Although the primary mechanism of methylphenidate is not known, its effects appear to be mediated by blockage of the reuptake mechanism of dopaminergic neurons.

ALERT: U.S. Boxed Warning

The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.

U.S. Brand Names

Concerta®; Daytrana®; Metadate CD®; Metadate® ER; Methylin®; Methylin® ER; Ritalin LA®; Ritalin-SR®; Ritalin®

Medication Safety Issues

Sound-alike/look-alike issues:

Metadate CD® may be confused with Metadate® ER

Metadate® ER may be confused with Metadate CD®, methadone

Methylphenidate may be confused with methadone

Ritalin® may be confused with Ismelin®, Rifadin®, ritodrine

Ritalin LA® may be confused with Ritalin-SR®

Ritalin-SR® may be confused with Ritalin LA®

Canadian Brand Names

Apo-Methylphenidate®; Apo-Methylphenidate® SR; Biphentin®; Concerta®; Novo-Methylphenidate ER-C; PHL-Methylphenidate; PMS-Methylphenidate; ratio-Methylphenidate; Ritalin®; Ritalin® SR; Sandoz-Methylphenidate SR

Therapeutic Category

Central Nervous System Stimulant

Dosing: Usual

(For additional information see "Methylphenidate: Drug information")

Note: Discontinue medication if no improvement is seen after appropriate dosage adjustment over a one-month period of time:

Oral:

Immediate release product (Methylin®, Ritalin®):

Children ≥6 years: ADHD: Initial: 0.3 mg/kg/dose or 2.5-5 mg/dose given before breakfast and lunch; increase by 0.1 mg/kg/dose or by 5-10 mg/day at weekly intervals; usual dose: 0.3-1 mg/kg/day; maximum dose: 2 mg/kg/day or 60 mg/day; specific patients may require 3 doses/day (ie, additional dose at 4 PM)

Adults: Narcolepsy: 10 mg 2-3 times/day; maximum dose: 60 mg/day

Metadate® ER, Methylin® ER, Ritalin-SR®: Children ≥6 years and Adults: Sustained release and extended release tablets (duration of action ∼8 hours) may be given in place of regular tablets, once the daily dose is titrated using the regular tablets and the titrated 8-hour dosage corresponds to sustained release tablet size

Concerta®:

Methylphenidate-naive patients: Initial: Concerta® dose:

Children ≥6 years and Adolescents: 18 mg once daily

Adults: 18-36 mg once daily

Patients currently using methylphenidate: Children ≥6 years and Adults: Note: Initial dose: Dosing based on current regimen and clinical judgment; suggested dosing listed below:

Switching from methylphenidate immediate release 5 mg 2-3 times/day: Concerta® 18 mg once daily

Switching from methylphenidate immediate release 10 mg 2-3 times/day: Concerta® 36 mg once daily

Switching from methylphenidate immediate release 15 mg 2-3 times/day: Concerta® 54 mg once daily

Switching from methylphenidate immediate release 20 mg 2-3 times/day: Concerta® 72 mg once daily

Dosage adjustment: May increase by 18 mg/day increments at weekly intervals

Maximum dose:

Children 6-12 years: 54 mg/day

Adolescent and Adults: 72 mg/day; do not exceed 2 mg/kg/day

Metadate CD®: Children ≥6 years and Adults: Initial: 20 mg once daily; may increase by 20 mg/day increments at weekly intervals; maximum dose: 60 mg once daily

Ritalin LA®: Children ≥6 years and Adults:

Methylphenidate naive patients: Initial: 20 mg once daily; may increase by 10 mg/day increments at weekly intervals; maximum dose: 60 mg once daily; Note: If a lower initial dose is desired, patients may begin with Ritalin LA® 10 mg once daily. Alternatively, patients may begin therapy with an immediate release product, and switch to Ritalin LA® once immediate release dosage is titrated to 5 mg twice daily (see below)

Patients currently receiving methylphenidate: Initial dose: See table; may increase by 10 mg/day increments at weekly intervals; maximum dose: 60 mg once daily

Generic Equivalent Available: U.S.

Yes: Immediate release tablet, oral solution, sustained release tablet

Administration

Oral: Immediate and sustained release tablets: Administer on an empty stomach ∼30-45 minutes before meals; do not crush, chew, or break sustained or extended release dosage form, swallow whole; to avoid insomnia, last daily dose should be administered several hours before retiring.

