Ifosfamide

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Ifosfamide
Ifosfamide.svg
Ifosfamide-3D-balls.png
Systematic (IUPAC) name
N-3-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amide-2-oxide
Clinical data
Trade names Ifex
AHFS/Drugs.com monograph
MedlinePlus a695023
Pregnancy cat.
Legal status
  • Prescription only
Routes intravenously
Pharmacokinetic data
Bioavailability 100%
Metabolism Hepatic
Half-life 60-80% in 72 hours
Excretion Renal
Identifiers
CAS number 3778-73-2 YesY
ATC code L01AA06
PubChem CID 3690
DrugBank DB01181
ChemSpider 3562 YesY
UNII UM20QQM95Y YesY
KEGG D00343 YesY
ChEBI CHEBI:5864 YesY
ChEMBL CHEMBL1024 YesY
Synonyms 3-(2-chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide
Chemical data
Formula C7H15Cl2N2O2P 
Mol. mass 261.1 g mol−1
 YesY (what is this?)  (verify)

Ifosfamide (also marketed as Ifex) is a nitrogen mustard alkylating agent used in the treatment of cancer.[1]

It is sometimes abbreviated "IFO".[2]

Uses[edit]

It is given as a treatment for a variety of cancers, including:

Administration[edit]

It is a white powder which, when prepared for use in chemotherapy, becomes a clear, colorless fluid. The delivery is intravenous.

Ifosfamide is often used in conjunction with mesna to avoid internal bleeding in the patient, in particular hemorrhagic cystitis.

Ifosfamide is given quickly, and in some cases can be given in as little as an hour.

Toxicity[edit]

Hemorrhagic cystitis is rare when ifosfamide is given together with mesna.

A common and dose-limiting side effect is encephalopathy (brain dysfunction).[3] 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.[3]

Ifosfamide may also cause a normal anion gap acidosis, specifically renal tubular acidosis type 2.[4]

Synthesis[edit]

Ifosfamide synthesis:[5] FR 1530962  U.S. Patent 3,732,340.

References[edit]

  1. ^ Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
  2. ^ Jahnke K, Thiel E, Bechrakis NE, et al. (December 2008). "Ifosfamide or trofosfamide in patients with intraocular lymphoma". J. Neurooncol. 93 (2): 213–7. doi:10.1007/s11060-008-9761-8. PMID 19099202. 
  3. ^ a b Ajithkumar T, Parkinson C, Shamshad F, Murray P (March 2007). "Ifosfamide encephalopathy". Clin Oncol (R Coll Radiol) 19 (2): 108–14. doi:10.1016/j.clon.2006.11.003. PMID 17355105. 
  4. ^ Foster, Corey, ed. (2010). The Washington Manual of Therapeutics (33 ed.). Wolters Kluwer | Lippincott Williams & Wilkins. p. 407. 
  5. ^ Brassfield, H. A.; Jacobson, R. A.; Verkade, J. G. (1975). "Molecular structure of the carcinostat isophosphamide". Journal of the American Chemical Society 97 (14): 4143. doi:10.1021/ja00847a053. PMID 1159218.  edit

External links[edit]