ratogenic Effects: Category B.
In the teratology studies conducted with fosaprepitant and aprepitant, the highest systemic exposures to aprepitant were obtained following oral administration of aprepitant. Teratology studies performed in rats at oral doses of aprepitant up to 1000 mg/kg twice daily (plasma AUC0-24hr of 31.3 mcg•hr/mL, about 1.6 times the human exposure at the recommended dose) and in rabbits at oral doses up to 25 mg/kg/day (plasma AUC0-24hr of 26.9 mcg•hr/mL, about 1.4 times the human exposure at the recommended dose) revealed no evidence of impaired fertility or harm to the fetus due to aprepitant. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
Aprepitant is excreted in the milk of rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for possible serious adverse reactions in nursing infants from aprepitant and because of the potential for tumorigenicity shown for aprepitant in rodent carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
In 2 well-controlled chemotherapy-induced nausea and vomiting clinical studies, of the total number of patients (N=544) treated with oral aprepitant, 31% were 65 and over, while 5% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Greater sensitivity of some older individuals cannot be ruled out. Dosage adjustment in the elderly is not necessary.
ADVERSE REACTIONS
The overall safety of aprepitant was eva luated in approximately 4900 individuals.
Since EMEND for Injection is converted to aprepitant, those adverse experiences associated with aprepitant might also be expected to occur with EMEND for Injection.
Fosaprepitant (intravenous formulation)
In a randomized, open-label, incomplete crossover, bioequivalence study, 66 subjects were dosed with 115 mg of EMEND for Injection intravenously and 72 subjects received 125 mg of aprepitant orally. Systemic exposure of 115 mg of intravenous EMEND for Injection is equivalent to 125 mg oral aprepitant. The following clinical adverse experiences, regardless of causality, were reported in subjects dosed with EMEND for Injection: infusion site pain, 5 (7.6%); infusion site induration, 1 (1.5%); headache, 2 (3%).
Oral Aprepitant
Highly Emetogenic Chemotherapy
In 2 well-controlled clinical trials in patients receiving highly emetogenic cancer chemotherapy, 544 patients were treated with aprepitant during Cycle 1 of chemotherapy and 413 of these patients continued into the Multiple-Cycle extension for up to 6 cycles of chemotherapy. Oral aprepitant was given in combination with ondansetron and dexamethasone and was generally well tolerated. Most adverse experiences reported in these clinical studies were described as mild to moderate in intensity.
In Cycle 1, clinical adverse experiences were reported in approximately 69% of patients treated with the aprepitant regimen compared with approximately 68% of patients treated with standard |