Concerta®: May be administered without regard to food, but must be taken with water, milk, or juice; administer dose once daily in the morning; do not crush, chew, or divide tablets

Metadate CD®: Administer dose once daily in the morning, before breakfast, with water, milk, or juice; capsule may be swallowed whole or opened and contents sprinkled on a small amount (one tablespoonful) of applesauce; immediately consume drug/applesauce mixture; do not store for future use; drink fluids after consuming drug/applesauce mixture to ensure complete swallowing of beads; do not crush, chew, or divide capsules or its contents

Methylin® chewable tablet: Children and Adults: Administer with at least 8 ounces of water or other fluid (choking may occur if not enough fluids are taken)

Ritalin LA®: Administer dose once daily in the morning; may be administered with or without food (but some food may delay absorption); capsule may be swallowed whole or may be opened and contents sprinkled on a small amount (one spoonful) of applesauce (Note: Applesauce should not be warm); immediately consume drug/applesauce mixture; do not store for future use; do not crush, chew, or divide capsule or its contents

Topical: Transdermal (Daytrana™): Apply patch immediately after opening pouch and removing protective liner; do not use patch if pouch seal is broken; do not cut patch; do not use patches that are cut or damaged. If difficulty is experienced when separating the patch from the liner or if any medication (sticky substance) remains on the liner after separation, discard that patch and apply a new patch. Apply to clean, dry, healthy skin on the hip; do not apply to oily, damaged, or irritated skin; do not apply to the waistline; do not premedicate the patch site with hydrocortisone or other solutions, creams, ointments, or emollients. Apply at the same time each day, 2 hours before effect is needed. Alternate site of application daily (ie, use alternate hip). Press patch firmly for 30 seconds to ensure proper adherence. Remove patch 9 hours after application. Patch may be removed earlier if a shorter duration of action is required or if late day adverse effects occur.

Avoid exposure of application site to external heat source (eg, hair dryers, electric blankets, heating pads, heated water beds), which may significantly increase the rate and amount of drug absorbed. Exposure of patch to water during swimming, bathing, or showering may affect patch adherence. Do not reapply patch with dressings, tape, or other adhesives. If patch should become dislodged, may replace with new patch (to different site) but total wear time should not exceed 9 hours.

During removal, peel off patch slowly. If needed, patch removal may be helped by applying an oil-based product (ie, mineral oil, olive oil, or petroleum jelly) to the patch edges, gently working it underneath the patch edges. If a patch is not able to be removed, contact a physician or pharmacist. Nonmedical adhesive removers and acetone-based products, such as nail polish remover, should not be used to remove patches or adhesive. If adhesive residue remains on child’s skin after patch removal, use an oil-based product and gently rub area to remove adhesive. Avoid touching the sticky side of the patch. Wash hands with soap and water after handling.

Dispose of used patch by folding adhesive side onto itself, and discard in toilet or appropriate lidded container; discard unused patches that are no longer needed in the same manner; protective pouch and liner should be discarded in an appropriate lidded container. Note: Used patches contain residual drug; keep all transdermal patches out of the reach of children.

Use

Oral:

Concerta®: Treatment of attention-deficit/hyperactivity disorder (ADHD) (FDA approved in ages 6-65 years)

Ritalin LA®: Treatment of ADHD (FDA approved in ages 6-12 years)

Metadate CD®: Treatment of ADHD (FDA approved in ages 6-15 years)

Metadate® ER, Methylin®, Methylin ER®, Ritalin®, Ritalin SR®: Treatment of ADHD, narcolepsy (FDA approved in ages ≥6 years and adults)

Topical Patch: Daytrana™: Treatment of ADHD (FDA approved in ages 6-17 years)

Adverse Reactions

Cardiovascular: Cardiac arrhythmias; cerebral arteritis; cerebral occlusion (case reports); hypertension; hypotension; palpitations; serious cardiovascular events, including sudden death in patients with pre-existing structural cardiac abnormalities or other serious heart problems; tachycardia

Central nervous system: Aggression, dizziness, drowsiness, emotional lability, fever, headache, insomnia, irritability, movement disorders, motor tics, nervousness, neuroleptic malignant syndrome (very rare and usually in patients receiving medications associated with the syndrome; one case with concurrent first dose of venlafaxine has been reported), precipitation of Tourette's syndrome, seizure, toxic psychosis (rare), transient depression

Dermatologic: Erythema multiforme, exfoliative dermatitis, necrotizing vasculitis, rash, scalp hair loss

