Ifosfamide
Indications
Ifosfamide is used for:
Breast cancer, Lung cancer, Ovarian cancer, Lymphoma, Testicular cancer, Soft tissue sarcoma, Osteogenic sarcoma, Cervical cancer
Adult Dose
Intravenous
Germ cell testicular carcinoma
Adult: 1.2 g/m2/day for 5 days via slow infusion over at least 30 minutes, repeat treatment every 3 wk or after recovery from haematological toxicity. To be given with mesna and adequate hydration of at least 2 L of oral or IV fluid per day.
Lymphoma; Sarcoma; Solid tumours
Adult: Different licensed dosage regimens are available. Regimen 1: 8-12 g/m2 divided over 3-5 days, repeat course every 2-4 wk. Regimen 2: 6 g/m2 divided over 5 days, repeat course every 3 wk. Regimen 3: 5-6 g/m2 (max: 10 g), give as a single 24-hr infusion, repeat course every 3-4 wkly.
Child Dose
Safety and efficacy not established
Renal Dose
Renal impairment:
CrCl (ml/min)
<10 Administer 75% of dose.
Administration
IV Administration
Slow IV infusion over 30 min, or continuous infusion over 5 d
Mesna should be administered concomitantly (20% of the ifosfamide dose 15 min before, 4 hr after, & 8 hr after ifosfamide administration)
Adequate hydration (at least 2 L/day) before & for 72 hr after therapy is recommended to minimize risk of hemorrhagic cystitis
Reconstitution: Add 20 ml of sterile water for inj or sterile bacteriostatic water for inj containing benzyl alcohol or parabens for each 1 g of the drug to produce solutions of 50 mg/ml.
Contra Indications
Hypersensitivity; severe bone-marrow depression. Pregnancy, lactation.
Precautions
Hepatic or renal dysfunction, compromised bone marrow reserve. Use with mesna and ensure high oral/IV fluid intake to reduce urotoxic effects.
Lactation: excreted in breast milk, do not nurse
Pregnancy-Lactation
Pregnancy Category: D
Lactation: excreted in breast milk, do not nurse
Interactions
Causes enhanced toxicity with allopurinol, cisplatin. Ifosfamide enhances the anticoagulant effect of warfarin. CYP2A6 inducers (e.g. amobarbital, pentobarbital, phenobarbital, rifampin and secobarbital) may reduce serum levels of ifosfamide while the inhibitors (e.g. isoniazid, methoxsalen and miconazole) may increase its serum levels. CYP3A4 inducers (e.g. aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins) may reduce serum levels of ifosfamide while the inhibitors (e.g. azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid) may increase its serum levels.
Side Effects
Side effects of Ifosfamide :
>10%
Alopecia (83%), Nausea (58%), Vomiting (58%), Leukopenia (50%), Hematuria (46%), Metabolic acidosis (31%), Thrombocytopenia (20%), CNS toxicity (12%), Neurotoxicity (10-20%)
1-10%
Infection (8%), Nephrotoxicity (6%)
Potentially Fatal: Severe myelosuppression, haemorrhagic cystitis, nephrotoxicity, cardiotoxicity, coma.
Mode of Action
Ifosfamide is converted to its active metabolites via hepatic microsomal enzymes. These active metabolites act as alkylating agents, disrupting DNA and protein synthesis of the target cells. It is routinely given with mesna to reduce urothelial toxicity.