• DOI:10.2165/11201140-000000000-00000
• Corpus ID: 24975170

Dexmethylphenidate Extended Release

@article{Moen2009DexmethylphenidateER,
  title={Dexmethylphenidate Extended Release},
  author={Marit D. Moen and Susan J. Keam},
  journal={CNS Drugs},
  year={2009},
  volume={23},
  pages={1057-1083}
}

• Marit D. Moen, S. Keam
• Published 1 December 2009
• Medicine
• CNS Drugs

SummaryAbstractDexmethylphenidate extended release (XR) [Focalin® XR] is a CNS stimulant indicated for the treatment of attention-deficit hyperactivity disorder (ADHD) in patients aged ≥6 years. Dexmethylphenidate contains the d-threo- enantiomer of methylphenidate. Dexmethylphenidate XR capsules have a bimodal release profile, which mimics two doses of dexmethylphenidate immediate release (IR) given 4 hours apart, and allows once-daily administration.Once-daily dexmethylphenidate XR was effective and generally well tolerated in the treatment of ADHD in children, adolescents and adults in placebocontrolled trials. Improvements in ADHD symptoms were significantly greater for dexmethylphenidate XR versus placebo throughout the day, from as early as 0.5 hours after drug administration up to 11–12 hours after administration. Furthermore, dexmethylphenidate XR showed greater efficacy than osmotic release oral system (OROS®) methylphenidate over the first half of the laboratory classroom day in crossover trials; however, assessments late in the day (10–12 hours post-dose) favoured OROS® methylphenidate. The once-daily administration regimen with dexmethylphenidate XR avoids the need for a midday dose to be administered at school; administration options are extended in that the contents of the dexmethylphenidate XR capsule can be sprinkled on apple sauce for patients unable to swallow the capsule whole. Although dexmethylphenidate XR is a controlled substance in the US, this formulation appears to have a low risk of abuse or misuse. Thus, dexmethylphenidate XR extends the range of first-line pharmacological treatment options for children, adolescents or adults with ADHD, particularly for patients who require a rapid onset and prolonged duration of action, including children who require a reduction in ADHD symptoms throughout the school day.Pharmacological PropertiesMethylphenidate is thought to increase levels of dopamine and noradrenaline (norepinephrine) in the synaptic cleft in specific regions of the brain, primarily by blocking their reuptake into presynaptic neurons. However, the neurophysiology of ADHD is not fully understood. Dexmethylphenidate contains only the d-threo- enantiomer of methylphenidate, which is primarily responsible for the beneficial effects of racemic methylphenidate. The l-enantiomer appears to have negligible activity.Oral dexmethylphenidate XR capsules have a bimodal pharmacokinetic profile because each capsule contains half the dexmethylphenidate dose as immediaterelease beads and half as enteric-coated, delayed-release beads. Following a single dose of oral dexmethylphenidate XR, the first dexmethylphenidate peak plasma concentration is reached at 1.5 hours, and a second peak is reached at 6.5 hours after drug administration. A single dose of dexmethylphenidate XR 20 mg is bioequivalent to two doses of dexmethylphenidate IR 10 mg given 4 hours apart. Bioequivalence of a similar type of extended-release formulation of methylphenidate administered as a whole capsule or as the capsule contents sprinkled on apple sauce has been established, and this is expected to also apply to dexmethylphenidate XR capsules.Therapeutic EfficacyThe efficacy of oral dexmethylphenidate XR in children (aged 6–12 years) with ADHD was evaluated in five randomized, double-blind, crossover, placebocontrolled, multicentre trials conducted in a laboratory classroom setting. Improvements in ADHD symptoms, measured by changes in Swanson, Kotkin, Agler, M-Flynn and Pelham Rating Scale (SKAMP)-Combined scores from pre-dose, were significantly greater for dexmethylphenidate XR versus placebo at all primary endpoint post-dose assessment timepoints between 0.5 and 12 hours after study drug administration, and most post-dose secondary timepoint assessments.Furthermore, the improvement in SKAMP-Combined score from pre-dose was significantly greater with dexmethylphenidate XR (20 or 30mg/day) than with OROS® methylphenidate (36 or 54mg/day) 2 hours after administration of study medication. Significantly greater improvements in ADHD symptoms were seen for dexmethylphenidate XR versus OROS® methylphenidate early in the day (0.5–5 hours after drug administration), whereas improvements with OROS® methylphenidate were significantly greater than those with dexmethylphenidate XR at 10–12 hours after drug administration.In a 7-week, double-blind, parallel-group study in children and adolescents (aged 6–17 years), and a 5-week, double-blind, parallel-group study in children (aged 6–12 years), the improvement in Conners’ ADHD/DSM-IV Scale-Teacher (CADS-T) total subscale scores from baseline to the final visit was significantly greater for dexmethylphenidate XR versus placebo.Adult dexmethylphenidate XR recipients experienced a significantly greater improvement in ADHD symptoms than placebo recipients, as measured by the change in DSM-IV ADHD-Rating Scale (ADHD-RS) total scores from baseline to the end of a 5-week, randomized, double-blind, parallel-group study. There appeared to be further improvements in ADHD-RS scores during a 6-month noncomparative extension phase.TolerabilityOral dexmethylphenidate XR was generally well tolerated in clinical studies in patients with ADHD, with most adverse events being of mild or moderate severity. The most common treatment-emergent adverse events reported with dexmethylphenidate XR 20 mg once daily in randomized, double-blind placebocontrolled trials in children (5 weeks’ duration), children and adolescents (7 weeks’ duration) and adults (5 weeks’ duration) with ADHD were headache, decreased appetite, upper abdominal pain (children) and insomnia (adults). The adverse events profile of dexmethylphenidate XR in five crossover trials in children with ADHD was consistent with that seen in the parallel-group trials in children, and the adverse events profile of dexmethylphenidate XR in the noncomparative, 6-month extension phase of the trial in adults with ADHD was consistent with that seen in the double-blind phase.There were no clinically significant changes in vital signs for patients receiving dexmethylphenidate XR in clinical studies. Mean changes in bodyweight for dexmethylphenidate XR versus placebo were −0.5 kg versus 0.4 kg in the 7-week study in children and adolescents, and −1.4, −1.2 and −1.7 kg for dexmethylphenidate XR 20, 30 and 40mg/day, respectively, versus −0.1 kg for placebo in the 5-week study in adults.