Amifostine

ETHYOL is a cytoprotective agent indicated for: – reduction of cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. – reduction of 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. Limitation of Use Avoid the use of ETHYOL in settings where chemotherapy can produce a significant survival benefit or cure, or in patients receiving definitive radiotherapy.

ETHYOL 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. The higher concentration of the thiol metabolite in normal tissues is available to bind to, and thereby detoxify, reactive metabolites of cisplatin.

– For reduction of cumulative renal toxicity with chemotherapy, the recommended starting dose is 910 mg/m 2 administered once daily as a 15-minute intravenous infusion, starting 30 minutes prior to chemotherapy. – For reduction of moderate to severe xerostomia from radiation of the head and neck, the recommended dose is 200 mg/m 2 administered once daily as a 3-minute intravenous infusion, starting 15-30 minutes prior to standard fraction radiation therapy (1.8-2.0 Gy).

ETHYOL is contraindicated in patients with known hypersensitivity to aminothiol compounds.

– Hypotension and Cardiovascular Events: Patients who are hypotensive or dehydrated should not receive ETHYOL. If interruption of antihypertensive therapy is possible, interrupt antihypertensive therapy 24 hours prior to ETHYOL administration. Monitor blood pressure during infusion, interrupt and restart infusion if decrease in systolic blood pressure is observed. Do not administer ETHYOL to hypotensive patients who are taking antihypertensive therapy that cannot be stopped for 24 hours prior to ETHYOL administration. – Severe Cutaneous Reactions: Monitor patients prior to, during, and weeks after administration for severe cutaneous reactions. Discontinue for cutaneous reactions or lesions appearing outside of the injection site/radiation port or on the palms or soles. – Hypersensitivity: Discontinue for severe acute allergic reactions.

The following serious adverse reactions are discussed in greater detail in other sections of the labeling: – Hypotension and Cardiovascular Events – Severe Cutaneous Reactions – Hypersensitivity – Nausea and Vomiting – Hypocalcemia Most common adverse reactions are hypotension, nausea and vomiting.

Closely monitor patients receiving anti-hypertensive medications or other drugs that could cause or potentiate hypotension. – Closely monitor patients receiving anti-hypertensive medications or other drugs that could cause or potentiate hypotension.

Store the lyophilized dosage form at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).