Dosing and uses of Ethyol (amifostine)
Adult dosage forms and strengths
powder for injection
- 500mg/vial
Nephrotoxicity
Indicated to reduce cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer
910 mg/m² IV (15-minute infusion), 30 minutes before chemotherapy
Blood pressure should be followed following its administration and interrupted if systolic blood pressure decreases signficantly from baseline as described below
Interrupt Therapy If Systolic Blood Pressure Baseline Decreased
- Decreased by 20 mm Hg if baseline <100
- Decreased by 25 mm Hg if baseline <100-119
- Decreased by 30 mm Hg if baseline <120-139
- Decreased by 40 mm Hg if baseline <140-179
- Decreases by 50 mm Hg if baseline ≥180
Xerostomia
Indicated to reduce 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
200 mg/m² IV (3-minute infusion), 15-30 minutes before radiation therapy
500 mg SC qDay prior to radiation therapy
Chemoprotective Agent (Orphan)
Orphan indications
- Chemoprotection for cisplatin in the treatment of metastatic melanoma
- Reduction of incidence and severity of toxicities associated with cisplatin administration
- Chemoprotection for cyclophosphamide in the treatment of advanced ovarian carcinoma
- Treatment of myelodysplastic syndromes
Orphan indications sponsor
- Medimmune Oncology, Inc; One MedImmune Way; Gaithersburg, MD 20878
Administration
Ensure adequate hydration and premedicate with antiemetic treatment
Pediatric dosage forms and strengths
Safety and efficacy not established
Ethyol (amifostine) adverse (side) effects
>10%
Nausea/vomiting (96%)
Hypotension (61%) - discontinue infusion if significant BP drop
1-10%
Hypocalcemia (1%)
Stevens-Johnson syndrome (1%)
Frequency not defined
Chills/feeling of coldness
Flushing/feeling of warmth
Dizziness
Fever
Somnolence
Rash
Malaise
Hiccups
Sneezing
Warnings
Contraindications
Hypersensitivity to aminothiol, monitor closely during and after IV
Cautions
Cardiovascular disease, hypocalcemia, hypotension, cutaneous reactions, or nausea/vomiting may occur
Ensure adequate hydration
Do not give to patients receiving definitive radiotherapy except in the context of a clinical trial, since there are at present insufficient data to exclude a tumor-protective effect in this setting; amifostine was studied only with standard fractionated radiotherapy and only when ≥75% of both parotid glands were exposed to radiation
Use caution in hypotension and cerebrovascular disease
Interrupt antihypertensive therapy 24 hr before treatment; patients unable to safely interupt antihypertensive therapy should not recieve amifostine
Pregnancy and lactation
Pregnancy category: C
Lactation: excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ethyol (amifostine)
Mechanism of action
Thiol metabolite binds to reactive metabolites of cisplatin and scavenges free radicals
Pharmacokinetics
Half-Life: 8 min
Metabolite: Free thioL
Metabolism: Liver
Vd: 3.5 L
Half-life: 8-9 min
Excretion: Urine
Administration
IV Incompatibilities
Y-site: acyclovir, amphotericin B, cefoperazone, chlorpromazine, cisplatin, ganciclovir, hydroxyzine, minocycline, prochlorperazine
IV Compatibilities
Y-site (partial list): amikacin, ampicillin, carboplatin, cefazolin, ceftriaxone, cefoxitin, clindamycin, dopamine, furosemide, heparin, lorazepam, MgSO4, metoclopramide, morphine, ondansetron, NaHCO3, trimethoprim/sulfamethoxazole, vancomycin
IV Preparation
Reconstitute with 9.5 mL 0.9% NaCL
Amifostine should be further diluted in 0.9% NaCl to a concentration of 5-40 mcg/mL
IV Administration
Infuse over 15 min before chemotherapy
Infuse over 3 min before radiation treatment
Administration as a longer infusion is associated with a higher incidence of adverse effects
Storage
Refrigerate lyophilized powder