Endocrine & metabolic: Growth suppression, weight loss

Gastrointestinal: Abdominal pain, anorexia, diarrhea, nausea, potential for GI obstruction with Concerta®, vomiting

Hematologic: Anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura

Hepatic: Abnormal liver function, hepatic coma, transaminases increased

Local: Transdermal system: Allergic contact dermatitis, application site reactions, edema, erythema, itching, papules, vesicles

Neuromuscular & skeletal: Arthralgia, dyskinesia

Ocular: Blurred vision, problems with accommodation, visual disturbances

Respiratory: Cough, oropharyngeal pain (Concerta®)

Miscellaneous: Physical and psychological dependence

<1%, postmarketing, and/or case reports: Alkaline phosphatase increased, angina pectoris, bradycardia, chest pain, diplopia, disorientation, erythema, extrasystole, hallucinations, hypersensitivity reactions (eg, anaphylactic reactions, angioedema, auricular swelling, bullous conditions, eruptions, exanthemas, pruritus, rash, urticaria), mania, migraine, muscle twitching, mydriasis, obsessive-compulsive disorder, supraventricular tachycardia, ventricular extrasystole

Contraindications

Hypersensitivity to methylphenidate or any component; glaucoma; motor tics; Tourette's syndrome (diagnosis or family history); patients with marked agitation, tension, and anxiety; use with or within 14 days following MAO inhibitor therapy (hypertensive crisis may occur)

Metadate CD® and Metadate ER® are also contraindicated in patients with severe hypertension, heart failure, arrhythmia, hyperthyroidism, thyrotoxicosis, recent MI, or angina.

Precautions

Use with caution in patients with heart failure, recent MI, hyperthyroidism, seizures, acute stress reactions, emotional instability. Hematological monitoring is advised with long term use. Stimulants like methylphenidate have a demonstrated value as part of a comprehensive treatment program for ADHD.

Chewable tablets contain aspartame which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria. Chewable tablets must be taken with adequate amount of liquid, otherwise tablet may swell and block the throat or esophagus and cause choking; do not use chewable tablets in patients who have difficulty swallowing; instruct patients to seek immediate medical attention if chest pain, vomiting, difficulty in breathing or swallowing occur after taking chewable tablet.

Metadate CD® contains sucrose; avoid use in hereditary problems of fructose intolerance, sucrase-isomaltose insufficiency, and glucose-galactose malabsorption. Metadate® ER contains lactose; avoid in hereditary problems of galactose intolerance, glucose-galactose malabsorption, and the Lapp lactase deficiency. Avoid concomitant use of Metadate® CD or Metadate® ER with halogenated anesthetics; use may cause sudden elevations in blood pressure; if surgery is planned, do not administer Metadate® CD or Metadate® ER on the day of surgery.

Warnings

Serious cardiovascular events including sudden death may occur in patients with pre-existing structural cardiac abnormalities or other serious heart problems. Sudden death has been reported in children and adolescents; sudden death, stroke, and MI have been reported in adults. Avoid the use of CNS stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems that could place patients at an increased risk to the sympathomimetic effects of CNS stimulants. Patients should be carefully evaluated for cardiac disease prior to initiation of therapy. Note: The American Heart Association recommends that all children diagnosed with ADHD who may be candidates for medication, such as methylphenidate, should have a thorough cardiovascular assessment prior to initiation of therapy. This assessment should include a combination of medical history, family history, and physical examination focusing on cardiovascular disease risk factors. An ECG is not mandatory but should be considered. Note: In a recent retrospective study on the possible association between stimulant medication use and sudden death in children, 564 previously healthy children who died suddenly in motor vehicle accidents were compared to a group of 564 previously healthy children who died suddenly. Two of the 564 (0.4%) children in motor vehicle accidents were taking stimulant medications compared to 10 of 564 (1.8%) children who died suddenly. While the authors of this study conclude there may be an association between stimulant use and sudden death in children, there were a number of limitations to the study and the FDA cannot conclude this information impacts the overall risk:benefit profile of these medications (Gould, 2009). If a child displays symptoms of cardiovascular disease, including chest pain, dyspnea, or fainting, parents should seek immediate medical care for the child. Note: ECG abnormalities and 4 cases of sudden cardiac death have been reported in children receiving clonidine with methylphenidate; reduce dose of methylphenidate by 40% when used concurrently with clonidine; consider ECG monitoring.

