Class: Respiratory and CNS Stimulants
VA Class: CN802
Chemical Name: d,l (racemic) methyl a-phenyl-2-piperidineacetate hydrochloride
Molecular Formula: C₁₄H₁₉NO₂•ClH
CAS Number: 298-59-9
Brands: Aptensio, Concerta, Daytrana, Metadate, Methylin, Quillivant, Ritalin

Medically reviewed by Drugs.com. Last updated on Nov 13, 2020.

• Overview
• Side Effects
• Dosage
• FAQ
• Professional
• Tips
• Interactions
• More

Introduction

Piperidine-derivative stimulant; ¹¹⁸ pharmacologic actions qualitatively similar to those of amphetamines.^a

Uses for Methylphenidate

Attention Deficit Hyperactivity Disorder (ADHD)

Treatment of ADHD, alone or combined with behavioral treatment, as an adjunct to psychological, educational, social, and other remedial measures in carefully selected children ≥6 years of age, adolescents, and adults.^{100 101 102 103 104 107 114 115 116 117 118 125 145 147 149 151 152 157 158 168}

A drug of choice for the management of ADHD.^{101 103 104 105 106 107 110 115 116 122 127}

Used effectively in the management of ADHD in adolescents and adults, but experience is far less extensive than in children, and potential age-related differences in response remain to be elucidated.^{101 102 103 104 105 106 107 110}

Narcolepsy

Symptomatic treatment of narcolepsy.^{114 145}

Methylphenidate Dosage and Administration

General

• Carefully adjust dosage according to individual requirements and response.^{118 125 129}

• For patients whose symptoms are not severe outside school, may attempt drug holidays for all or part of the summer to assess continuing efficacy and need for therapy, as well as to minimize adverse effects.¹⁰⁴

• Discontinue therapy if a beneficial effect is not attained after appropriate dosage adjustment over 1 month.¹¹⁴

• If paradoxical aggravation of symptoms occurs, reduce dosage or discontinue the drug.¹¹⁴

• Periodically discontinue therapy to assess the patient’s condition.¹¹⁴

Administration

Administer orally^{114 118 125 129 145 157 158 168} or percutaneously by topical application of a transdermal system.¹⁴⁷

Oral Administration

Conventional Tablets, Chewable Tablets, or Oral Solution

Administer orally 2 or 3 times daily.^{114 145 151 152}

The manufacturers recommend that conventional tablets, chewable tablets, or oral solution be taken 30–45 minutes before meals.^{114 145 151 152}

To avoid insomnia, administer the last daily dose before 6 p.m.^{114 145 151 152}

Administer chewable tablets with a full glass (i.e., ≥240 mL [8 ounces]) of water or other fluid to avoid choking.¹⁵² (See GI Effects under Cautions and also see Advice to Patients.)

Extended-release Tablets (Metadate ER, Ritalin–SR; generics)

Swallow tablets whole; do not crush or chew.^{114 151 158}

May be used once the daily dosage has been titrated using conventional tablets (when the 8-hour dosage of the extended-release preparation corresponds to the titrated 8-hour dosage of the conventional tablets).^{114 151 158}

Extended-release Capsules (Aptensio XR, Metadate CD, Ritalin LA; generics)

Administer orally once daily in the morning.^{125 129 168}

Manufacturer states that Metadate CD extended-release capsules should be administered before breakfast.¹²⁵ Manufacturer states that administration of Ritalin LA relative to timing and composition of meals may need to be individually adjusted.¹²⁰ Manufacturer states that Aptensio XR may be administered without regard to meals, but should be administered in a consistent manner relative to food intake.¹⁶⁸

Swallow capsules whole; do not crush, chew, or divide.^{125 129 168}

Alternatively, open capsule and sprinkle contents (pellets) on a small amount of applesauce; swallow immediately without chewing.^{125 129 168}

Patients receiving extended-release capsules should avoid consuming alcohol; alcohol may result in more rapid release of drug from these formulations.^{125 149 168}

Manufacturers state that extended-release capsules may be used to initiate methylphenidate therapy^{125 129} or for continued therapy in patients being switched from other methylphenidate formulations (see Switching to Extended-release Capsules [Metadate CD, Ritalin LA; generics] under Dosage and Administration).¹²⁹

Extended-release Trilayer Core Tablets (Concerta; generics)

Administer orally once daily in the morning without regard to meals.¹¹⁸

Swallow tablets whole; do not crush or chew.¹¹⁸

May be used to initiate methylphenidate therapy or for continued therapy in patients being switched from other methylphenidate formulations (see Switching to Extended-release Trilayer Core Tablets [Concerta; generics] under Dosage and Administration).¹¹⁸

Powder for Extended-release Suspension (Quillivant XR)

Administer orally once daily in the morning without regard to meals.¹⁵⁷

Must be reconstituted prior to dispensing.¹⁵⁷

To reconstitute powder, tap bottle until the powder flows freely, then remove bottle cap and add appropriate amount of water (53, 105, 131, or 158 mL of water to a bottle containing 300, 600, 750, or 900 mg, respectively, of the drug) to yield an extended-release suspension containing 25 mg/5 mL.¹⁵⁷ Insert adapter into neck of bottle and replace bottle cap.¹⁵⁷ Shake vigorously with back and forth motion for ≥10 seconds.¹⁵⁷

