WARNINGS
See boxed Warnings.
Concurrent administration of HEXALEN® capsules and antidepressants of the monoamine oxidase (MAO) inhibitor class may cause severe orthostatic hypotension. Four patients, all over 60 years of age, were reported to have experienced symptomatic hypotension after 4 to 7 days of concomitant therapy with HEXALEN® capsules and MAO inhibitors.
HEXALEN® capsules causes mild to moderate myelosuppression and neurotoxicity. Blood counts and a neurologic examination should be performed prior to the initiation of each course of therapy and the dose of HEXALEN® capsules adjusted as clinically indicated (see Dosage and Administration).
Pregnancy: Category D
HEXALEN® capsules has been shown to be embryotoxic and teratogenic in rats and rabbits when given at doses 2 and 10 times the human dose. HEXALEN® capsules may cause fetal damage when administered to a pregnant woman. If HEXALEN® capsules is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
PRECAUTIONS
General
Neurologic examination should be performed regularly (see Adverse Reactions).
Laboratory Tests
Peripheral blood counts should be monitored at least monthly, prior to the initiation of each course of HEXALEN® capsules, and as clinically indicated (see Adverse Reactions).
Drug Interactions
Concurrent administration of HEXALEN® capsules and antidepressants of the MAO inhibitor class may cause severe orthostatic hypotension (see Warnings section). Cimetidine, an inhibitor of microsomal drug metabolism, increased altretamine's half-life and toxicity in a rat model.
Data from a randomized trial of HEXALEN® capsules and cisplatin plus or minus pyridoxine in ovarian cancer indicated that pyridoxine significantly reduced neurotoxicity; however, it adversely affected response duration suggesting that pyridoxine should not be administered with HEXALEN® capsules and/or cisplatin (1).
Carcinogenesis, Mutagenesis and Impairment of Fertility
The carcinogenic potential of HEXALEN® capsules has not been studied in animals, but drugs with similar mechanisms of action have been shown to be carcinogenic. HEXALEN® capsules was weakly mutagenic when tested in strain TA100 of Salmonella typhimurium. HEXALEN® capsules administered to female rats 14 days prior to breeding through the gestation period had no adverse effect on fertility, but decreased post-natal survival at 120 mg/m2/day and was embryocidal at 240 mg/m2/day. Administration of 120 mg/m2/day HEXALEN® capsules to male rats for 60 days prior to mating resulted in testicular atrophy, reduced fertility and a possible dominant lethal mutagenic effect. Male rats treated with HEXALEN® capsules at 450 mg/m2/day for 10 days had decreased spermatogenesis, atrophy of testes, seminal vesicles and ventral prostate.
Pregnancy
Pregnancy Category D: see Warnings section.
Nursing Mothers
It is not known whether altretamine is excreted in human milk. Because there is a possibility of toxicity in nursing infants secondary to HEXALEN® capsules treatment of the mother, it is recommended that breast feeding be discontinued if the mother is treated with HEXALEN® capsules.
Pediatric Use
The safety and effectiveness of HEXALEN® capsules in children have not been established.
|