Stimulant medications may increase blood pressure (average increase 2-4 mm Hg) and heart rate (average increase 3-6 bpm); some patients may experience greater increases; use stimulant medications with caution in patients with hypertension and other cardiovascular conditions that may be exacerbated by increases in blood pressure or heart rate. Psychiatric adverse events may occur. Stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychosis. New-onset psychosis or mania may occur with stimulant use. May induce mixed/manic episode in patients with bipolar disorder. May be associated with aggressive behavior or hostility (monitor for development or worsening of these behaviors).

Safety and efficacy have not been established in children <6 years of age (use is not recommended in children <6 years of age). Long-term effects in pediatric patients have not been determined. Use of stimulants in children has been associated with growth suppression (monitor growth; treatment interruption may be needed). Appetite suppression may occur; monitor weight during therapy, particularly in children. Stimulants may lower seizure threshold leading to new onset or breakthrough seizure activity (use with caution in patients with a history of seizure disorder). Visual disturbances (difficulty in accommodation and blurred vision) have been reported.

CNS stimulants possess a high potential for abuse; misuse may cause sudden death and serious cardiovascular adverse events; prolonged administration may lead to drug dependence; abrupt discontinuation following high doses or for prolonged periods may result in symptoms of withdrawal; avoid abrupt discontinuation in patients who have received methylphenidate for prolonged periods; use with caution in patients with history of ethanol or drug abuse. Do not use for severe depression or normal fatigue states.

A potential for GI obstruction exists with Concerta® (tablet is nondeformable); do not ordinarily use in patients with severe GI narrowing (eg, esophageal motility disorders, small bowel inflammatory disease, short gut syndrome, history of cystic fibrosis, peritonitis, chronic intestinal pseudo-obstruction, or Meckel's diverticulum). Transdermal system may cause allergic contact sensitization, characterized by intense local reactions (edema, vesicles, papules) that may spread beyond the patch site; remove patch and monitor application site if reaction occurs; seek further evaluation if erythema, edema, and/or papules do not significantly decrease or resolve within 24 hours of patch removal. Allergic sensitization may subsequently manifest systemically when methylphenidate is administered orally or via other routes; systemic sensitization reactions may include dermatitis, generalized skin eruptions, headache, fever, vomiting, diarrhea, arthralgia, or malaise; initiate oral methylphenidate under close medical supervision in patients who have experienced a contact sensitization to the transdermal system; some of these patients may not be able to take methylphenidate in any dosage form. Do not expose transdermal application site to direct external heat sources (eg, electric blankets, heating pads, heated water beds), a >2-fold increase in drug release may occur.

Controlled Substance

C-II

Medication Guide

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Concerta®: file://www.fda.gov/downloads/Drugs/DrugSafety/ucm088575.pdf

Daytrana™: file://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021514s009s010MedGuide.pdf

Metadate CD®: file://www.fda.gov/downloads/Drugs/DrugSafety/ucm088635.pdf

Methylin® chewable tablet: file://www.fda.gov/downloads/Drugs/DrugSafety/ucm088639.pdf

Methylin® oral solution: file://www.fda.gov/downloads/Drugs/DrugSafety/ucm088640.pdf

Ritalin®: file://www.fda.gov/downloads/Drugs/DrugSafety/ucm089090.pdf

Ritalin LA®: file://www.fda.gov/downloads/Drugs/DrugSafety/ucm089092.pdf

Ritalin-SR®: file://www.fda.gov/downloads/Drugs/DrugSafety/ucm089826.pdf

Metabolism/Transport Effects

Inhibits CYP2D6 (weak)

Drug Interactions

(For additional information: Launch Lexi-Interact™ Drug Interactions Program )

Antacids: May increase the absorption of Methylphenidate. Specifically, antacids may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy

Antihypertensives: Methylphenidate may diminish the antihypertensive effect of Antihypertensives. Exceptions: Minoxidil (Topical). Risk C: Monitor therapy

Anti-Parkinson's Agents (Dopamine Agonist): Methylphenidate may enhance the adverse/toxic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy

Antipsychotics: May enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotics. Risk C: Monitor therapy

Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

CloNIDine: Methylphenidate may enhance the adverse/toxic effect of CloNIDine. Risk C: Monitor therapy

Fosphenytoin: Methylphenidate may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy

H2-Antagonists: May increase the absorption of Methylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy

Inhalational Anesthetics: Methylphenidate may enhance the hypertensive effect of Inhalational Anesthetics. Risk X: Avoid combination

