Dexmethylphenidate

The proposed mechanism of ADHD pharmacotherapy is to modulate neurotransmitters in order to improve academic and social functioning. Pharmacologic therapy can be divided into two categories stimulants and non-stimulants. Stimulant medications include methylphenidate, dexmethylphenidate, amphetamine salts, and dextroamphetamine, whereas non-stimulant medications include atomoxetine, tricyclic antidepressants (e.g., imipramine), clonidine, guanfacine, and bupropion. 

Dexmethylphenidate 5 mg every morning (children) T 5 mg/day in weekly 10-20 mg daily in the morning... 

Attention deficit hyperactivity disorder (ADHD) For the treatment of ADHD in patients 6 years of age and older. Dexmethylphenidate is indicated as an integral part of a total treatment program for ADHD that may include other measures (eg, psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all patients. Stimulants are not intended for use in the patient who exhibits symptoms secondary to environmental factors or other primary psychiatric disorders, including psychosis. 

The effectiveness of dexmethylphenidate for longer than 6 weeks has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use dexmethylphenidate for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient. 

Dexmethylphenidate extended-release capsules are for oral administration once daily in the morning. Capsules may be swallowed whole or alternatively may be administered by sprinkling the capsule contents on a small amount of applesauce. Individualize dosage according to the needs and responses of the patient. 

Patients new to methylphenidate The recommended starting dose of dexmethylphenidate for patients who are not currently taking racemic methylphenidate or for patients who are on stimulants other than methylphenidate is... 

Patients currently using methylphenidate For patients currently using methylphenidate, the recommended starting dose of dexmethylphenidate is half the dose of racemic methylphenidate. The maximum recommended dose is 20 mg/day (10 mg twice/day, immediate-release). 

Pharmacology Dexmethylphenidate hydrochloride is a CNS stimulant. It is the more pharmacologically active enantiomer of the d- and /-enantiomers and is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. Pharmacokinetics ... 

Absorption - Dexmethylphenidate hydrochloride is readily absorbed following oral administration. In patients with ADHD, plasma dexmethylphenidate concentrations increase rapidly, reaching a maximum in the fasted state at approximately 1 to 1.5 hours postdose. 

Distribution - Plasma dexmethylphenidate concentrations in children decline exponentially following oral administration. 

Metabolism - Dexmethylphenidate is metabolized primarily to c/- -phenyl-piperidine acetic acid (also known as c/-ritalinic acid) by de-esterification. This metabolite has little or no pharmacological activity. 

In vitro studies showed that dexmethylphenidate did not inhibit cytochrome P450 isoenzymes. 

Excretion - The mean plasma elimination half-life of dexmethylphenidate is approximately 2.2 hours. 

Fatigue Do not use dexmethylphenidate for the prevention or treatment of normal fatigue states. 

Seizures Methylphenidate may lower the convulsive threshold in patients with history of seizures, in patients with prior EEG abnormalities in the absence of a history of seizures, and, very rarely, in the absence of a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, discontinue the drug. Hypertension and other cardiovascular conditions Use cautiously in patients with hypertension. Monitor blood pressure at appropriate intervals in all patients taking dexmethylphenidate, especially those with hypertension. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate (eg, pre-existing hypertension, heart failure, recent Ml, hyperthyroidism). 

Lactation It is not known whether dexmethylphenidate is excreted in human milk. Children The safety and efficacy of dexmethylphenidate in children younger than 6 years of age have not been established. 

Drugs that may be affected by dexmethylphenidate or racemic methylphenidate include antihypertensive agents, pressor agents, coumarin anticoagulants, anticonvulsants, tricyclic antidepressants, selective serotonin reuptake inhibitors, and clonidine. 

Dexmethylphenidate may lower the seizure threshold in those with a history of seizures. 

Switching from immediate-release dexmethylphenidate (Focalin) Start Focalin XR at the same total daily dose as the Focalin dose. 

Dexmethylphenidate Focalin XR Capsule with 50% dexmethylphenidate dose as immediate-release beads and 50% as delayed-release beads... 

Adderall XR (package insert). Wayne, PA, Shire US Inc, 2004 Angrist B, d Hollosy M, Sanfilipo M, et al Central nervous system stimulants as symptomatic treatments for AIDS-related neuropsychiatric impairment. J Clin Psychophamiacol 12 268—272, 1992 Arnold LE, Lindsay RL, Connors CK, et al A douhle-hlind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention-deficit hyperactivity disorder. I Am Acad Child Adolesc Psychiatry 14 542—554, 2004 Belle DJ, Ernest CS, Sauer JM, et al Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. I Clin Pharmacol 42 1219-1227, 2002... 

McGough JJ, Pataki CS, Suddath R Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder. Expert Rev Neu-rother 5 437 41, 2005b... 

Wigal S, Swanson JM, Feifel D, et al A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and tf,/-iArco-methylpheni-date hydrochloride in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 43 1406-1414, 2004 Wilens TE, Biederman J The stimulants. Psychiatr Clin North Am 15 191-222, 1992... 

PS,PS)-2-Phenyl-2-(piperidin-2-yl)acetic acid methyl ester (INN methyl-phenidate) is a centrally acting sympathomimetic used in the treatment of attention-deficit/hyperactivity disorder in children. Dexmethylphenidate is the pure (and significantly more active) enantiomer with the R,R configuration available in the USA. The diastereomeric racemate with the RS,SR configuration whilst a commercially available chemical is not used as a pharmaceutical. (Note the small structural difference between these compounds and levofacetoperane, question 149). 

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