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Ifosfamide
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<h2 id="medical-uses">Medical uses</h2> <p>It is given as a treatment for a variety of <a href="/facts/Cancer/PVW6n1D0">cancers</a>, including: </p> <ul><li><a href="/facts/Testicular_cancer/v8qGnvRm">Testicular cancer</a></li> <li><a href="/facts/Breast_cancer/6hME580v">Breast cancer</a></li> <li><a href="/facts/Lymphoma/418wcMEl">Lymphoma</a> (Hodgkin and non-Hodgkin)</li> <li><a href="/facts/Soft_tissue_sarcoma/9XWx62rP">Soft tissue sarcoma</a></li> <li><a href="/facts/Osteosarcoma/FnlFbprC">Osteosarcoma</a> or <a href="/facts/Bone_tumor/YRqXtJwY">bone tumor</a></li> <li><a href="/facts/Lung_cancer/LHLdR454">Lung cancer</a></li> <li><a href="/facts/Cervical_cancer/99vngUyd">Cervical cancer</a></li> <li><a href="/facts/Ovarian_cancer/fsWbh3Tn">Ovarian cancer</a></li></ul> <h3>Administration</h3> <p>It is a white <a href="/facts/Powder_(substance)/PGd3HwHE">powder</a> which, when prepared for use in <a href="/facts/Chemotherapy/fWTLbaUT">chemotherapy</a>, becomes a clear, colorless fluid. The delivery is <a href="/facts/Intravenous/AwwuD3Nu">intravenous</a>. </p><p>Ifosfamide is often used in conjunction with <a href="/facts/Mesna/BYLAl5pG">mesna</a> to avoid <a href="/facts/Internal_bleeding/3cj5g8YQ">internal bleeding</a> in the patient, in particular <a href="/facts/Hemorrhagic_cystitis/G19n5N4U">hemorrhagic cystitis</a>. </p><p>Ifosfamide is given quickly, and in some cases can be given as quickly as an hour. </p> <h2 id="mechanism-of-action">Mechanism of action</h2> <p>Ifosfamide is a DNA-damaging alkylating agent, belonging to the same class of chemotherapy drugs as <a href="/facts/Cyclophosphamide/eTXHmLFV">cyclophosphamide</a>. 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.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> </p> <h2 id="side-effects">Side effects</h2> <p>Hemorrhagic cystitis is rare when ifosfamide is given with <a href="/facts/Mesna/BYLAl5pG">mesna</a>. A common and dose-limiting side effect is <a href="/facts/Encephalopathy/mbArdl2s">encephalopathy</a> (brain dysfunction).<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> It occurs in some form in up to 50% of people receiving the agent. The reaction is probably mediated by <a href="/facts/Chloroacetaldehyde/h6sW22cz">chloroacetaldehyde</a>, one of the breakdown products of the ifosfamide molecule, which has chemical properties similar to <a href="/facts/Acetaldehyde/QllLbSUe">acetaldehyde</a> and <a href="/facts/Chloral_hydrate/KhDz2HhD">chloral hydrate</a>. The symptoms of ifosfamide encephalopathy can range from mild (difficulty concentrating, fatigue), to moderate (<a href="/facts/Delirium/f1zdzAc5">delirium</a>, <a href="/facts/Psychosis/cVGd7MKK">psychosis</a>), to severe (<a href="/facts/Status_epilepticus/2mk2Bxv3">nonconvulsive status epilepticus</a> or <a href="/facts/Coma/N9oQ7g7R">coma</a>). 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 <a href="/facts/National_Cancer_Institute/R4KbY7Pb">National Cancer Institute</a> or the Meanwell criteria (grade I–IV). Previous brain problems and low levels of <a href="/facts/Albumin/gDmSgAH2">albumin</a> 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 <a href="/facts/Methylene_blue/NIo9Xaag">methylene blue</a>, 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 <a href="/facts/Thiamine/37RC4MCS">thiamine</a>, and <a href="/facts/Kidney_dialysis/KQgUGz8p">dialysis</a> as a rescue modality.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> </p><p>Ifosfamide may also cause a <a href="/facts/Normal_anion_gap_acidosis/B017Psda">normal anion gap acidosis</a>, specifically <a href="/facts/Renal_tubular_acidosis/PcrVnYW5">renal tubular acidosis</a> type 2.<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016. <a href="https://www.drugs.com/monograph/ifosfamide.html" target="_blank">https://www.drugs.com/monograph/ifosfamide.html</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016. <a href="https://www.drugs.com/monograph/ifosfamide.html" target="_blank">https://www.drugs.com/monograph/ifosfamide.html</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016. <a href="https://www.drugs.com/monograph/ifosfamide.html" target="_blank">https://www.drugs.com/monograph/ifosfamide.html</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016. <a href="https://www.drugs.com/monograph/ifosfamide.html" target="_blank">https://www.drugs.com/monograph/ifosfamide.html</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>"Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016. <a href="https://www.drugs.com/monograph/ifosfamide.html" target="_blank">https://www.drugs.com/monograph/ifosfamide.html</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>"Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016. <a href="https://www.drugs.com/monograph/ifosfamide.html" target="_blank">https://www.drugs.com/monograph/ifosfamide.html</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>"Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016. <a href="https://www.drugs.com/monograph/ifosfamide.html" target="_blank">https://www.drugs.com/monograph/ifosfamide.html</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Dowd FJ, Johnson B, Mariotti A (2016). Pharmacology and Therapeutics for Dentistry (7th ed.). Elsevier Health Sciences. p. 533. ISBN 9780323445955. Archived from the original on 11 September 2017. <a href="9780323445955" target="_blank">9780323445955</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>"Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016. <a href="https://www.drugs.com/monograph/ifosfamide.html" target="_blank">https://www.drugs.com/monograph/ifosfamide.html</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>"Ifosfamide". The American Society of Health-System Pharmacists. Archived from the original on 7 May 2017. Retrieved 8 December 2016. <a href="https://www.drugs.com/monograph/ifosfamide.html" target="_blank">https://www.drugs.com/monograph/ifosfamide.html</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>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. <a href="/wiki/World_Health_Organization" target="_blank">/wiki/World_Health_Organization</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>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. PMID 10469896. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Ajithkumar T, Parkinson C, Shamshad F, Murray P (March 2007). "Ifosfamide encephalopathy". Clinical Oncology. 19 (2): 108–114. doi:10.1016/j.clon.2006.11.003. PMID 17355105. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Ajithkumar T, Parkinson C, Shamshad F, Murray P (March 2007). "Ifosfamide encephalopathy". Clinical Oncology. 19 (2): 108–114. doi:10.1016/j.clon.2006.11.003. PMID 17355105. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Foster C, ed. (2010). The Washington Manual of Therapeutics (33 ed.). Wolters Kluwer | Lippincott Williams & Wilkins. p. 407. <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> </ol>