Amifostine

Intravenous
Prophylaxis of xerostomia in patients undergoing radiotherapy for head and neck cancer

Intravenous
Cytoprotective agent in chemotherapy

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.

Y-site admin: Incompatible w/ aciclovir, amphotericin B, cefoperazone, chlorpromazine, cisplatin, ganciclovir, hydroxyzine, miconazole, minocycline, prochlorperazine edisilate. Syringe: Ceftriaxone.

Hypotension, dehydration. Lactation.

Patient w/ CV or cerebrovascular disease (e.g. ischaemic heart disease, arrhythmias, CHF, history of stroke or transient ischaemic attack). Renal impairment. Pregnancy.

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.

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.

Symptoms: Hypotension, nausea, vomiting, hypocalcaemia. Management: Supportive treatment.

May potentiate hypotension w/ antihypertensive medications.

Description:
Mechanism of Action: 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.

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

Store between 20-25°C. Reconstituted soln: Store at 25°C (stable for 5 hr) or 2-8°C (stable for 24 hr).

Supportive Care Therapy

V03AF05 - amifostine ; Belongs to the class of detoxifying agents used in antineoplastic treatment.

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.