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination

MAO Inhibitors: May enhance the hypertensive effect of Methylphenidate. Risk X: Avoid combination

PHENobarbital: Methylphenidate may increase the serum concentration of PHENobarbital. Risk C: Monitor therapy

Phenytoin: Methylphenidate may increase the serum concentration of Phenytoin. Risk C: Monitor therapy

Primidone: Methylphenidate may increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations could become elevated. Methylphenidate may increase the serum concentration of Primidone. Risk C: Monitor therapy

Proton Pump Inhibitors: May increase the absorption of Methylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tricyclic Antidepressants: Methylphenidate may enhance the adverse/toxic effect of Tricyclic Antidepressants. Methylphenidate may increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Methylphenidate may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Food Interactions

Food may increase oral absorption

Concerta®: A high fat meal does not alter pharmacokinetics or pharmacodynamics; no evidence of dose dumping occurs when administered with or without food

Metadate CD®: Food delays the early peak by ∼1 hour; a high fat meal increases peak concentrations by 30% and AUC by 17%; one adult study showed no difference in bioavailability when Metadate CD® capsules were opened and contents sprinkled onto 1 tablespoon of applesauce (compared to fasting conditions; Pentikin, 2002).

Methylin®:

Chewable tablets: A high fat meal delays peak concentrations by ∼1 hour, but increases AUC by ∼20% (Note: Magnitude of food effect is similar to immediate release tablets).

Oral solution: A high fat meal delays peak concentrations by ∼1 hour, but increases peak by ∼13% and AUC by ∼25% (Note: Increase in peak concentration and AUC are similar to immediate release tablets).

Ritalin LA®: Compared to fasting, food does not affect the first peak concentration, extent of absorption, or time to second peak concentration; however, the second peak was 25% lower. A high fat meal delays absorption. Compared to fasting, no differences in pharmacokinetics occurred when Ritalin LA® capsules were administered with applesauce. No evidence of dose dumping occurs when administered with or without food.

Pregnancy Risk Factor

C (show table)

Pregnancy Implications

Animal studies have shown teratogenic effects to the fetus. There are no adequate and well-controlled studies in pregnant women. Do not use in women of childbearing age unless the potential benefit outweighs the possible risk.

Monitoring Parameters

Evaluate patients for cardiac disease prior to initiation of therapy with thorough medical history, family history, and physical exam; consider ECG; perform ECG and echocardiogram if findings suggest cardiac disease; promptly conduct cardiac evaluation in patients who develop chest pain, unexplained syncope, or any other symptom of cardiac disease during treatment. Monitor CBC with differential, platelet count, liver enzymes, blood pressure, heart rate, height, weight, appetite, abnormal movements, growth in children. Patients should be re-evaluated at appropriate intervals to assess continued need of the medication. Observe for signs/symptoms of aggression or hostility, or depression. Transdermal system: Also monitor the application site for local adverse reactions and allergic contact sensitization.

Stability

Dispense oral formulations in tight, light-resistant container; Note: Metadate CD® should be dispensed in the original dose pack of 30 capsules

Capsule: Extended release: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Solution: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F).

Tablet:

Chewable: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from moisture.

Extended and sustained release:

Metadate® ER: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

Methylin ER: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light and moisture.

Ritalin SR: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light and moisture.

Immediate release:

Methylin®: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light.

Ritalin®: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Osmotic controlled release (Concerta®): Store at controlled room temperature of 25°C; excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from humidity.

Transdermal system: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Keep patches stored in protective pouch. Once sealed tray or outer pouch is opened, use patches within 2 months; once an individual patch has been removed from the pouch and the protective liner removed, use immediately. Do not refrigerate or freeze.

Mechanism of Action

Produces stimulant effect by activating the brain stem arousal system and cerebral cortex; blocks the reuptake of norepinephrine and dopamine into presynaptic neurons, thus increasing the concentrations of these neurotransmitters in the extraneuronal space.

Pharmacodynamics

Cerebral stimulation:

Maximum effect:

Immediate release tablet: Within 2 hours

Sustained release tablet: Within 4-7 hours

Duration (AAP, 2001):

Immediate release tablet (short-acting): Methylin®, Ritalin®: 3-5 hours

Sustained release, extended release (intermediate-acting): Metadate® ER, Methylin® ER, Ritalin-SR®: 3-8 hours

Extended release (long-acting): Concerta®, Metadate CD®, Ritalin LA®: 8-12 hours

Pharmacokinetics (Adult data unless noted)

Note: Values reported below based on pediatric patient data or combined pediatric and adult data.

