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Amifostine

NEO PLASTIC DISORDERS

IMMUNOSTIMULANTS - [ NEO PLASTIC DISORDERS ]

Amifostine is a sulfydryl compound. Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite. This metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. The ability of ETHYOL to differentially protect normal tissues is attributed to the higher capillary alkaline phosphatase activity, higher pH and better vascularity of normal tissues relative to tumor tissue, which results in a more rapid generation of the active thiol metabolite as well as a higher rate constant for uptake into cells. (1,2)

To reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. To reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands (2)

Known hypersensitivity to aminothiol compounds (2)

Hypotension Serious cutaneous and anaphylactic reactions Nausea and vomiting Hypocalcemia Occasionally apnea, dyspnea, hypoxia, tachycardia, bradycardia, extrasystoles, chest pain, myocardial ischemia and convulsion Rarely renal failure, myocardial infarction, respiratory arrest, cardiac arrest and exacerbation of pre-existing hypertension (2)

Special consideration should be given to the administration of amifostine in patients receiving antihypertensive medications or other drugs that could cause or potentiate hypotension. ‘ (2)

Amifostine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is recommended that breast feeding be discontinued if the mother is treated with amifostine The safety and effectiveness in pediatric patients have not been established Dose selection for an elderly patient should be cautious Caution in renal impairment (2)

For reduction of cumulative renal toxicity associated with chemotherapy: The recommended starting dose of amifostine is 910 mg/m2 administered once daily as a 15-minute i.v. infusion, starting 30 minutes prior to chemotherapy. For Reduction of Moderate to Severe Xerostomia from Radiation of the Head and Neck: The recommended dose of amifostine is 200 mg/m2 administered once daily as a 3-minute i.v. infusion. It is recommended that antiemetic medication be administered prior to and in conjunction with amifostine starting 15-30 minutes prior to standard fraction radiation therapy (1.8-2.0 Gy). (2)

1.Krensky AM, Bennett WM, Vincenti F. Immunosuppressants, Tolerogens and Immunostimulants. In: Brunton L, Chabner B, Knollmann B eds. Goodman & Gilman’s The Pharmacological basis of Therapeutics. 12th ed. China: McGraw Hill; 2011. P1005-31. 2. Ethyol [Internet]. [cited 2013 October 6]. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020221s024lbl.pdf