/publications/issue/2006/2006-08/2006-08-5753

Shire Pharmaceuticals' Daytrana

Author: Shire Pharmaceuticals' Daytrana

In April 2006, the FDA approved Shire's Daytrana (methylphenidate), the first and only transdermal treatment for attention deficit/hyperactivity disorder (ADHD). Daytrana should be used in conjunction with nonpharmacologic treatment.1,2

Pharmacology

Methylphenidate is classified as a central nervous system (CNS) stimulant and affects the CNS with minimal cardiovascular effects. The exact mechanism of methylphenidate is unknown, although it is thought to activate subcortical structures including the thalamus, the brainstem arousal system, and the cortex. This activation in turn produces a stimulatory effect. It has yet to be determined how methylphenidate exerts behavioral effects on children.1

Pharmacokinetics

Methylphenidate is a racemic mixture of d-and l-enantiomers, where d-enantiomer is considered the more pharmacologically active metabolite. The transdermal formulation bypasses first-pass metabolism, leading to increased exposure to d-methylphenidate (d-MPH). Compared with oral methylphenidate, a lower mg/kg dose of Daytrana is needed for higher d-MPH exposure.1

A phase 3 trial demonstrated the mean plasma peak concentrations of d- MPH as 39 ng/mL (range 0-114 ng/mL). The trial also determined an inversely proportional mean peak concentration of 25 ng/mL for 12 year olds (range 2- 80 ng/mL). For 6-year-olds, the mean peak concentration was 53 ng/mL (range 18-83 ng/mL).1 Lag time for Daytrana is an average of 3.1 hours (range 1-6 hours).

Clinical Trials

The efficacy of Daytrana was shown in a randomized, double-blind, doubledummy, multicenter, parallel-group, placebo- controlled study in children who were randomized in a 1:1:1 ratio to receive a methylphenidate patch, a matching placebo patch, an osmotically released oral system (OROS) methylphenidate tablet, or a matching placebo tablet.3

The study enrolled children aged 6 to 12 years who had been diagnosed with ADHD. Patients who showed at least a 25% reduction in scores on the ADHD rating scale (ADHD-RS) were maintained on their optimal dose for 2 weeks. Patients treated with the methylphenidate patch displayed statistically significant improvement on all 3 scales, compared with placebo.3

Safety

Common adverse events include insomnia, nervousness, loss of appetite, abdominal pain, weight loss, headache, tachycardia, aggressive behavior, and visual disturbances. Daytrana also may irritate the skin.1 Overdose symptoms include vomiting, agitation, tremors, hyperflexia, convulsions, euphoria, confusion, hallucinations, delirium, sweating, cardiac arrhythmias, and mydriasis.

Daytrana is contraindicated in patients with glaucoma, tics or a family history of Tourette's syndrome, hypersensitivity to methylphenidate, anxiety, tension, agitation, preexisting psychosis, seizures, or concomitant use of monoamine oxidase inhibitors. Daytrana is characterized as a pregnancy category C drug.

Dot Matrix Technology

Dot matrix technology includes a layer of acrylic that holds a large volume of drug. Silicone adhesive is used to keep the patch in place during everyday and rigorous activity, such as exercising and swimming.3,4 This technology creates an evenly dispersed drug patch and in turn provides reproducible blood levels of medications.

Daytrana is designed to release methylphenidate continuously. Once the patch is removed, residual methylphenidate remains under the skin and continues to be distributed. Therefore, methylphenidate plasma concentrations decline in a biexponential manner.1

Patch Instructions

The patch is applied on an alternating hip each day to a clean, dry area 2 hours before the effect is desired. It should be worn for a total of 9 hours (it may be removed earlier if a shorter duration of effect is desired).1 The patch should not be applied to open, cut, red, or irritated skin.

Methylphenidate release is increased if external heat is applied. Therefore, patients should be warned not to use heating pads or electric blankets while wearing a Daytrana patch. Daytrana is a Schedule II drug and may lead to dependence. Detailed patient information on patch application is included in the package insert.

Caryn Domenici, RPh, and Alka Patel, PharmD Ms. Domenici and Ms. Patel are both pharmacists at Brigham and Women's Hospital, Boston, Mass.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Rybovic, Pharmacy Times, Ascend Media Healthcare, 103 College Road East, Princeton, NJ 08540; or send an email request to: arybovic@ascendmedia.com.