Use the bottle adapter and oral dosing dispenser supplied by manufacturer to administer the oral suspension.¹⁵⁷ Adapter should remain in place as long as the bottle is in use (up to 4 months).¹⁵⁷

To dispense a dose, insert the oral dosing dispenser into the adapter in the upright bottle, then invert the bottle and withdraw the appropriate dose into the oral dosing dispenser.¹⁵⁷ Consult manufacturer's patient information for more detailed information on administration.¹⁵⁷

Transdermal Administration

Apply once daily in the morning, 2 hours before an effect is needed; remove 9 hours after application.¹⁴⁷

Apply system immediately after opening individually sealed package and removing protective liner.¹⁴⁷

Do not use if package seal is broken.¹⁴⁷ Do not cut transdermal systems.¹⁴⁷ After separating the system from the protective liner, inspect the liner to ensure that no adhesive (which contains the drug) has been transferred to the liner.¹⁴⁷ Discard the transdermal system if adhesive transfer has occurred or if the system is torn, appears to be damaged, or is difficult to separate from the liner.¹⁴⁷ Use only intact transdermal systems.¹⁴⁷

Apply the transdermal system to a clean, dry area of the hip that is not oily, damaged, or irritated; avoid applying to the waistline or to areas under tight clothing, since system may rub off.¹⁴⁷ Press system firmly in place with palm of hand for approximately 30 seconds, ensuring good contact with the skin, particularly around the edges.¹⁴⁷ Alternate application sites daily (e.g., opposite hip) if possible.¹⁴⁷

Do not apply topical preparations (e.g., corticosteroids) immediately prior to system application; effects on adhesion, methylphenidate absorption, or adverse corticosteroid effects are not known.¹⁴⁷

Exposure to water during bathing, swimming, or showering can affect adherence to the skin.¹⁴⁷ Do not apply or reapply transdermal systems with dressings, tape, or other common adhesives.¹⁴⁷ If a system does not fully adhere to the skin upon application or becomes partially or fully dislodged during the intended period of use, replace it with a new system applied at a different site; do not exceed total wear time of 9 hours per day regardless of number of systems used.¹⁴⁷

Remove system by slowly peeling it off the skin.¹⁴⁷ If necessary to facilitate removal, gently apply an oil-based product (i.e., petroleum jelly, olive oil, mineral oil) to the edges of the system and gently work the oil underneath the edges.¹⁴⁷ To remove any adhesive remaining on the skin after system removal, apply an oil-based product to the application site to gently loosen and remove residual adhesive.¹⁴⁷ In the unlikely event that a system remains tightly adhered to the skin despite these measures, patient's clinician or pharmacist should be consulted.¹⁴⁷ Do not use nonmedical adhesive removers and acetone-based products (i.e., nail polish remover) to remove the system or adhesive.¹⁴⁷

After removal, fold system so that the adhesive side adheres to itself, then flush down the toilet or dispose of in an appropriate lidded container.¹⁴⁷ For unused systems, remove from packaging, separate from the protective liner, fold so that the adhesive side adheres to itself, and then flush down the toilet or dispose of in an appropriate lidded container.¹⁴⁷

Encourage parents or caregiver to record and monitor the application and removal times and method of disposal for each system.¹⁴⁷

Dosage

Available as methylphenidate and methylphenidate hydrochloride; dosage of methylphenidate hydrochloride is expressed in terms of the salt.^{114 118 125 129 145 147 152}

Pediatric Patients

ADHD

Initial Therapy with Conventional Tablets, Chewable Tablets, or Oral Solution

Oral

Initially, 5 mg twice daily, before breakfast and lunch.^{114 145 152} Increase dosage by 5–10 mg daily at weekly intervals based on response and tolerance, up to 60 mg daily; administer daily dosage in 2 or 3 divided doses.^{114 145 152}

Some clinicians recommend an initial dosage of 0.25 mg/kg daily; if adverse effects are not observed, double daily dosage each week until 2 mg/kg daily is reached.^a

Alternatively, dosage has been titrated over 28 days via daily-switch titration involving 5 randomly ordered repeats each of placebo and 5-, 10-, 15-, or 20-mg daily dosages (higher for children weighing >25 kg); each dose is repeated at breakfast and lunch, with a half dose given in the afternoon.¹¹⁵ The best dosage is selected based on clinical assessment of response.¹¹⁵

Switching to Extended-release Tablets (Metadate ER, Ritalin-SR; generics)

Oral

Extended-release tablets can be substituted for conventional tablets at the nearest equivalent total daily dosage (e.g., patients receiving 10 mg as conventional tablets twice daily can be switched to 20 mg as extended-release tablets once daily).^{114 151 158}

Usual dosage: 20–60 mg daily, given as 20–40 mg once daily or as 40 mg in the morning and 20 mg in the early afternoon.¹²⁷

Initial Therapy with Extended-release Capsules (Aptensio XR, Metadate CD, Ritalin LA; generics)

