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Lisdexamfetamine Dimesylate Capsule (Vyvanse™) CII
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
A prodrug of dextroamphetamine has been approved by the FDA for the treatment of attention-deficit/hyperactivity disorder (ADHD). Lisdexamfetamine is the d-amphetamine covalently bound to l-lysine. It is marketed by Shire US Inc as Vyvanse.
Lisdexamfetamine is approved for the treatment of ADHD in children 6-12 years of age.1
The recommended starting dose in children (6-12 years of age) is 30 mg once daily in the morning. The dose may be increased to 70 mg daily if clinically appropriate. The dose should be increased in increments of 20 mg at weekly intervals. Doses greater than 70 mg are not recommended.1 The capsule may be swallowed whole or the contents dissolved in water and taken without regard to meals.
Lisdexamfetamine is supplied as 30 mg, 50 mg, and 70 mg capsules.
Lisdexamfetamine is a prodrug that provides a gradual release of d-amphetamine and may reduce abuse potential.2,3
The drug shares the same warnings as amphetamine (eg, abuse potential, dependence, sudden death and cardiovascular risks).1 Lisdexamfetamine has not been studied in children older than 12.
Lisdexamfetamine is the latest drug approved for the treatment of ADHD. It is not a new chemical entity but a prodrug for d-amphetamine. Its efficacy was shown in two double-blind, placebo-controlled studies in children ages 6-12 years. In the first study, subjects were randomized to 30 mg, 50 mg, or 70 mg for 4 weeks (N = 290). The primary endpoint was the change from baseline in the ADHD rating scale (AHDD-RS) total score. Reductions from baseline were 21.8, 23.4, and 26.7 vs 6.2 points for 30 mg, 50 mg, 70 mg and placebo respectively.1,2 These represented a 50% to 60% reduction for lisdexamfetamine to about 15% for placebo. The response rates (30% or greater decrease in ADHD-RS total score) were 66%, 72%, 77%, and 18% respectively. In the second study (n = 52), subjects were randomized to lisdexamfetamine (30 mg, 50 mg, 70 mg), placebo, or continued Adderall XR treatment after a 3-week open label dose titration with Adderall XL.1 Lisdexamfetamine was reported to be significantly better than placebo and similar to Adderall XR. Lisdexamfetamine gradually releases dextroamphetamine via rate limiting hydrolysis of the lysine group. The systemic exposure of dextroamphetamine over the first 4 hours is about 2/3rd that for a comparable amounts of dextroamphetamine.2,3
In a study to assess abuse potential, lisdexamfetamine 50 mg and 100 mg were not significantly different from placebo in adult stimulant abusers (n = 36) in terms of likability (Drug Rating Questionnaire-Subject Liking scale)3. However the 150 mg dose, d-amphetamine (40 mg), and diethypropion (200 mg) was significantly greater than placebo.3 Adverse events for lisdexamfetamine are similar to those for d-amphetamine (decrease appetite, insomnia, irritability, decreased weight, and dizziness).3 Lisdexamfetamine is priced the same for all strengths and is the same as Adderall XR, $3.41 per day (both distributed by Shire). Lisdexamfetamine 50 mg tablets and dextroamphetamine sulfate 20 mg contains about the same amount of amphetamine base.3
It's not clear if lisdexamfetamine offers any significant clinical advantage over other ADHD drugs in general or specifically over d-amphetamine. The possibility of reduced abuse potential is interesting and may be dose dependent. Still, the drug's clinical relevance remains to be established.
1. Vyvanse Product Information. Shire US Inc., February 2007.
2. Jasinswki D, et al. US Psychiatric and Mental Health Congress: 2006 Nov 17; New Orleans (LA).
3. Blick SKA and Keating, GM. Pediatr Drugs. 2007;9(2):129 -35.