Ifosfamide information from DrugsUpdate  

Pharmacodynamics

Pharmacokinetics

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.

Absorption Well absorbed from the GI tract (oral).

Metabolism It is a prodrug that is extensively hepatically metabolised to a mixture of active and inactive metabolites.

Excretion Urine (as unchanged drug and metabolites).

Ifosfamide Indications / Ifosfamide Uses

Information Not Available

Ifosfamide Adverse Reactions / Ifosfamide Side Effects

Confusion, alopoecia, nausea, vomiting, phloebitis, somnolence, depression, hallucinations. Wound healing may be impaired during ifosfamide use. Potentially Fatal: Severe myelosuppression, haemorrhagic cystitis, nephrotoxicity, cardiotoxicity, coma.

Precautions

Ifosfamide should be given cautiously to patients with impaired renal function as well as to those with compromised bone marrow reserve, as indicated by: leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents.

Special Precautions

Hepatic or renal dysfunction, compromised bone marrow reserve. Use with mesna and ensure high oral/IV fluid intake to reduce urotoxic effects.

Other Drug 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.

Other Interactions

Food Interaction St John's wort may reduce its serum levels.

Dosage

Intravenous Solid tumours of cervix, lungs, thymus, testes and ovary 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. CrCl (ml/min): <10 Dosage Recommendation: Administer 75% of dose. Intravenous Lymphoma 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. CrCl (ml/min): <10 Dosage Recommendation: Administer 75% of dose. Intravenous Sarcoma 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. CrCl (ml/min): <10 Dosage Recommendation: Administer 75% of 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. CrCl (ml/min): <10 Dosage Recommendation: Administer 75% of dose. 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. Incompatibility Y-site admin: Cefepime, methotrexate. Admixture or in syringe: Mesna with epirubicin.

Food(before/after)

Information Not Available

Ifosfamide and Pregnancy

Contraindicated in pregnancy Contraindicated in 1st trimester: Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Ifosfamide and Lactation

Contraindicated in lactation

Ifosfamide and Children

Safety and efficacy not established

Ifosfamide and Geriatic

Information Not Available

Ifosfamide and Other Contraindications

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

Storage

Intravenous Store at 20-25 ℃

Lab interference

Intravenous Store at 20-25 ℃