Pharmacology Update

Methylphenidate Transdermal System (Daytrana™)

By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, 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 relationships to this field of study.

The FDA has approved the first transdermal patch for the treatment of attention deficit hyperactivity disorder (ADHD). This once daily methylphenidate patch is worn for nine hours and is designed to withstand normal daily activities including swimming and bathing. The patch is manufactured for Shire US Inc. by Noven Pharmaceuticals and is marketed as Daytrana™.

Indications

Methylphenidate transdermal system (MTS) is indicated for the treatment of ADHD in children 6 to 12 years of age.1

Dosage

The recommended dose of MTS is one 12.5 cm2 patch once daily which delivers 10 mg of drug. The patch should be applied to the hip area and worn for 9 hours. If the response is inadequate, the dose may be increased weekly to 18.75 cm2, 25 cm2, and 37.5 cm2. These deliver 15 mg, 20 mg, and 30 mg respectively.

MTS transdermal system is available in 4 strengths, delivery 10 mg, 15 mg, 20 mg, and 30 mg.

Potential Advantages

The patch provides a new delivery system for methylphenidate which allows for once-daily application.

Potential Disadvantages

The patch must be applied 2 hours before school and removed 9 hour later. MTS may be irritating to the skin and can cause an allergic skin rash. Skin sensitization has been reported in 13-22% of patients.2 The incidence of insomnia and anxiety may be higher with the patch than an oral extended-release formulation. Total drug exposure is higher with MTS compared to Concerta®, however this is mainly due to the 'inactive' enantiomer, l-methylphenidate.2

Comments

Daytrana™ is methylphenidate formulated in a multilayer transdermal system using Noven's DOT Matrix technology. The patch delivers methylphenidate comparable to immediate release oral methylphenidate given 3 times a day.3 The efficacy of the methylphenidate patch was shown in a phase II, double-blind, placebo-controlled, laboratory classroom assessment in children with ADHD.1,4 Subjects were optimized over 5 weeks using escalating doses then randomized to 1 week on the patch or placebo. The subjects were then crossed over to the opposite treatment the following week. Primary efficacy was measured with the Deportment subscale of the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Teacher Rating Scale. MTS showed significant improvement over a placebo patch from 2 to 12 hours after application. Adverse events, other than skin reactions, appeared similar to that expected with oral methylphenidate. The wear characteristics of the patch appear to be good with 90% of the patch surface adhered to the skin for most (86%) of the patches by the end of the classroom day.1,4 In a phase III study, MTS was compared to extended-release methylphenidate (Concerta®), and placebo in 270 subjects.5 The incidence of insomnia (13% vs 8%) and anorexia (26% vs 19%) seemed higher with MTS compared to Concerta®. There are currently no published comparison between MTP patch and an oral formulation. The efficacy of MTS and Concerta® appeared to be similar. The wholesale cost of MTS is $3.98 per day compared to $2.57-$2.95 for Concerta®.

Clinical Implications

Concern has been raised regarding ADHD drugs and the increased risk of sudden death, cardiovascular problems, and psychiatric problems (eg, psychosis, mania). In appears that emergency department visits for adverse events in patients on these drugs are not uncommon.6 In February 2006 the FDA's Drug Safety and Risk Management Advisory Committee recommended a "black-box" warning in the package insert.7 However the FDA Pediatric Advisory Committee recommended against such a warning in favor of "softer" cautionary language in the labeling.8

MTS patch provides an alternative to orally formulation for the treatment of ADHD. However, the safety of long-term use has not been established. The FDA's Psychopharmacologic Drug Advisory Committee recommend trying oral medications first.

References

1. Daytrana™ Product Information. Shire Pharmaceutical Inc, April 2006.

2. www.fda.gov/ohrms/dockets/ac/05/slides/2005-4195S1_01_FDA-Andreason.ppt. Accessed 5/26/06.

3. Pelham WE, et al. Transdermal methylphenidate, behavioral, and combined treatment for children with ADHD. Exp Clin Psychopharmacol. 2005;13:111-126.

4. McGough JJ, et al. A randomized, double-blind, placebo-controlled, laboratory classroom assessment of methylphenidate transdermal system in children with ADHD. J Atten Disord. 2006;9:476-485.

5. pn.psychiatryonline.org/cgi/content/full/41/1/1-a. Accessed 5/10/06.

6. Cohen AL, et al. Stimulant medications and attention deficit-hyperactivity disorder. N Engl J Med. 2006;354:
2294-2295.

7. www.medicalnewstoday.com/medicalnews.php?newsid=37631

8. www.psycport.com.