No

Antidote

Reduce the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands. Reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer or nonsmall cell lung cancer. In these settings, the clinical data does not suggest that the effectiveness of cisplatin-based chemotherapy regimens is altered by amifostine.

C

Known hypersensitivity to aminothiol compounds or mannitol

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered

Patients who are hypotensive or in a state of dehydration should not receive amifostine. Patients receiving antihypertensive therapy that cannot be stopped for 24 hours preceding amifostine treatment also should not receive amifostine. Patients should be adequately hydrated prior to amifostine infusion and kept in a supine position during the infusion. Blood pressure should be monitored every 5 minutes during the infusion. If hypotension requiring interruption of therapy occurs, patients should be placed in the Trendelenburg position and given an infusion of normal saline using a separate I.V. line.

It is recommended that antiemetic medication, including dexamethasone 20 mg I.V. and a serotonin 5-HT₃ receptor antagonist be administered prior to and in conjunction with amifostine.

Reports of clinically relevant hypocalcemia are rare, but serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome

>10%:

Cardiovascular: Flushing; hypotension (62%)

Central nervous system: Chills, dizziness, somnolence

Gastrointestinal: Nausea/vomiting (may be severe)

Respiratory: Sneezing

Miscellaneous: Feeling of warmth/coldness, hiccups

<1%: Mild rashes, hypocalcemia, rigors

Symptoms of overdose include increased nausea and vomiting, hypotension

Treatment includes infusion of normal saline and other supportive measures, as clinically indicated

Increased toxicity: Special consideration should be given to patients receiving antihypertensive medications or other drugs that could potentiate hypotension

Store intact vials of lyophilized powder at room temperature (20°C to 25°C/68°F to 77°F)

Reconstitute with 9.7 mL of sterile 0.9% sodium chloride. The reconstituted solution (500 mg/10 mL) is chemically stable for up to 5 hours at room temperature (25°C) or up to 24 hours under refrigeration (2°C to 8°C).

Amifostine should be further diluted in 0.9% sodium chloride to a concentration of 5-40 mg/mL and is chemically stable for up to 5 hours at room temperature (25°C) or up to 24 hours under refrigeration (2°C to 8°C)

Prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite that can reduce the toxic effects of cisplatin. The free thiol is available to bind to, and detoxify, reactive metabolites of cisplatin; and can also act as a scavenger of free radicals that may be generated in tissues exposed to cisplatin.

Absorption: Oral: Poor

Distribution: V_d: 3.5 L

Metabolism: Hepatic dephosphorylation to two metabolites (WR-33278 and WR-1065)

Half-life: 9 minutes

Elimination: Renal; plasma clearance: 2.17 L/minute

Adults: I.V. (refer to individual protocols): 910 mg/m² administered once daily as a 15-minute I.V. infusion, starting 30 minutes prior to chemotherapy

Note: 15-minute infusion is better tolerated than more extended infusions. Further reductions in infusion times have not been systematically investigated. The infusion of amifostine should be interrupted if the systolic blood pressure (mm Hg) decreases significantly from the following baseline values:

Decrease of 20 if baseline systolic blood pressure <100

Decrease of 25 if baseline systolic blood pressure 100-119

Decrease of 30 if baseline systolic blood pressure 120-139

Decrease of 40 if baseline systolic blood pressure 140-179

Decrease of 50 if baseline systolic blood pressure greater than or equal to 180

Mean onset of hypotension is 14 minutes into the 15-minute infusion and the mean duration was 6 minutes. Hypotension should be treated with fluid infusion and postural management of the patient (supine or Trendelenburg position). If the blood pressure returns to normal within 5 minutes and the patient is asymptomatic, the infusion may be restarted so that the full dose of amifostine may be administered. If the full dose of amifostine cannot be administered, the dose of amifostine for subsequent cycles should be 740 mg/m².

Blood pressure should be monitored every 5 minutes during the infusion

Drowsiness is common

Hypotension is common and may be additive with psychotropics

No information available to require special precautions

Nausea/vomiting (may be severe)

This I.V. medication is given to help reduce side effects of your chemotherapy. Report immediately any nausea; you will be given medication. Report chills, severe dizziness, tremors or shaking, or sudden onset of hiccups. Breast-feeding precautions: Do not breast-feed.

Injection: 500 mg

Adamson PC, Balis FM, Belasco JE, et al, "A Phase I Trial of Amifostine (WR-2721) and Melphalan in Children With Refractory Cancer," Cancer Res, 1995, 55(18): 4069-72.

Bukowski R, "Cytoprotection in the Treatment of Pediatric Cancer: Review of Current Strategies in Adults and Their Application to Children," Med Pediatr Oncol, 1999, 32(2):124-34.

Schuchter LM, "Guidelines for the Administration of Amifostine," Semin Oncol, 1996, 23(4 Suppl 8):40-3.

Shaw LM, Bonner H, and Lieberman R, "Pharmacokinetic Profile of Amifostine," Semin Oncol, 1996, 23(4 Suppl 8):18-22.

Spencer CM and Goa KL, "Amifostine. A Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential as a Radioprotector and Cytotoxic Chemoprotector," Drugs, 1995, 50(6):1001-31.