Oral

Aptensio XR: Initially, 10 mg once daily in the morning.¹⁶⁸ Increase dosage by 10 mg daily at weekly intervals, up to 60 mg daily.¹⁶⁸

Metadate CD: Initially, 20 mg once daily in the morning.^{125 126 127} Increase dosage by 10 or 20 mg daily at weekly intervals, up to 60 mg daily.¹²⁵

Ritalin LA: Initially, 20 mg once daily in the morning.^{127 129} Alternatively, initiate with 10 mg once daily when a lower initial dosage is appropriate.¹²⁹ Increase dosage by 10 mg daily at weekly intervals, up to 60 mg daily.¹²⁹

Switching to Extended-release Capsules (Metadate CD, Ritalin LA; generics)

Oral

Adjust dosage of Metadate CD by 10 or 20 mg daily at weekly intervals, up to 60 mg daily.¹²⁵

Adjust dosage of Ritalin LA by 10 mg daily at weekly intervals, up to 60 mg daily.¹²⁹

For other conventional tablet regimens, substitute Ritalin LA at the nearest daily dosage based on clinical judgment.¹²⁹

Initial Therapy with Extended-release Oral Suspension (Quillivant XR)

Oral

Initially, 20 mg once daily in the morning.¹⁵⁷ Increase dosage by 10–20 mg daily at weekly intervals, up to 60 mg daily.¹⁵⁷

Initial Therapy with Extended-release Trilayer Core Tablets (Concerta; generics)

Oral

Initially, 18 mg once daily in the morning.¹¹⁸ If adequate response does not occur, increase dosage at approximately weekly intervals in increments of 18 mg daily up to 54 mg daily in children 6–12 years of age or 72 mg daily (maximum 2 mg/kg daily) in adolescents 13–17 years of age.¹⁶² Some clinicians state that dosage in children 6–12 years of age may be increased to 72 mg daily.¹²⁷

Switching to Extended-release Trilayer Core Tablets (Concerta; generics)

Oral

For patients being switched from other drugs to methylphenidate (as extended-release trilayer core tablets), follow dosage recommendations for initial therapy with the extended-release trilayer core tablets.¹⁶²

Initial dosage as extended-release trilayer core tablets in patients being switched from conventional tablets should not exceed 72 mg daily.¹⁶² Adjust dosage at weekly intervals in increments of 18 mg daily, up to 72 mg once daily.¹⁶²

A 27-mg extended-release trilayer core tablet also is available for patients who require a dosage in between 18 mg daily and 36 mg daily.¹⁶²

Initial Therapy with or Switching to Transdermal System

Transdermal

Individualize dosage titration, final dosage, and wear time according to patient’s needs and response.¹⁴⁷

Initially, apply one system delivering 10 mg/9 hours once daily (for initial therapy or for patients switching from other methylphenidate preparations).¹⁴⁷ Increase dosage at weekly intervals, based on response and tolerance, by using the next larger dosage system (i.e., 1 system delivering 15 mg/9 hours, then 1 system delivering 20 mg/9 hours, and then 1 system delivering 30 mg/9 hours).¹⁴⁷

If shorter duration of effect is desired or if late-day adverse effects appear, may remove system earlier than 9 hours.¹⁴⁷ If aggravation of symptoms or other adverse events occur, reduce dosage or wear time or, if necessary, discontinue therapy.¹⁴⁷

Adults

ADHD

Initial Therapy with Extended-release Trilayer Core Tablets (Concerta; generics)

Oral

Initially, 18 or 36 mg once daily in the morning.¹⁶² If adequate response does not occur, increase dosage at approximately weekly intervals in increments of 18 mg daily, up to 72 mg daily.¹⁶²

Narcolepsy

Oral

Usual dosage of 10 mg (as conventional tablets or oral solution) 2 or 3 times daily; dosage range of 10–60 mg daily.^{114 145}

Prescribing Limits

Pediatric Patients

ADHD

Conventional Tablets, Chewable Tablets, Oral Solution, Extended-release Tablets, Extended-release Capsules, and Extended-release Oral Suspension

Oral

Maximum 60 mg daily.^{114 125 129 145 149 151 152 157 158 168}

Extended-release Trilayer Core Tablets (Concerta; generics)

Oral

Maximum dosage of 54 mg daily for children 6–12 years of age or 72 mg daily (maximum 2 mg/kg daily) for adolescents 13–17 years of age;¹⁶² however, some clinicians state that dosage for children 6–12 years of age may be increased to 72 mg daily.¹²⁷

Adults

ADHD

Extended-release Trilayer Core Tablets (Concerta; generics)

Oral

Maximum 72 mg daily.¹⁶²

Narcolepsy

Oral

Maximum 60 mg daily.¹¹⁴

Cautions for Methylphenidate

Contraindications

• Marked anxiety, tension, and agitation.^{114 118 125 129 145 147 151 152 158}

• Glaucoma.^{114 118 125 129 145 147 151 152 158}

• Motor tics or a family history or diagnosis of Tourette’s syndrome.^{114 118 125 129 145 147 151 152 158} However, the AAP states that the presence of tics before or during medical management of ADHD is not an absolute contraindication to stimulant drug use.¹²⁷

• Concomitant or recent (within 14 days) administration of MAO inhibitors.^{114 118 129 145 147 151 152 158 168} (See Specific Drugs under Interactions.)

