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A closer look at new FDA actions: Shire's Vyavanse

Caryn Domenici, RPh, and Alka Patel, RPh, PharmD
Published Online: Saturday, September 1, 2007   [ Request Print ]

Shire?s Vyvanse

On February 23, 2007, the FDA approved Shire PLC?s lisdexamfetamine dimesylate (Vyvanse; formerly known as NRP 104) for the treatment of attention deficit/hyperactivity disorder (ADHD) in children 6 to 12 years of age.1 The US Drug Enforcement Agency classified Vyvanse as a schedule II controlled substance following recommendations from the FDA on May 3, 2007.1,2

Pharmacology

Vyvanse is the first approved prodrug stimulant. The reason for its development was that it provides a more consistent extended duration of effect and reduces the potential for abuse by eliminating alternative-route administration (intranasal, intravenous), as well as reducing the potential for overdose.2 Vyvanse is rapidly absorbed from the gastrointestinal tract and is converted into l-lysine, a natural amino acid, and dextroamphetamine, which is responsible for its activity.3

Dextroamphetamine is thought to block the reuptake of dopamine and norepinephrine. The mode by which amphetamines exert their therapeutic effect on ADHD is unknown. The conversion of Vyvanse to active dextroamphetamine is believed to occur via hepatic and/or first-pass intestinal metabolism. Vyvanse is not metabolized by CYP450 enzymes.

Approximately 96% of a 70-mg radioactive dose was found in the urine after administration to 6 healthy patients. The plasma elimination half-life of Vyvanse typically averaged less than 1 hour.3

Clinical Trials

A phase 3 randomized, multicenter, double-blind, placebo-controlled, forced-dose parallel-group study was conducted to assess the tolerability and efficacy of Vyvanse in school-aged children with ADHD, as compared with placebo.4 A total of 290 female and male children aged 6 to 12 years with ADHD were randomly assigned to receive Vyvanse 30 mg, 50 mg, and 70 mg with forced-dose titration or placebo once daily for 4 weeks. The ADHD Rating Scale Version-IV (ADHD-RS), the Conners? Parent Rating Scale-Revised (CPRS-R), and the Clinical Global Impression (CGI) of Improvement Scale were all used to evaluate efficacy.

The ADHD-RS total score from baseline to end point was improved by all groups, compared with placebo (P <.001). Using the CPRS-R scoring in the morning, afternoon, and evening, the parents/guardians of the Vyvanse group reported greater improvement in symptoms controlled throughout the day, compared with the parents/ guardians of patients who received placebo (P <.01). The greatest improvements were seen in the 70-mg group, compared with the placebo group, at all time points. The CGI ratings were either ?much improved? or ?very much improved? in =70% of the patients in the active-treatment groups, compared with 18% of the patients receiving placebo.4

Precautions/Contraindications

Vyvanse is contraindicated in patients with symptomatic cardiovascular disease, glaucoma, advanced arteriosclerosis, moderate-to-severe hypertension, or a known hypersensitivity to sympathomimetic amines. Patients who have agitated states or a history of drug abuse or were taking a monoamine-oxidase inhibitor within the past 14 days should not receive Vyvanse.3

It is recommended that growth be monitored in individuals taking Vyvanse. Clinical evaluation of tics, Tourette?s syndrome, and seizures should be performed before initiating Vyvanse, because these conditions may be exacerbated with the use of amphetamines.

The most common adverse effects seen with Vyvanse treatment are decreased appetite (39%) and insomnia (19%). Other adverse effects include headache, upper abdominal pain, irritability, nausea and vomiting, dry mouth, and dizziness.3

References

1. www.vyvanse.com/pressrelease.asp.

2. Vyvanse product information. Wayne, Pa: Shire Pharmaceuticals. May 2007.

3. Vyvanse package insert. Wayne, Pa: Shire US Inc. 2007.

4. Biederman J, Krishnan S, Zhang Y, McGough JJ, Findling RL. Efficacy and tolerability of lisdexamfetamine dimesylate (NRP104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study. Clinical Ther. 2007;29;450-463.

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