Drug information of Ifosfamide
Mechanism of effect
Ifosfamide is a prodrug. its cytotoxic action is primarily through DNA crosslinks caused by alkylation by the isophosphoramide mustard at guanine N-7 positions. The formation of inter- and intra-strand cross-links in the DNA results in cell death.
Ifosfamide requires activation by microsomal liver enzymes to active metabolites in order to exert its cytotoxic effects
Metabolism: Primarily hepatic. Ifosfamide is extensively metabolized in humans. After administration of doses of 5 g/m2 of 14C-labeled ifosfamide, from 70% to 86% of the dosed radioactivity was recovered in the urine, with about 61% of the dose excreted as parent compound. At doses of 1.6–2.4 g/m2 only 12% to 18% of the dose was excreted in the urine as unchanged drug within 72 hours. Half life: 7-15 hours.
Usual Adult Dose for Testicular Cancer
For third line chemotherapy of germ cell testicular cancer:
1.2 g/m2, diluted to 50 mg/mL IV over 30 minutes once a day with mesna (intravenous, oral, or continuous intravenous infusion) just before and 4 and 8 hours after each dose and aggressive (usually IV) hydration (2 to 4 L/day).
Ifosfamide is usually given for 5 days, with 5 day regimens repeated every 3 to 4 weeks, and after recovery from hematologic toxicity.
Side effectsnausea , Dermatit , Hematuria , vomiting , fatigue , rash , Diarrhea , hypotension , thrombocytopenia , leukopenia , anemia , Alopecia , Infections , anorexia , malaise , renal failure
InteractionsAprepitant , Erythromycin , Itraconazole , Imatinib , Bosentan , Posaconazole , pimecrolimus , Clozapine , denosumab , Nilotinib , Warfarin , Verapamil , Voriconazole , Ketoconazole , Clarithromycin , Diltiazem , Fluconazole , Phenobarbital , Phenytoin , Phenytoin phenobarbital , Natalizumab , Trastuzumab , Tranylcypromine , Melatonin , Vitamin A , teriflunomide , Meglumine Compound , Varicella-Zoster Vaccines , thiotepa , brigatinib , Adenovirus types 4 and 7 live, oral , Diatrizoate (Amidotrizoic acid) , Isavuconazonium , Baricitinib , Ioxaglate , Iothalamate Meglumine , nivolumab , Cannabidiol , Meningococcal conjugate vaccine , Rabies Vaccine , Oprelvekin
1-Myelosuppression can be severe and lead to fatal infections. Monitor blood counts prior to and at intervals after each treatment cycle.
2-CNS toxicities can be severe and result in encephalopathy and death. Monitor for CNS toxicity and discontinue treatment for encephalopathy.
3-Nephrotoxicity can be severe and result in renal failure. Hemorrhagic cystitis can be severe and can be reduced by the prophylactic use of mesna.
Points of recommendation
1-Use with caution in patients with renal or hepatic impairment.
2-Unless clinically essential, initial or repeat doses should not be given to patients with a white blood cell count less than 1500 to 2000/mm3 and/or a platelet count less than 50,000/mm3.
3-Ifosfamide should be discontinued if neurologic symptoms of somnolence, irritability, anxiety, confusion, hallucinations, or coma are observed.