• Known hypersensitivity to methylphenidate or any ingredient in the formulation.^{114 118 129 145 147 151 152 158}

Warnings/Precautions

Warnings

Abuse Potential

Marked tolerance and psychologic dependence with varying degrees of abnormal behavior may occur with chronic abuse.^{114 125 145 147 149 151 152 158 162} (See Boxed Warning.)

Psychotic episodes can occur, particularly with parenteral abuse.^{114 125 145 147 149 151 152 158 162} Abuse by unintended routes of administration (e.g., chewing, snorting, or injecting formulation) can result in overdosage and death.^{157 168}

Manifestations of stimulant abuse include increased heart rate, respiratory rate, BP, and/or sweating; dilated pupils; hyperactivity, restlessness, insomnia, loss of coordination, and tremors; flushed skin; decreased appetite; and vomiting and/or abdominal pain.^{157 168} Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation also observed.^{157 168}

Use with caution in patients with a history of drug or alcohol dependence.^{114 118 147 148 149 150 152 a} Caution may be indicated in patients with comorbid conduct disorder or a chaotic family.¹⁰⁴ If the risk of drug abuse by the patient or the patient’s peers or family is considered high, a nonstimulant drug may be preferable.¹⁰⁴

Monitor patients for signs of abuse and dependence; periodically reevaluate the need for continued therapy.^{157 168}

Withdrawal Effects

Abrupt withdrawal following prolonged high-dose administration may result in withdrawal symptoms, including extreme fatigue and depression.^{157 168} Severe depression may occur during withdrawal from abusive use; careful supervision required.^{114 125 145 147 149 151 152 158 162}

Withdrawal following prolonged therapeutic administration may unmask symptoms of the underlying disorder, which may require follow-up.^{114 125 145 147 149 151 152 158 162}

Sudden Death and Serious Cardiovascular Events

Sudden unexplained death, stroke, and MI reported in adults with ADHD receiving usual dosages of stimulants; sudden death also reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of the drugs.^{114 118 125 129 145 147 148 149 150 152 168}

Although an initial epidemiologic study showed an association between use of stimulants (e.g., methylphenidate) and sudden unexplained death in healthy children and adolescents,^{153 154 155} several subsequent large epidemiologic studies in children and young adults or in adults 25–64 years of age found no association between ADHD drug use (stimulants, atomoxetine, pemoline [no longer commercially available in US]) and serious cardiovascular events (MI, stroke, sudden cardiac death), although small increases in cardiovascular risk could not be excluded.^{164 165 166 167}

Thoroughly review medical history (including evaluation for family history of sudden death or ventricular arrhythmia) and perform physical examination in all children, adolescents, and adults being considered for stimulant therapy; if initial findings suggest presence of cardiac disease, perform further cardiac evaluation (e.g., ECG, echocardiogram).^{114 118 147 148 149 150 168}

In general, avoid use of CNS stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, CAD, or other serious cardiac conditions.^{114 118 147 148 149 150 152 164 165 168}

Patients who develop exertional chest pain, unexplained syncope, or other manifestations suggestive of cardiac disease during stimulant therapy should undergo prompt cardiac evaluation.^{114 118 147 148 149 150 168}

Effects on BP and Heart Rate

Possible modest increases in average BP (i.e., by about 2–4 mm Hg) and heart rate (i.e., by about 3–6 bpm); larger increases may occur.^{114 147 148 149 150 168} Modest increases not expected to have short-term sequelae; however, monitor all patients for larger changes in BP and heart rate.^{114 118 147 148 149 150 164 165 168}

Caution advised in patients with underlying medical conditions that might be affected by increases in BP or heart rate (e.g., hypertension, heart failure, recent MI, ventricular arrhythmia).^{114 118 147 148 149 150 164 165}

Exacerbation or Precipitation of Psychotic Symptoms

May exacerbate symptoms of behavior disturbance and thought disorder in patients with preexisting psychotic disorder.^{114 118 147 148 149 150 152 157 168}

Psychotic symptoms (e.g., hallucinations, delusional thinking) may occur with usual dosages in children and adolescents without prior history of psychotic illness.^{114 118 147 148 149 150 168} If psychotic symptoms occur, consider causal relationship to stimulants, and discontinue therapy as appropriate.^{114 118 147 148 149 150}

Precipitation of Manic Symptoms

May precipitate mixed or manic episodes in ADHD patients with comorbid bipolar disorder; use with caution in these patients.^{114 118 147 148 149 150 157 168} Prior to initiating therapy, carefully screen patients with ADHD and comorbid depressive symptoms to identify risk for bipolar disorder; screening should include a detailed psychiatric history (e.g., family history of suicide, bipolar disorder, or depression).^{114 118 147 148 149 150 168}

Manic symptoms may occur with usual dosages in children and adolescents without prior history of mania.^{114 118 147 148 149 150} If manic symptoms occur, consider causal relationship to stimulants, and discontinue therapy as appropriate.^{114 118 147 148 149 150}

