In a prenatal and postnatal development study where rats were treated with transdermal selegiline at doses approximately 8, 24, and 60 times the MRHD on days 6 to 21 of gestation and days 1 to 21 of the lactation period, concentrations of selegiline and its metabolites in milk were approximately 15 and 5 times, respectively, the concentrations in maternal plasma.
Use of EMSAM in patients less than 12 years of age is contraindicated because of the potential for a hypertensive crisis [see Contraindications (4)].
Limited pharmacokinetic data with doses lower than in the commercially available formulations suggest that children under age 12 may be exposed to increased levels of selegiline compared to adolescents and adults, administered with and without dietary modifications, therefore, there may be an increased risk of hypertensive crisis, even at the lowest dose of EMSAM.
Efficacy has not been established in pediatric patients ages 12 to 17 years with MDD and EMSAM is not recommended for use in this age range [see Clinical Pharmacology (12.3)].
A multi-center, randomized, double-blind, placebo-controlled, flexible-dose trial in 308 adolescents (ages 12 to 17 years) with MDD failed to demonstrate the efficacy of EMSAM. Diagnosis of major depressive disorder (single episode or recurrent, moderate to severe) was based on according DSM-IV criteria and Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS). Enrolled patients had a Children's Depression Rating Scale-Revised of ≥ 45 at the screening visit. Trial participants were randomized 1:1 to either EMSAM or matching placebo without forced titration for a period of 12 weeks. Active treatment consisted of EMSAM transdermal system at a dose of 6 mg per 24 hours, 9 mg per 24 hours, or 12 mg per 24 hours. The primary efficacy endpoint was the difference in total score on the Children's Depression Rating Scale-Revised (CDRS-R) from baseline to the end of study (EOS) (Week 12). There was no observed difference in effect on CDRS-R Total Score at Week 12 (EOS) between treatments. The mean reduction in CDRS-R Total Score was 21.4 in the EMSAM-treated subjects and 21.5 in those receiving placebo treatment. Safety endpoints included physical examination, 12-lead electrocardiogram, respiration rate, temperature, supine and standing blood pressure and heart rate, application site assessments, and adverse events. Overall, safety findings were similar to those observed in EMSAM trials conducted in adults. Treatment-emergent adverse events reported by at least 5% of EMSAM-treated patients at a rate at least twice the placebo rate were insomnia (6%, 3%) and upper respiratory tract infection (7%, 3%).