Cyclophosphamide

# Cyclophosphamide ## Overview - **Classification**: Alkylating agent, nitrogen mustard derivative, antineoplastic, immunosuppressant. - **Mechanism**: Metabolized to active compounds that cross-link DNA strands, inhibiting DNA synthesis and cell replication, leading to cell death. ## Primary Indications 1. **Malignancies**: Lymphomas, leukemias, multiple myeloma, breast cancer, ovarian cancer. 2. **Autoimmune Diseases**: Severe rheumatoid arthritis, lupus nephritis, granulomatosis with polyangiitis. 3. **Conditioning Regimens**: Bone marrow and stem cell transplantation. ## Adult Dosing ### Standard Dosing **Malignancies (e.g., Lymphoma, Leukemia)** - **Dose**: **500-1500 mg/m² IV** - **Frequency**: Every **2-4 weeks** (varies by regimen) - **Route**: Intravenous (IV) **Immunosuppression (e.g., Lupus Nephritis)** - **Dose**: **0.5-1 g/m² IV** or **10-15 mg/kg IV** - **Frequency**: Every **3-4 weeks** - **Route**: Intravenous (IV) - **Maintenance (Oral)**: **1-2 mg/kg/day PO** (max **200 mg/day**) **Bone Marrow Transplant Conditioning** - **Dose**: **50 mg/kg/day IV** - **Frequency**: Once daily for **2-4 days** - **Route**: Intravenous (IV) - **Maximum**: Total **200 mg/kg** over 4 days ### Dose Adjustments - **Renal Impairment**: - CrCl 25-50 mL/min: Reduce dose by **25%**. - CrCl <25 mL/min: Reduce dose by **50%**. - Hemodialysis: Administer after dialysis. - **Hepatic Impairment**: - Bilirubin >3 mg/dL or AST >3x ULN: Reduce dose by **25%**. - **Elderly Patients**: Monitor closely for myelosuppression and cardiac toxicity. Consider lower starting doses. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: **5-10 mg/kg/dose IV** (for specific conditions) - **Frequency**: Every **1-2 weeks** (limited data) - **Maximum**: Not well established, individualize. - **Special Notes**: High risk of toxicity; use extreme caution due to reduced clearance. ### Infants (1-12 months) - **Dose**: **10-15 mg/kg/dose IV** (immunosuppression) or **500-1000 mg/m² IV** (oncology) - **Frequency**: Every **3-4 weeks** (immunosuppression) or per oncology protocol. - **Maximum**: **1000 mg/m²** per single dose. ### Children (1-12 years) - **Dose**: **10-15 mg/kg/dose IV** (immunosuppression) or **500-1500 mg/m² IV** (oncology) - **Frequency**: Every **3-4 weeks** (immunosuppression) or per oncology protocol. - **Maximum**: **1500 mg/m²** per single dose (oncology regimens may use higher cumulative doses). ### Adolescents (13-18 years) - **Dose**: Generally follow **adult dosing guidelines** based on BSA or weight. - **Maximum**: **Adult maximum doses** apply. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to cyclophosphamide. - **Absolute**: Severe bone marrow depression (unless for BMT). - **Absolute**: Active serious infections. ### Common Adverse Effects - **Very Common (>10%)**: Nausea, vomiting, alopecia, myelosuppression (leukopenia, neutropenia), hemorrhagic cystitis. - **Common (1-10%)**: Diarrhea, stomatitis, fatigue, amenorrhea, azoospermia. - **Serious but Rare**: Cardiotoxicity (myocarditis, CHF), secondary malignancies (bladder cancer, leukemia), interstitial pneumonitis, SIADH, veno-occlusive disease. ### Key Drug Interactions - **Allopurinol**: May increase myelosuppression. Reduce cyclophosphamide dose. - **CYP2B6 Inducers/Inhibitors**: May alter cyclophosphamide activation/clearance (e.g., phenobarbital, cimetidine). - **Anthracyclines**: Increased risk of cardiotoxicity. Monitor cardiac function closely. - **Warfarin**: May increase or decrease anticoagulant effect. Monitor INR. ## Monitoring & Follow-up - **Before Treatment**: CBC with differential, platelets, LFTs, renal function (Cr, BUN), urinalysis, pregnancy test. - **During Treatment**: - **CBC with differential & platelets**: Weekly initially, then less often per protocol. - **Urinalysis**: Before each dose to check for hematuria. - **Renal/Liver function**: Periodically. - **Clinical Signs**: Monitor for infection (fever), bleeding, cardiac symptoms (dyspnea), signs of hemorrhagic cystitis (dysuria, hematuria). ## Clinical Pearls - 💡 **Hydration is CRITICAL**: Administer with vigorous hydration (e.g., **2-3 L/m²/day**) to prevent hemorrhagic cystitis. - 💡 **Mesna**: Consider with high cyclophosphamide doses (>**1 g/m²**) or risk factors for cystitis. It protects the bladder. - 💡 **Timing of Doses**: Give in the morning to allow adequate hydration/voiding before bedtime. - 💡 **Alopecia**: Warn patients about potential hair loss, which is often reversible. - 💡 **Fertility**: Counsel on significant risk of permanent infertility. Discuss fertility preservation options. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.