Aggression

Aggressive behavior and hostility (frequently observed in children and adolescents with ADHD) reported in patients receiving drug therapy for ADHD.^{114 118 147 148 149 150} No systematic evidence that stimulants cause these adverse effects; however, monitor patients beginning treatment for ADHD for onset or worsening of aggressive behavior or hostility.^{114 118 147 148 149 150 157 158}

Priapism

Prolonged and painful erections, sometimes requiring surgical intervention, reported in adult and pediatric patients.^{114 125 145 147 149 151 152 157 158 159 162 168} Priapism often reported following an increase in dosage; also has occurred during temporary interruptions in therapy (e.g., drug holidays) or following drug discontinuance.^{114 125 145 147 149 151 152 157 158 159 162 168} Risk of permanent penile damage if not treated immediately.¹⁵⁹

Use caution if considering change in therapy because of this risk; certain alternative ADHD treatments (e.g., atomoxetine) also may cause priapism.¹⁵⁹

Peripheral Vascular Effects

Peripheral vascular disorders, including Raynaud’s phenomenon, reported in patients in all age groups receiving stimulants at therapeutic dosages and at various times throughout treatment course.^{114 125 145 147 149 151 152 157 158 162 168} Manifestations usually intermittent and mild, but ulceration of digits and/or breakdown of soft tissue occur rarely.^{114 125 145 147 149 151 152 157 158 162 168} Carefully observe for digital changes.^{114 125 145 147 149 151 152 157 158 162 168}

Improvement generally occurs following dosage reduction or drug discontinuance; however, some patients may require further evaluation (e.g., referral to rheumatologist).^{114 125 145 147 149 151 152 157 158 162 168}

Growth Suppression

Long-term (i.e., >14 months) administration expected to cause at least a temporary suppression of normal weight and/or height patterns in some children and adolescents.^{114 118 127 147 148 149 150 152}

Manufacturers recommend monitoring growth during treatment; patients not growing or gaining weight as expected may require temporary discontinuance of treatment.^{114 118 147 148 149 150} However, AAP states that studies of stimulants in children found little or no decrease in expected height, with any decrease in growth early in treatment being compensated for later on.¹²⁷

Seizures

Possible lowering of seizure threshold in patients with history of seizures, in those with prior EEG abnormalities but no history of seizures, and, very rarely, in those without history of seizures and with no prior evidence of EEG abnormalities.^{114 118 147 148 149 150 152 a} If seizures occur, discontinue therapy.^{114 118 147 148 149 150 152 a}

GI Disorders

Extended-release trilayer core tablets generally should not be used in patients with severe preexisting GI narrowing; obstruction may occur.¹¹⁸

Adverse Ocular Effects

Visual disturbances (e.g., difficulty with accommodation, blurred vision) and eye pain reported with stimulants.^{114 125 129 145 147 148 149 150 152 147 157 162 168}

Hereditary Disorders of Carbohydrate Metabolism

Metadate CD extended-release capsules contain sucrose and should not be used in those with hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency.¹²⁵

Metadate ER extended-release tablets contain lactose and should not be used in those with hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.¹⁵⁸

Chemical Leukoderma

Permanent depigmentation or hypopigmentation reported in patients receiving methylphenidate transdermal system.¹⁶³ Usually limited to application sites,¹⁶³ but skin color changes affecting other areas of the body also reported.¹⁶³ Time to onset has ranged from 2 months to 4 years; affected areas up to 8 inches in diameter reported.¹⁶³

Monitor skin for loss of pigmentation, especially at application sites.¹⁶³ If such changes occur, discontinue transdermal methylphenidate and consider alternative therapy.¹⁶³

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including angioedema and anaphylaxis, reported.^{114 125 129 145 147 152 157 158 162 168}

Contact Sensitization

Possible contact sensitization following use of transdermal system.¹⁴⁷ Discontinue transdermal therapy if contact sensitization is suspected (erythema accompanied by evidence of a more intense local reaction [e.g., edema, papules, vesicles] that does not substantially improve within 48 hours or that spreads beyond the application site).¹⁴⁷

Development of localized contact sensitization to methylphenidate during transdermal therapy may be associated with development of systemic sensitization with subsequent oral administration.¹⁴⁷ Manifestations of systemic sensitization may include a flare-up of previous dermatitis or of prior positive patch test sites, or generalized skin eruptions in previously unaffected skin.¹⁴⁷ Other systemic reactions may include headache, fever, malaise, arthralgia, diarrhea, or vomiting.¹⁴⁷

If contact sensitization occurs with transdermal therapy, monitor patients closely if oral therapy with the drug is initiated.¹⁴⁷ Some patients sensitized to methylphenidate by exposure to transdermal system may not be able to receive methylphenidate in any form.¹⁴⁷

General Precautions

Nervous System Effects

Possible motor tics.¹¹⁸ (See Contraindications under Cautions.)

