Generic Name

Ifosfamide

Precaution

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

Indication

Breast cancer, Lung cancer, Ovarian cancer, Lymphoma, Testicular cancer, Soft tissue sarcoma, Osteogenic sarcoma, Cervical cancer

Contra Indication

Hypersensitivity; severe bone-marrow depression. Pregnancy, lactation.

Dose

N/A

Side Effect

>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.

Pregnancy Category

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.

Interaction

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.

Pregnancy Category Note

Pregnancy Category: D Lactation: excreted in breast milk, do not nurse

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.