Ifosfamide is given quickly, and in some cases can be given as quickly as an hour.
Mechanism of action
Ifosfamide is a DNA-damaging alkylating agent, belonging to the same class of chemotherapy drugs as cyclophosphamide. It is a prodrug, meaning that It has to be converted by CYP450 into its main active metabolites-(Iso)phosphoramide mustards. These metabolites form DNA cross links mainly at Guanine N-7 positions.[5]
Side effects
Hemorrhagic cystitis is rare when ifosfamide is given with mesna. A common and dose-limiting side effect is encephalopathy (brain dysfunction).[6] It occurs in some form in up to 50% of people receiving the agent. The reaction is probably mediated by chloroacetaldehyde, one of the breakdown products of the ifosfamide molecule, which has chemical properties similar to acetaldehyde and chloral hydrate. The symptoms of ifosfamide encephalopathy can range from mild (difficulty concentrating, fatigue), to moderate (delirium, psychosis), to severe (nonconvulsive status epilepticus or coma). In children, this can interfere with neurological development. Apart from the brain, ifosfamide can also affect peripheral nerves. The severity of the reaction can be classified according to either the National Cancer Institute or the Meanwell criteria (grade I–IV). Previous brain problems and low levels of albumin in the blood increase the likelihood of ifosfamide encephalopathy. In most cases, the reaction resolves spontaneously within 72 hours. If it develops during an infusion of the drug, discontinuing the infusion is advised. The most effective treatment for severe (grade III–IV) encephalopathy is an intravenous solution of methylene blue, which appears to shorten the duration of encephalopathy; the exact mechanism of action of methylene blue is unclear. In some cases, methylene blue may be used as a prophylaxis before further doses of ifosfamide are administered. Other treatments include albumin and thiamine, and dialysis as a rescue modality.[6]
↑World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
↑Colvin ME, Sasaki JC, Tran NL (August 1999). "Chemical factors in the action of phosphoramidic mustard alkylating anticancer drugs: roles for computational chemistry". Current Pharmaceutical Design. 5 (8): 645–663. doi:10.2174/1381612805666230110215849. PMID10469896.
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