Ifosfamide (4 brand names, 1 dosage form, 2 routes)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION, INTRAVENOUS.
Brand Names
- IFEX
- IFEX/MESNEX KIT
- IFOSFAMIDE
- IFOSFAMIDE/MESNA KIT
Boxed Warning
•Myelosuppression can be severe and lead to fatal infections. Monitor blood counts prior to and at intervals after each treatment cycle [see Warnings and Precautions (5.1)]. •Encephalopathy can be severe and may result in death. Monitor for CNS toxicity and discontinue treatment for encephalopathy [see Warnings and Precautions (5.2)]. •Nephrotoxicity can be severe and result in renal failure. Hemorrhagic cystitis can be severe and can be reduced by the prophylactic use of mesna [see Warnings and Precautions (5.3)].
Indications and Usage
IFEX is indicated for use in adults in combination with certain other approved antineoplastic agents for third-line chemotherapy of germ cell testicular cancer.
Contraindications
IFEX is contraindicated in patients with: •Known hypersensitivity to administration of ifosfamide. •Urinary outflow obstruction.
Mechanism of Action
Ifosfamide is a prodrug that requires metabolic activation by hepatic cytochrome P450 isoenzymes to exert its cytotoxic activity. Activation occurs by hydroxylation at the ring carbon atom forming the unstable intermediate 4-hydroxyifosfamide and its ring-opened aldo tautomer, which decomposes to yield the cytotoxic and urotoxic compound acrolein and an alkylating isophosphoramide mustard. The exact mechanism of action of ifosfamide has not been determined, but 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.
Overdosage
No specific antidote for IFEX is known. Patients who receive an overdose should be closely monitored for the development of toxicities. Serious consequences of overdosage include manifestations of dose-dependent toxicities such as CNS toxicity, nephrotoxicity, myelosuppression, and mucositis [see Warnings and Precautions (5)]. Management of overdosage would include general supportive measures to sustain the patient through any period of toxicity that might occur, including appropriate state-of-the-art treatment for any concurrent infection, myelosuppression, or other toxicity. Ifosfamide as well as ifosfamide metabolites are dialyzable. Cystitis prophylaxis with mesna may be helpful in preventing or limiting urotoxic effects with overdose.