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Amifostine (Ethyol)
( am-ih- FOS-teen)
Pregnancy Category: C Ethyol (Rx)

Classification: Cytoprotective drug

Action/Kinetics: Amifostine, an organic thiophosphate prodrug, is dephosphorylated by alkaline phosphatase in tissue to the active free thiol metabolite. The thiol metabolite reduces the toxic effects of cisplatin. The abilitiy to protect normal tissues differentially is due to the higher capillary alkaline phosphatase activity, higher pH, and better vascularity of normal tissues compared with tumor tissue. This results in a more rapid generation of the active thiol metabolite as well as greater uptake into tissues. The higher levels of the thiol metabolite in normal tissues binds to, and thus detoxifies, reactive metabolites of cisplatin; the thiol metabolite can also scavange free radicals that may be generated in tissues exposed to cisplatin. Rapidly cleared from the plasma. t 1/2, distribution: less than 1 min; t 1/2, elimination: about 8 min. The thiol metabolite is further broken down to a disulfide metabolite that is less active.

Uses: To decrease cumulative renal toxicity due to repeated use of cisplatin in clients with advanced ovarian cancer and in those with non-small-cell lung cancer. Treat postoperative radiation-induced dry mouth in clients with head and neck cancer where the radiation port includes a significant part of the parotid glands. Investigational: Protect lung fibroblasts from damage by paclitaxel.

Contraindications: Hypersensivity to aminothiol compounds or mannitol. Use in hypotensive or dehydrated clients, in those on antihypertensive therapy that cannot be terminated for 24 hr, and in clients receiving chemotherapy for malignancies that are potentially curable (e.g., certain malignancies of germ cell origin). Use in clients receiving definitive radiotherapy, except during a clinical trial. Lactation.

Special Concerns: Safety has not been determined in clients over 70 years of age or in those with preexisting CV or cerebrovascular conditions, such as ischemic heart disease, arrhythmias, CHF, or history of stroke or transient ischemic attacks. Use with caution in those where N&V or hypotension may be more likely to have serious consequences. Safety and efficacy have not been determined in children.

Side Effects: CV: Transient decrease in BP, hypotension. GI: Severe N&V. CNS: Dizziness, somnolence, reversible loss of consciousness (rare). Hypersensitivity: Mild skin rash, fever, chills, dyspnea, urticaria, rigors, erythema multiforme; rarely, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis. Miscellaneous: Flushing or feeling of warmth, chills or feeling of coldness, hiccoughs, sneezing, hypocalcemia.

Drug Interactions: Amifostine may cause hypotension in clients receiving antihypertensive drugs or other drugs that may potentiate hypotension.

How Supplied: Powder (lyophilized) for injection: 500 mg

?IV Infusion Cytoprotective agent used with cisplatin.
Initial: 910 mg/m 2 given once daily as a 15-min IV infusion, starting within 30 min prior to cisplatin chemotherapy.
Reduce dry mouth in postoperative radiation treatment for head and neck cancer.
200 mg/m 2 given once daily as a 3 min IV infusion, starting 15 to 30 min before standard fraction radiation therapy.

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