Amifostine

Indications

Amifostine is used for: Nephrotoxicity (Indicated to reduce cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer), Xerostomia

Adult Dose

Nephrotoxicity 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 Xerostomia 200 mg/m² IV (3-minute infusion), 15-30 minutes before radiation therapy 500 mg SC qDay prior to radiation therapy

Child Dose

Safety and efficacy not established

Renal Dose

Administration

Ensure adequate hydration and premedicate with antiemetic treatment 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

Contra Indications

Hypersensitivity to aminothiol, monitor closely during and after IV

Precautions

Patients should be adequately hydrated prior to the Amifostine for Injection infusion and blood pressure should be monitored 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 Lactation: excretion in milk unknown/not recommended

Pregnancy-Lactation

Pregnancy When used in combination with cisplatin, refer to cisplatin full prescribing information Verify pregnancy status in females of reproductive potential prior to initiating therapy Based on findings in animals, therapy can cause fetal harm when administered to a pregnant woman There are no available data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes Advise pregnant women and females of reproductive potential of the potential risk to a fetus Animal data In animal reproduction studies, intravenous administration to pregnant rabbits during organogenesis was embryotoxic at doses approximately sixty percent of recommended dose in humans based on body surface area Infertility Based on findings from animal studies, therapy may impair fertility in males of reproductive potential Lactation When used in combination with cisplatin, refer to cisplatin full prescribing information for lactation information There are no data on presence of amifostine or metabolites in human milk, effects on breastfed child, or on milk production Because of potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment

Interactions

Special consideration should be given to the administration of Amifostine for Injection in patients receiving antihypertensive medications or other drugs that could cause or potentiate hypotension.

Adverse Effects

Side effects of Amifostine : >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

Mechanism of Action

Thiol metabolite binds to reactive metabolites of cisplatin and scavenges free radicals