Info

🌱 來自: cyclophosphamide

endoxan

• Dosing: 1-5 mg/kg/d PO OR 75-100 mg/m2/d PO × 14 d every 4 wks OR 250-1,800 mg/m2/dose IV × 1-4 d every 3-4 wks OR 40-50 mg/kg IV divided over 2-5 d OR 50-60 mg/kg/d IV × 2-4 doses prior to HSCT. Consider dose adjustment w/ renal & hepatic impairments
• PK/PD: PO bioavailability >75%; prodrug hepatically activated via CYP2B6, 3A4, & 2C9 (metabolites reduce glutathione); renal excretion, T1/2 3-12 h
• AEs: Myelosuppression (DLT; recovery: 7-10 d), hemorrhagic cystitis, nephrotoxicity, SIADH, N/V (high [>1,500 mg/m2], mod. [≤1,500 mg/m2 or PO] emetogenic risk), cardiotoxicity, alopecia, sterility, 2° malignancies
• DDI: CYP3A4 inducers (phenobarbital, phenytoin, carbamazepine; ↑ cyclophosphamide metabolism to active metabolites), CYP3A4 inhibitors (aprepitant, azole antifungals; ↓ cyclophosphamide metabolism)
• Clinical pearls: Properly hydrate pt pre/post-tx. Hemorrhagic cystitis due to accumulation of acrolein in the bladder, can be prevented w/ MESNA (cumulative dose 60-100% of cyclophosphamide dose)