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.
Known hypersensitivity to aminothiol compounds or
The U.S. Food and Drug Administration (FDA) currently recommends that
procedures for proper handling and disposal of antineoplastic agents be
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
Cardiovascular: Flushing; hypotension (62%)
Central nervous system: Chills, dizziness, somnolence
Gastrointestinal: Nausea/vomiting (may be severe)
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
Store intact vials of lyophilized powder at room temperature
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: Vd: 3.5 L
Metabolism: Hepatic dephosphorylation to two metabolites (WR-33278 and
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
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
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
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
|Mental Health: Effects
on Mental Status|
Drowsiness is common
Effects on Psychiatric
Hypotension is common and may be additive with
|Dental Health: Local
No information available to require special precautions
Effects on Dental Treatment|
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.
"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
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.
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