Hematologic Effects

Thrombocytopenia and/or easy bruisability, epistaxis, and gingival bleeding; leukopenia; anemia; pancytopenia; or eosinophilia reported rarely.^{114 157 162 168 a}

Manufacturers recommend periodic monitoring of CBC (with differential) and platelet counts during prolonged therapy;^{114 118} however, AAP and many clinicians consider routine hematologic monitoring unnecessary in the absence of clinical signs (e.g., fever, sore throat, unusual bleeding or bruising) suggestive of hematologic toxicity.^{a 127}

Radiographic Examinations

Extended-release trilayer core tablet may be visible on abdominal radiographs under certain circumstances, particularly when digital enhancing techniques are utilized.¹¹⁸

GI Effects

Administration of chewable tablets without adequate fluid may cause tablet contents to swell, resulting in blockage of throat or esophagus and, possibly, choking.¹⁵² Therefore, administer with a full glass (i.e., ≥240 mL [8 ounces]) of water or other fluid.¹⁵² Do not administer in patients with difficulty swallowing.¹⁵² (See Advice to Patients.)

Phenylketonuria

Methylin 2.5-, 5-, and 10-mg chewable tablets contain aspartame (NutraSweet), which is metabolized in the GI tract to provide 0.42, 0.84, and 1.68 mg, respectively, of phenylalanine per tablet.¹⁵²

Exposure of Transdermal Application Site to External Heat

Percutaneous absorption of methylphenidate from the transdermal system may be increased, potentially resulting in overdosage, if the application site is exposed to direct external heat sources (e.g., hair dryers, heating pads, electric blankets, heated water beds) while the transdermal system is being worn.¹⁴⁷

Specific Populations

Pregnancy

Category C.^{114 118 125 129 147 151 158}

Lactation

Limited data (case reports) suggest breast-fed infants receive 0.2–0.7% of the maternal weight-adjusted dosage of methylphenidate; milk-to-plasma ratios of 1.1–2.7 reported.¹⁶⁸ Adverse effects on breast-fed infants or on milk production not reported to date; however, any long-term neurodevelopmental effects are unknown.¹⁶⁸

Consider developmental and health benefits of breast-feeding, the importance of methylphenidate to the woman, and any potential adverse effects of either the drug or the underlying maternal condition on the breast-fed infant.¹⁶⁸

If used in a nursing woman, monitor breast-fed infant for adverse effects (e.g., agitation, anorexia, reduced weight gain).¹⁶⁸

Pediatric Use

Safety and efficacy not established in children <6 years of age.^{114 118 125 129 145 147 151 152 158}

Aggressive behavior, hostility, and psychotic (e.g., hallucinations, delusional thinking) or manic symptoms reported in children and adolescents receiving stimulants for management of ADHD.^{114 118 147 148 149 150} (See Warnings under Cautions.)

Sudden death reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of stimulants.^{114 118 147 148 149 150 152} (See Sudden Death and Serious Cardiovascular Events under Cautions.)

Long-term administration expected to cause at least a temporary suppression of normal weight and/or height patterns in some children and adolescents.^{114 118 127 147 148 149 150 152} (See Growth Suppression under Cautions.)

Common Adverse Effects

Nervous system (insomnia, delayed sleep onset, headache, nervousness, jitteriness, social withdrawal, anxiety, restlessness, affect lability, agitation, irritability, dizziness, vertigo, tremor), cardiovascular (increased BP, increased heart rate, tachycardia, palpitations), GI (decreased appetite/anorexia, nausea, abdominal pain, dyspepsia, dry mouth, vomiting), and other (weight loss, blurred vision, hyperhidrosis, pyrexia, tics) effects.^{114 118 125 126 127 129 147 157 158 168}

Interactions for Methylphenidate

Not metabolized by CYP isoenzymes; does not inhibit CYP isoenzymes.^{125 149}

Specific Drugs

Methylphenidate Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration.^{118 125 126 127 129 130 152} Low oral bioavailability (10–52%) suggests substantial first-pass metabolism.^{129 147}

Oral solution and chewable tablets are bioequivalent to conventional tablets.^{145 152}

Extended-release tablets are absorbed more slowly but to the same extent as conventional tablets.^{a 151 158}

Relative bioavailability of Ritalin LA extended-release capsules given once daily is similar to that of conventional tablets administered at the same total daily dosage in 2 divided doses given 4 hours apart.¹²⁹

Peak plasma concentrations and AUC were slightly lower for Metadate CD extended-release capsules (20 mg once daily) than for conventional tablets (10 mg twice daily).^{125 126}

Relative bioavailability of Aptensio XR extended-release capsules given once daily is comparable to that of conventional tablets administered 3 times daily.¹⁶⁸

Relative bioavailability of the extended-release oral suspension (single 60-mg dose) is 95% that of immediate-release oral solution (given as two 30-mg doses 6 hours apart).¹⁵⁷

Relative bioavailability of extended-release trilayer core tablets administered at a dosage of 18 mg once daily is similar to that of conventional tablets administered at a dosage of 5 mg 3 times daily (given every 4 hours).¹¹⁸

Alcohol increases the rate of drug release in vitro from the extended-release capsules but not from extended-release trilayer core tablets (Concerta); 98 or 84% of the drug was released from Ritalin LA 40-mg or Metadate CD 60-mg capsules within the first hour at an alcohol concentration of 40%,^{125 149} and 96% was released from Aptensio XR 80-mg capsules within 2 hours at an alcohol concentration up to 40%.¹⁶⁸ Results are considered representative for available strengths of the respective preparations.^{125 149 162 168}

For timing of peak plasma concentrations for oral formulations, see Table 4.