Absorption: Oral:

Immediate release products: Readily absorbed

Transdermal: Rate and extent of absorption is increased when applied to inflamed skin or exposed to heat; transdermal absorption may increase with chronic therapy

Distribution: Vd: d-methylphenidate: 2.65 ± 1.11 L/kg; l-methylphenidate: 1.80 ± 0.91 L/kg

Protein binding: 15%

Metabolism: In the liver via hydroxylation (de-esterification by carboxylesterase CES1A1) to ritalinic acid (alpha-phenyl-2-piperidine acetic acid), which has little or no pharmacologic activity

Bioavailability: Chewable tablets and oral solution are bioequivalent to immediate release tablets. Note: A much lower first pass effect occurs with transdermal (vs oral) administration; thus, much lower doses (on a mg/kg basis) given via the transdermal route may still produce higher AUCs, compared to the oral route.

Half-life: 2-4 hours

Time to peak serum concentration:

Chewable tablets, oral solution: 1-2 hours

Extended release tablet (Concerta®): 6-10 hours

Transdermal patch (Daytrana™): Children 6-17 years: 8-10 hours

Elimination: 90% of dose is eliminated in the urine as metabolites and unchanged drug; main urinary metabolite (ritalinic acid) accounts for 80% of the dose; drug is also excreted in feces via bile

Patient Information

(For additional information see "Methylphenidate: Patient drug information")

Read the patient Medication Guide that you receive with each prescription and refill of methylphenidate. Serious cardiac effects or psychiatric adverse effects may occur; notify your physician of any heart problems, high blood pressure, or psychiatric conditions before starting therapy. May reduce the growth rate in children and has been associated with worsening of aggressive behavior; notify your physician if your child displays aggression or hostility; make sure your physician monitors your child’s weight and height. Avoid caffeine and the herbal medicine St John's wort. May be habit-forming; avoid abrupt discontinuation after prolonged use. May cause dizziness or drowsiness and impair ability to perform activities requiring mental alertness or physical coordination. Notify physician if blurred vision occurs. Intact Concerta® tablet shell may appear in stool (this is normal). Report the use of other medications and herbal or natural products to your physician and pharmacist. Seek immediate medical attention if chest pain, vomiting, or difficulty in breathing or swallowing occur after taking chewable tablet. When using transdermal patches, avoid exposing application site to external heat sources (eg, hair dryers, electric blankets, heating pads, heated water bed); patches may be irritating to the skin; inform physician if skin rash or irritation occurs; do not use patch if swelling or blistering occurs

Additional Information

Methylphenidate is a racemic mixture of d- and l-enantiomers; the d-enantiomer is more active than the l-enantiomer. Treatment with methylphenidate should include “drug holidays” or periodic discontinuation in order to assess the patient's requirements, decrease tolerance and limit suppression of linear growth and weight. Medications used to treat ADHD should be part of a total treatment program that may include other components such as psychological, educational, and social measures. Concerta®, Metadate CD®, and Ritalin LA® are formulated to deliver methylphenidate in a biphasic release profile; Concerta® is an osmotic controlled release formulation, with an immediate release (within 1 hour) outer coating; once daily Concerta® has been shown to be as effective as immediate release methylphenidate tablets administered 3 times/day (Pelham, 2001). Metadate CD® capsules contain both immediate release beads (30% of the dose) and extended release beads (70% of the dose). Ritalin LA® capsules contain both immediate release beads (50% of the dose) and enteric coated, delayed release beads (50% of the dose). Methylin®, Methylin® ER, and Ritalin-SR® tablets are color and additive free; Methylin® oral solution is colorless. Concerta® tablets may be seen on abdominal x-ray under certain conditions (eg, when digital enhancing techniques are used).

Daytrana™ Transdermal System consists of an adhesive-based matrix containing active drug which is dispersed in acrylic adhesive that is dispersed in a silicone adhesive. The patch consists of 3 layers: A polyester/ethylene vinyl acetate laminate (outside) film backing, the adhesive layer containing methylphenidate, and a flouropolymer-coated polyester protective liner (which must be removed before application). Long-term use of the transdermal system or Concerta ® >7 weeks, Metadate® CD >3 weeks, and Ritalin ® LA >2 weeks have not been adequately studied; long-term usefulness should be periodically re-evaluated for the individual patient