Ifosfamide

Ifosfamide
(R)-(+)- and (S)-(−)-ifosfamide (top),
(S)-(−)-ifosfamide (bottom)
Names
Pronunciation/aɪˈfɒsfəmaɪd/
Trade namesIfex, others
Other names3-(2-chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide
IUPAC name
  • N,3-Bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amide 2-oxide
Clinical data
Drug classAlkylating agent
Main usesTesticular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, cervical cancer, ovarian cancer[1]
Side effectsHair loss, vomiting, blood in the urine, infections, kidney problems[1]
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Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
    Routes of
    use    		intravenously
    Defined daily dosenot established[2]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa695023
    Legal
    Legal status
    • AU: S4 (Prescription only)
    • CA: ℞-only
    • NZ: Prescription medicine
    • UK: POM (Prescription only)
    • US: ℞-only
    Pharmacokinetics
    Bioavailability100%
    MetabolismHepatic
    Elimination half-life60–80% in 72 hours
    ExcretionRenal
    Chemical and physical data
    FormulaC7H15Cl2N2O2P
    Molar mass261.08 g·mol−1
    3D model (JSmol)
    SMILES
    • O=P1(OCCCN1CCCl)NCCCl
    InChI
    • InChI=1S/C7H15Cl2N2O2P/c8-2-4-10-14(12)11(6-3-9)5-1-7-13-14/h1-7H2,(H,10,12) checkY
    • Key:HOMGKSMUEGBAAB-UHFFFAOYSA-N checkY

    Ifosfamide (IFO), sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer.[1] This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, cervical cancer, and ovarian cancer.[1] It is administered by injection into a vein.[1]

    Common side effects include hair loss, vomiting, blood in the urine, infections, and kidney problems.[1] Other severe side effects include bone marrow suppression and decreased level of consciousness.[1] Use during pregnancy will likely result in harm to the baby.[1] Ifosfamide is in the alkylating agent and nitrogen mustard family of medications.[1][3] It works by disrupting the duplication of DNA and the creation of RNA.[1]

    Ifosfamide was approved for medical use in the United States in 1987.[1] It is on the World Health Organization's List of Essential Medicines.[4] The wholesale cost in the developing world is about US$7.35–70.70 per 2 gm vial.[5] In the UK this dose costs the NHS about 130.04 pounds.[6]

    Medical uses

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

    Administration

    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 as quickly as an hour.


    Dosage

    The defined daily dose is not established[2]

    Side effects

    Hemorrhagic cystitis is rare when ifosfamide is given with mesna. A common and dose-limiting side effect is encephalopathy (brain dysfunction).[7] 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.[7]

    Ifosfamide may also cause a normal anion gap acidosis, specifically renal tubular acidosis type 2.[8]

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 "Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016.
    2. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 11 July 2020. Retrieved 18 September 2020.
    3. ↑ Dowd, Frank J.; Johnson, Bart; Mariotti, Angelo (2016). Pharmacology and Therapeutics for Dentistry (7 ed.). Elsevier Health Sciences. p. 533. ISBN 9780323445955. Archived from the original on 2017-09-11.
    4. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    5. ↑ "Ifosfamide". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 8 December 2016.
    6. ↑ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 580. ISBN 9780857111562.
    7. 1 2 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.
    8. ↑ Foster, Corey, ed. (2010). The Washington Manual of Therapeutics (33 ed.). Wolters Kluwer | Lippincott Williams & Wilkins. p. 407.
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