Out Of The Pipeline

Transdermal methylphenidate

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Patch designed for flexible, long-acting coverage.


 

References

When prescribing methylphenidate to children with attention-deficit/hyperactivity disorder (ADHD), psychiatrists have had two options:

  • immediate-release oral methylphenidate, which works for 3 to 5 hours, necessitating multiple daily doses
  • extended-release oral methylphenidate, which can prevent irritability and other rebound symptoms caused by multiple daily dosing.1 Because its effects last 12 hours, however, once-daily dosing with this formulation is inflexible.

A new option—a transdermal methylphenidate patch FDA-approved for treating ADHD in children ages 6 to 12 (Table 1)—offers flexible methylphenidate coverage based on response to or need for the medication.

Table 1

Transdermal methylphenidate: Fast facts

Brand name: Daytrana
Class: CNS stimulant
FDA-approved indication: ADHD in children ages 6 to 12
Manufacturer: Noven Pharmaceuticals (marketed by Shire PLC)
Dosing forms: 10-, 15-, 20-, and 30-mg patches
Recommended dosage: One 10- to 30-mg patch daily, worn on the hip for 9 hours. Patient can remove patch sooner if side effects become problematic.

Clinical implications

The transdermal patch allows dosing to be tailored—or changed day to day as needed—to maximize effectiveness and reduce side-effect risk. The manufacturer recommends that the patch be worn for 9 hours daily, but it can be removed sooner if children experience appetite loss, insomnia, or other adverse effects with 9 hours of exposure to methylphenidate.

Minimizing daily exposure to methylphenidate can also reduce the risk of long-term effects. Findings from one large, randomized clinical trial2 suggest that chronic exposure to high-dose stimulant medications might suppress growth in height and weight, although other data indicate that initial height reductions found in children receiving methylphenidate for ADHD were no longer significant in adulthood.3

The patch also could benefit youths who have trouble following dosing schedules and young children who are unable to swallow pills.

How it works

The patch contains methylphenidate dispersed in an acrylic multipolymeric adhesive that is further dispersed in a silicone adhesive.4 The methylphenidate within the acrylic adhesive flows into the skin, then into the bloodstream. The patch is worn on the hip—where it is covered by clothing and unlikely to be dislodged—and changed daily.

The patch comes in four sizes—12.5, 18.75, 25, and 37.5 cm2—which, respectively, deliver 10, 15, 20, and 30 mg of methylphenidate over 9 hours.4 Methylphenidate concentration is the same for all four sizes, so patch size and duration of use determine dose delivery.

In clinical trials, therapeutic effect was seen 2 hours after patch placement and continued through 12 hours.5 Methylphenidate is delivered continuously while the patch is in place and for as long as 2 hours after it is removed.

Pharmacokinetics

Methylphenidate, a known CNS stimulant, blocks norepinephrine and dopamine reuptake in the presynaptic neuron, thereby releasing more of these neuro-transmitters into the extraneuronal space.4 Methylphenidate’s precise therapeutic action in ADHD is not known.

Methylphenidate is a racemic mixture of d- and l-enantiomers, the first of which is believed to be more active. Whereas the liver removes the l-enantiomer from oral methylphenidate, the transdermal formulation bypasses the liver and preserves the l-enantiomer, thus increasing exposure to racemic methylphenidate. This means that optimal dosages of transdermal methylphenidate (10 to 30 mg/d) may be lower compared with the oral formulation5-7 (Table 2).

Methylphenidate’s d-enantiomer has a mean 3- to 4-hour elimination half-life, approximately twice that of the l-enantiomer. This is why transdermal methylphenidate continues to exert therapeutic effect several hours after the patch is removed.5

Table 2

Transdermal methylphenidate dosage delivery in children ages 6 to 12

Dose delivered over 9 hours (mg)Patch size (cm2)Dosage rate (mg/hr)Methylphenidate content per patch (mg)
1012.51.127.5
1518.751.641.3
20252.255.0
3037.53.382.5
Source: Reference 4

Efficacy

Results from randomized, double-blind, placebo-controlled trials support short-term use of transdermal methylphenidate in ADHD. The following studies recruited children ages 6 to 12 with the disorder.

Dose-ranging study. Thirty-three children participating in a summer treatment program received transdermal methylphenidate, 6.25, 12.5, or 25 cm2 12 hours daily for 8 days.6 All three patch sizes were associated with improved academic, social, and behavioral functioning based on a range of measures.

Dose response rate diminished with higher dosages, and significant further improvements were difficult to detect as dosages increased. The children also received intensive behavioral treatment during the study, which might have accounted for some therapeutic gains and diminished the researchers’ ability to detect subtle improvements with increased dosages.

Children also had fewer negative behaviors during the first hour when the patch was applied at 6 AM instead of 7 AM. This suggests that the patch might produce optimal effect when placed first thing in the morning.

Randomized crossover trial.7 Across 6 weeks, 27 children were given placebo or transdermal methylphenidate, 12.5, 25, or 37.5 cm2/d. The children also received behavior modification treatment on alternating weeks. Medication was randomly assigned and varied daily for 4 days per week over 6 weeks, and behavioral treatment was varied weekly for 4 weeks. Each subject took each dosage for 2 days without behavioral treatment and for 4 days with behavioral treatment.

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