iated fever or other constitutional symptoms
Amifostine should be permanently discontinued for serious or severe cutaneous reactions (see WARNINGS and ADVERSE REACTIONS) or for cutaneous reactions associated with fever or other constitutional symptoms not known to be due to another etiology. Amifostine should be withheld and dermatologic consultation and biopsy considered for cutaneous reactions or mucosal lesions of unknown etiology appearing outside of the injection site and for erythematous, edematous or bullous lesions on the palms of the hand or soles of the feet. Reinitiation of Amifostine should be at the physician's discretion based on medical judgment and appropriate dermatologic eva luation.
Allergic Reactions
In case of severe acute allergic reactions Amifostine should be immediately and permanently discontinued. Epinephrine and other appropriate measures should be available for treatment of serious allergic events such as anaphylaxis.
Drug Interactions
Special consideration should be given to the administration of Amifostine in patients receiving antihypertensive medications or other drugs that could cause or potentiate hypotension.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long term animal studies have been performed to eva luate the carcinogenic potential of Amifostine. Amifostine was negative in the Ames test and in the mouse micronucleus test. The free thiol metabolite was positive in the Ames test with S9 microsomal fraction in the TA1535 Salmonella typhimurium strain and at the TK locus in the mouse L5178Y cell assay. The metabolite was negative in the mouse micronucleus test and negative for clastogenicity in human lymphocytes.
Pregnancy
Pregnancy Category C. Amifostine has been shown to be embryotoxic in rabbits at doses of 50 mg/kg, approximately sixty percent of the recommended dose in humans on a body surface area basis. There are no adequate and well-controlled studies in pregnant women.
Amifostine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mohers
No information is available on the excretion of Amifostine or its metabolites into human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants, it is recommended that breast feeding be discontinued if the mother is treated with Amifostine.
Pediatric Use
The safety and effectiveness in pediatric patients have not been established.
Geriatric Use
The clinical studies did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in elderly patients.
Adverse Reactions
Controlled Trials
In the randomized study of patients with ovarian cancer given Amifostine at a dose of 910 mg/m2 prior to chemotherapy, transient hypotension was observed in 62% of patients treated. The mean time of onset was 14 minutes into the 15-minute period of Amifostine infusion, and the mean duration was 6 minutes. In some cases, the infusion had to be prematurely terminated due to a more pronounced drop in systolic blood press |
