mal studies, almotriptan produced developmental toxicity (increased embryolethality and fetal skeletal variations, and decreased offspring body weight) at doses greater than those used clinically. There are no adequate and well-controlled studies in pregnant women; therefore, AXERT® (almotriptan malate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
When almotriptan (125, 250, 500, or 1000 mg/kg/day) was administered orally to pregnant rats throughout the period of organogenesis, increased incidences of fetal skeletal variations (decreased ossification) were noted at a dose of 250 mg/kg/day or greater and an increase in embryolethality was seen at the highest dose. The no-effect dose for embryo-fetal developmental toxicity in rats (125 mg/kg/day) is approximately 100 times the maximum recommended human dose (MRHD) of 25 mg/day on a body surface area (mg/m2) basis. Similar studies in pregnant rabbits conducted with almotriptan (oral doses of 5, 20, or 60 mg/kg/day) demonstrated increases in embryolethality at the highest dose. The no-effect dose for embryo-fetal developmental toxicity in rabbits (20 mg/kg/day) is approximately 15 times the MRHD on a mg/m2 basis. When almotriptan (25, 100, or 400 mg/kg/day) was administered orally to rats throughout the periods of gestation and lactation, gestation length was increased and litter size and offspring body weight were decreased at the highest dose. The decrease in pup weight persisted throughout lactation. The no-effect dose in this study (100 mg/kg/day) is 40 times the MRHD on a mg/m2 basis.
8.2 Labor and Delivery
The effect of AXERT® on labor and delivery in humans is unknown.
8.3 Nursing Mothers
It is not known whether almotriptan is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when AXERT® is administered to a nursing woman. Levels of almotriptan in rat milk were up to 7 times higher than in rat plasma.
8.4 Pediatric Use
Safety and efficacy of AXERT® in pediatric patients under the age of 12 years have not been established. The pharmacokinetics, efficacy, and safety of AXERT® have been eva luated in adolescent patients, age 12 to 17 years [see CLINICAL PHARMACOLOGY (12.3) and CLINICAL STUDIES (14.2)].
In a clinical study, AXERT® 6.25 mg and 12.5 mg were found to be effective for the relief of migraine headache pain in adolescent patients age 12 to 17 years. Efficacy on migraine-associated symptoms (nausea, photophobia, and phonophobia) was not established. The most common adverse reactions (incidence of ≥1%) associated with AXERT® treatment were dizziness, somnolence, headache, paresthesia, nausea, and vomiting [see ADVERSE REACTIONS (6.1)]. The safety and tolerability profile of AXERT® treatment in adolescents is similar to the profile observed in adults.
Postmarketing experience with other triptans include a limited number of reports that describe pediatric patients who have experienced clinically serious adverse events that are similar in nature to those reported rarely in adults.
8.5 Geriatric Use
Clinical studies of AXERT® did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger subjects. Clearance of almotriptan was lower in elderly volunteers than in younger individuals, but there were no observed differences in the safety and tolerability between the two populations [see |