Peak plasma methylphenidate concentrations for transdermal systems are attained in about 10 hours (single-dose application) or 8 hours (repeated applications of systems worn for up to 9 hours).¹⁴⁷ Average lag of 2 hours until d-methylphenidate is detectable in plasma after single-dose application; with repeated administration, low concentrations of the drug are detected earlier because of carryover effect.¹⁴⁷

When applied to inflamed skin, time to peak plasma concentrations decreases (to 4 hours) and peak plasma concentration and AUC increase by threefold compared with application to intact skin.¹⁴⁷ When heat is applied to transdermal system after application, peak plasma concentration occurs 0.5 hour earlier, and median peak plasma concentration and AUC are 2-fold and 2.5-fold higher, respectively, compared to application without heat.¹⁴⁷

Possible increased transdermal absorption following repeated administration.¹⁴⁷ Steady state likely to be achieved by approximately day 14 of dosing.¹⁴⁷

Because of substantially greater first-pass metabolism following oral compared with transdermal administration, a lower transdermal dose of methylphenidate may result in greater systemic exposure to d-methylphenidate than a higher (on a mg/kg basis) oral dose of the drug.¹⁴⁷ Little, if any, l-methylphenidate is systemically available following oral administration; however, systemic exposure to l-methylphenidate following transdermal administration is almost as great as that to d-methylphenidate.¹⁴⁷

Duration

Effects persist for 3–6 hours for conventional tablets, about 3–8 hours for extended-release tablets, and about 8–12 hours for extended-release trilayer core tablets, extended-release capsules, and extended-release oral suspension.^{118 125 126 127 129 130 157 168}

Food

Chewable tablets: Administration with high-fat meal delays time to peak plasma concentration by approximately 1 hour and increases AUC by about 20%; magnitude of food effect is comparable to that observed with conventional tablets.¹⁵²

Oral solution: Administration with high-fat meal delays time to peak plasma concentration by approximately 1 hour and increases peak plasma concentration and AUC by about 13 and 25%, respectively.¹⁴⁵

Extended-release oral suspension: Administration with high-fat meal reduces time to peak concentration by approximately 1 hour and increases peak plasma concentration and AUC by approximately 28 and 19%, respectively; not considered clinically important.¹⁵⁷

Extended-release capsules (Aptensio XR, Ritalin LA, Metadate CD): High-fat meal may alter absorption characteristics; opening the capsules and sprinkling the contents on applesauce does not alter bioavailability.^{125 129 168}

Extended-release trilayer core tablets: High-fat meal does not alter pharmacokinetics.¹¹⁸

Distribution

Extent

Extent of distribution in humans is unknown.^a

Plasma Protein Binding

About 10–33%.¹⁴⁹

Elimination

Metabolism

Metabolized primarily by de-esterification by carboxylesterase 1A1 to form d-ritalinic acid, which has little or no pharmacologic activity.^{118 125 129 145 147 149 152}

Elimination Route

Excreted as metabolites (principally as ritalinic acid), mostly in urine^{a 118 125} and a small amount in feces.¹²⁹

Clearance increases with increasing weight; thus, patients with higher body weight may have lower exposures to total methylphenidate at similar doses.¹¹⁸

Half-life

For methylphenidate elimination half-lives reported for various methylphenidate formulations, see Table 5.

Stability

Storage

Oral

Conventional, Chewable, and Extended-release Tablets

Room temperature, generally 20–25°C; consult manufacturer's labeling for specific recommendation.^{114 151 152 158} Protect from moisture.^{114 151 152 158}

Extended-release Capsules

Room temperature, generally 20–25°C; consult manufacturer's labeling for specific recommendation.^{125 149 168}

Extended-release Trilayer Core Tablets

25°C (may be exposed to 15–30°C).¹¹⁸ Protect from moisture.¹¹⁸

Solution

20–25°C.¹⁴⁵

Powder for Suspension

25°C (may be exposed to 15–30°C).¹⁵⁷

Following reconstitution, 25°C (may be exposed to 15–30°C) in original container for up to 4 months.¹⁵⁷

Topical

Transdermal System

25°C (may be exposed to 15–30°C).¹⁴⁷ Use all the systems in a tray within 2 months of opening the tray.¹⁴⁷ Apply the system to the skin immediately after removal from the individually sealed package.¹⁴⁷ Do not freeze or refrigerate.¹⁴⁷

Actions

• Appears to block norepinephrine and dopamine reuptake into the presynaptic neuron and increases their release into the extraneuronal space.^{118 125 129} Mechanism of action involved in the central effect not determined.^a

