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Carcinogenesis/ Mutagenesis and Impairment of Fertility: No evidence of carcinogenicity was found in studies in which d, l-amphetamine (enantiomer ratio of 1: 1) was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/ kg/ day in male mice, 19 mg/ kg/ day in female mice, and 5 mg/ kg/ day in male and female rats. These doses are approximately 2.4, 1.5, and 0.8 times, respectively, the maximum recommended human dose of 30 mg/ day on a mg/ m 2 body surface area basis. 0
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PLASMA CONCENTRATIONS OF DEXTRO AND LEVOAMPHETAMINE (ng/ mL) DEXTROAMPHETAMINE
LEVOAMPHETAMINE
ADDERALL XR TM 20 mg qd
ADDERALL ® 10 mg bid ADDERALL ® 10 mg bid
ADDERALL XR TM 20 mg qd Amphetamine, in the enantiomer ratio present in ADDERALL ® (immediate-release)( d-to l-ratio of 3: 1), was not clastogenic in the mouse bone marrow micronucleus test in vivo and was negative when tested in the E. coli component of the Ames test in vitro. d, l-Amphetamine (1: 1 enantiomer ratio) has been reported to produce a positive response in the mouse bone marrow micronucleus test, an equivocal response in the Ames test, and negative responses in the in vitro sister chromatid exchange and chromosomal aberration assays. Amphetamine, in the enantiomer ratio present in ADDERALL ® (immediate-release)( d-to l-ratio of 3: 1), did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/ kg/ day (approximately 5 times the maximum recommended human dose of 30 mg/ day on a mg/ m 2 body surface area basis). Pregnancy: Pregnancy Category C. Amphetamine, in the enantiomer ratio present in ADDERALL ® (d-to l-ratio of 3: 1), had no apparent effects on embryofetal morphological development or survival when orally administered to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 6 and 16 mg/ kg/ day, respectively. These doses are approximately 1.5 and 8 times, respectively, the maximum recommended human dose of 30 mg/ day on a mg/ m 2 body surface area basis. Fetal malformations and death have been reported in mice following parenteral administration of d-amphetamine doses of 50 mg/ kg/ day (approximately 6 times the maximum recommended human dose of 30 mg/ day on a mg/ m 2 basis) or greater to pregnant animals. Administration of these doses was also associated with severe maternal toxicity. A number of studies in rodents indicate that prenatal or early postnatal exposure to amphetamine (d-or d, l-), at doses similar to those used clinically, can result in long-term neurochemical and behavioral alterations. Reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function. There are no adequate and well-controlled studies in pregnant women. There has been one report of severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia (vater association) in a baby born to a woman who took dextroamphetamine sulfate with lovastatin during the first trimester of pregnancy. Amphetamines should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects: Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude. Usage in Nursing Mothers: Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing. Pediatric Use: ADDERALL XRª is indicated for use in children 6 years of age and older. Use in Children Under Six Years of Age: Effects of ADDERALL XRª in 3-5 year olds have not been studied. Long-term effects of amphetamines in children have not been well established. Amphetamines are not recommended for use in children under 3 years of age. Geriatric Use: ADDERALL XRª has not been studied in the geriatric population.
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