Amifostine


Generic Medicine Info
Indications and Dosage
Intravenous
Prophylaxis of xerostomia in patients undergoing radiotherapy for head and neck cancer
Adult: 200 mg/m2 once daily via infusion over 3 min, starting w/in 15-30 min prior to radiotherapy.

Intravenous
Cytoprotective agent in chemotherapy
Adult: Initially, 910 mg/m2 once daily via infusion over 15 min, starting 30 min prior to chemotherapy. Subsequent doses reduced to 740 mg/m2 if patient is unable to tolerate the full dose. For cisplatin doses <100 mg/m2: 740 mg/m2.
Reconstitution
Add 9.7 mL of sterile NaCl 0.9% inj to a 500 mg vial to prepare a 10 mL soln containing 50 mg/mL. For use prior to chemotherapy, dilute further in sterile NaCl 0.9% to a final concentration of 5-40 mg/mL.
Incompatibility
Y-site admin: Incompatible w/ aciclovir, amphotericin B, cefoperazone, chlorpromazine, cisplatin, ganciclovir, hydroxyzine, miconazole, minocycline, prochlorperazine edisilate. Syringe: Ceftriaxone.
Contraindications
Hypotension, dehydration. Lactation.
Special Precautions
Patient w/ CV or cerebrovascular disease (e.g. ischaemic heart disease, arrhythmias, CHF, history of stroke or transient ischaemic attack). Renal impairment. Pregnancy.
Adverse Reactions
Reduction in BP; nausea, vomiting; flushing, chills, malaise, fever, dizziness, somnolence, hiccups, sneezing, cough; rash, pruritus, urticaria, chest tightness, laryngeal oedema; severe acute allergic reaction; pain, inflammation, bruising, phlebitis, and local swelling at inj site. Rarely, loss of consciousness, tachycardia, bradycardia, arrhythmias (e.g. atrial fibrillation/flutter, supraventricular tachycardia), chest pain, myocardial ischaemia, MI, cardiac and resp arrest, convulsions, dyspnoea, apnoea, hypoxia, renal failure, hypocalcaemia, transient HTN.
Potentially Fatal: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, bullous toxicity.
MonitoringParameters
Monitor BP every 5 min during infusion (prior to chemotherapy) or at least before and immediately after infusion (prior to radiotherapy); and thereafter as clinically indicated. Monitor serum Ca levels in patients at risk of hypocalcaemia. Evaluate for cutaneous reactions prior to each dose.
Overdosage
Symptoms: Hypotension, nausea, vomiting, hypocalcaemia. Management: Supportive treatment.
Drug Interactions
May potentiate hypotension w/ antihypertensive medications.
Action
Description: Amifostine, an aminothiol prodrug, is dephosphorylated by alkaline phosphatase in tissues into an active free thiol metabolite, WR-1065, which protects noncancerous cells against the toxic effects of antineoplastics and ionising radiation. WR-1065 binds and detoxify reactive metabolites and acts as scavenger of free radicals.
Pharmacokinetics:
Distribution: Distributed into normal tissues w/ high concentrations in bone marrow, GI mucosa, skin, liver and salivary glands (active metabolite). Volume of distribution: 3.5L. Plasma protein binding: 4%.
Metabolism: Metabolised in the liver by alkaline phosphatase via dephosphorylation to the active metabolite, WR-1065; then further metabolised to a less active disulfide metabolite, WR-33278.
Excretion: Via urine (as metabolites). Elimination half-life: <10 min.
Chemical Structure

Chemical Structure Image
Amifostine

Source: National Center for Biotechnology Information. PubChem Database. Amifostine, CID=2141, https://pubchem.ncbi.nlm.nih.gov/compound/Amifostine (accessed on Jan. 20, 2020)

Storage
Store between 20-25°C. Reconstituted soln: Store at 25°C (stable for 5 hr) or 2-8°C (stable for 24 hr).
ATC Classification
V03AF05 - amifostine ; Belongs to the class of detoxifying agents used in antineoplastic treatment.
References
Amifostine Injection, Powder, Lyophilized, for Solution (Bedford Laboratories). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 07/09/2016.

Anon. Amifostine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/09/2016.

Buckingham R (ed). Amifostine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/09/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Amifostine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 07/09/2016.

Disclaimer: This information is independently developed by MIMS based on Amifostine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $139 a year.
Sign up for free
Already a member? Sign in