• Pharmacologic actions include CNS stimulation (e.g., increased motor activity, mental alertness, diminished sense of fatigue, brighter spirits, mild euphoria), respiratory stimulation, and weak sympathomimetic activity;^a also produces an anorexigenic effect.¹¹⁴

• At usual therapeutic dosages, exhibits only moderate effects on the peripheral circulatory system.^a

• Racemic mixture; the d-enantiomer is the more pharmacologically active enantiomer.^{118 125 129}

• No clinically important changes in corrected QT (QT_c) interval observed in healthy individuals following 40-mg dose of extended-release dexmethylphenidate hydrochloride (the more active enantiomer).^{114 149 151 158}

Advice to Patients

• Provide patient or caregiver with a copy of the manufacturer’s patient information (medication guide);^{118 125 129 147} discuss and answer questions about its contents as needed.^{114 118 125 147 149 151} Instruct patient or caregiver to read and understand contents of medication guide before initiating therapy and each time the prescription is refilled.^{114 118 125 147 149 151}

• Importance of administering the last daily dose of conventional tablets or oral solution before 6 p.m.^{114 145 152}

• In patients receiving chewable tablets, importance of administering with a full glass (i.e., ≥240 mL [8 ounces]) of water or other fluid to avoid choking.¹⁵² Importance of seeking immediate medical attention if chest pain, vomiting, or difficulty in swallowing or breathing occurs following administration.¹⁵²

• Importance of not crushing or chewing extended-release tablets, extended-release capsules, or extended-release trilayer core tablets.^{118 125 129 168} Capsules may be opened and the contents sprinkled on applesauce.^{125 129 168}

• In patients receiving extended-release capsules, importance of not consuming alcohol, since alcohol may result in more rapid release of the drug dose.^{125 149 168}

• In patients receiving extended-release oral suspension, importance of instructing patients and/or their caregivers on proper use of the dosing dispenser for administration.¹⁵⁷ Provide patient and/or caregiver with a copy of the manufacturer's instructions for administration.¹⁵⁷

• Importance of instructing patients and/or their caregivers regarding application and removal of the transdermal system (see Transdermal Administration under Dosage and Administration).¹⁴⁷ Importance of not touching the adhesive layer during application to avoid absorption of the drug; if contact occurs, wash hands immediately after application.¹⁴⁷

• Inform male patients and their caregivers about the signs and symptoms of priapism, stressing the need for immediate medical treatment if it occurs.^{114 125 145 147 149 151 152 157 158 159 162 168} Younger males, especially prepubertal males, may not recognize the problem or may be embarrassed to tell anyone if it occurs.¹⁵⁹

• Inform patients about the risk of peripheral vascular disorders, including Raynaud's phenomenon, and the associated signs and symptoms (e.g., feelings of numbness, coolness, or pain in fingers or toes; changes in color from pale to blue to red).^{114 125 145 147 149 151 152 157 158 162 168} Advise patients to report any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes and to immediately contact their clinician if any signs of unexplained wounds appear on fingers or toes; further clinical evaluation may be appropriate.^{114 125 145 147 149 151 152 157 158 162 168}

• Importance of monitoring for changes in skin color (depigmentation, hypopigmentation) while receiving transdermal methylphenidate and informing clinician if such changes occur.¹⁶³

• In patients receiving transdermal therapy, importance of not exposing the application site to direct external heat sources (e.g., hair dryers, heating pads, electric blankets, heated water beds) while wearing the system.¹⁴⁷

• Possibility of dermatologic reactions in patients receiving transdermal therapy; importance of discontinuing use and contacting clinician if swelling or blistering occurs.¹⁴⁷

• Importance of informing patients and/or caregivers that methylphenidate is a drug of potential abuse and should be protected from theft or misuse.^{157 168} Importance of properly disposing of the drug when no longer needed.^{157 168}

• Importance of informing clinicians immediately of adverse cardiovascular (e.g., chest pain, shortness of breath, fainting) or psychiatric effects (e.g., hallucinations, delusional thinking, mania).^{114 118 125 147 149 151} Inform patient that the drug can increase BP and pulse rate.^{157 168}

• Importance of taking the drug only as prescribed; importance of not increasing the dosage unless otherwise instructed by a clinician.^{118 125 129}

• Potential for stimulants to impair ability to perform potentially hazardous tasks; use caution when driving or operating machinery until effects on individual are known.^{147 162}

• In patients receiving extended-release trilayer core tablets, presence of tablet-like substance in stool is not cause for concern.¹¹⁸

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products, as well as any concomitant illnesses/conditions (e.g., glaucoma, cardiac/cardiovascular disease, mental/psychiatric disorder, seizures, suicidal ideation or behaviors, history of substance abuse).^{114 118 125 129 147 149 151}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{114 118 125 129 151 158}

• Importance of informing patients of other important precautionary information.^{114 118 125 129 151 158} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.^{114 118 125 129 151 158}

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Frequently asked questions

• Concerta vs Adderall - What's the difference between them?
• Ritalin vs Vyvanse - What's the difference between them?
• What are the brands of methylphenidate?
• How is Cotempla XR-ODT different to other brands of methylphenidate?
• Jornay PM vs other methylphenidate formulations - how do they compare?

Medical Disclaimer