reduce dose; ensure hydration.
Pregnancy/Lactation: Contraindicated.
Paediatrics: Dose per BSA; close toxicity monitoring.
🔹 10. Duration of Use / When to Stop
Continue until:
Disease remission or completion of prescribed regimen, or
Unacceptable toxicity.
Stop if:
Severe myelosuppression or haemorrhagic cystitis.
Hepatic, pulmonary, or cardiac toxicity.
Persistent or recurrent infections.
| Generic Name | Cyclophosphamide |
|---|---|
| Drug Class | Alkylating Agents |
| Cost | |
| Company | |
|---|---|
| Drug Rep | Admin |
| Indications | Breast Cancer, Lung Cancer, Ovarian Cancer |
| Dosage |