Methylphenidate Hydrochloride

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

Introduction

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

Uses for Methylphenidate Hydrochloride

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.^{100 101 102 103 104 107 114 115 116 117 118 125 145 147 152}

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 Hydrochloride 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} 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 b c}

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

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

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, Methylin ER, Ritalin–SR)

Swallow tablets whole; do not crush or chew.¹¹⁴

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 b c}

Extended-release Capsules (Metadate CD, Ritalin LA)

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

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

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

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

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] under Dosage and Administration).¹²⁹

Extended-release Trilayer Core Tablets (Concerta)

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] under Dosage and Administration).¹¹⁸

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; do not use if package seal is broken.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

Bathing, swimming, or showering should not affect adherence of a properly applied system.¹⁴⁷ If a system does fall off, apply a new system at a different site, but total recommended wear time remains 9 hours per day.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

Parents or caregiver should be encouraged 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, Methylin ER, Ritalin-SR)

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 b c}

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 (Metadate CD, Ritalin LA)

Oral

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)

Oral

Table 1. Recommended Initial Dosages for Patients Being Switched from Conventional Tablets to Metadate CD Extended-release Capsules126

Previous Dosage (Conventional Tablets)	Initial Dosage (Metadate CD Extended-release Capsules)
10 mg twice daily	20 mg once daily
20 mg twice daily	40 mg once daily

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

Table 2. Recommended Initial Dosages for Patients Being Switched from Conventional or Extended-release Tablets to Ritalin LA Extended-release Capsules129

Previous Dosage	Initial Dosage (Ritalin LA Extended-release Capsules)
Conventional Tablets
5 mg twice daily	10 mg once daily
10 mg twice daily	20 mg once daily
15 mg twice daily	30 mg once daily
20 mg twice daily	40 mg once daily
30 mg twice daily	60 mg once daily
Extended-release Tablets
20 mg daily	20 mg once daily
40 mg daily	40 mg once daily
60 mg daily	60 mg once daily

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 Trilayer Core Tablets (Concerta)

Oral

Initially, 18 mg once daily in the morning.¹¹⁸ If adequate response does not occur, increase dosage at approximately weekly intervals 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.¹¹⁸ 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)

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.¹¹⁸

Table 3. Recommended Initial Dosages for Patients Being Switched from Conventional Tablets to Extended-release Trilayer Core Tablets118

Previous Dosage (Conventional Tablets)	Initial Dosage (Concerta Extended-release Trilayer Core Tablets)
5 mg given 2 or 3 times daily	18 mg once daily
10 mg given 2 or 3 times daily	36 mg once daily
15 mg given 2 or 3 times daily	54 mg once daily

Initial dosage as extended-release trilayer core tablets in patients being switched from conventional tablets should not exceed 54 mg daily.¹¹⁸ Adjust dosage at weekly intervals, up to 72 mg once daily.¹¹⁸ A 27-mg extended-release trilayer core tablet also is available for patients who require a more gradual titration or who cannot tolerate a dosage of 36 mg daily.¹¹⁸

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

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

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

Maximum 60 mg daily.^{114 125 129 152 b c}

Extended-release Trilayer Core Tablets (Concerta)

Initial therapy: Manufacturer recommends 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;¹¹⁸ however, some clinicians state that dosage for children 6–12 years of age may be increased to 72 mg daily.¹²⁷

Switched from other formulations: Maximum 72 mg daily.¹¹⁸

Adults

Narcolepsy

Oral

Maximum 60 mg daily.¹¹⁴

Cautions for Methylphenidate Hydrochloride

Contraindications

• 
  

  Marked anxiety, tension, and agitation.^{114 118 125 129 145 147 152 b c}

  
  


• 
  

  Glaucoma.^{114 118 125 129 145 147 152 b c}

  
  


• 
  

  Motor tics or a family history or diagnosis of Tourette’s syndrome.^{114 118 125 129 145 147 152 b c} 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.^{114 118 129 145 147 152 b c} (See Specific Drugs under Interactions.)

  
  


• 
  

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

  
  

Warnings/Precautions

Warnings

Abuse Potential

Tolerance and psychologic dependence may occur with chronic abuse.^{118 152}

Psychotic episodes can occur, particularly with parenteral abuse.^{118 152}

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

Withdrawal Effects

Abrupt withdrawal following prolonged administration may unmask severe depression as well as the effects of chronic overactivity;¹¹⁴ paranoid and suicidal ideation, dysphoric mood (e.g., depression, irritability, anxiety), fatigue, insomnia or hypersomnia, psychomotor agitation, and disturbed sleep may occur.^a Some manifestations (e.g., depression) may persist for prolonged periods.^a Long-term follow-up may be required.^a

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}

Epidemiologic data suggest a possible association between use of stimulants and sudden unexplained death in healthy children and adolescents.^{153 154 155} FDA unable to conclude that these data affect evaluation of overall risk and benefit of stimulants used to treat ADHD in children and adolescents.¹⁵³ FDA is conducting an ongoing safety review of amphetamines and other stimulants to evaluate possible link between use of these agents and sudden death in children.^{153 154 155} Pediatric patients with ADHD and their parents should avoid discontinuing the child’s use of such stimulants before consulting a clinician.¹⁵³

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}

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}

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}

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.^{114 118 147 148 149 150} 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}

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}

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}

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} 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} 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}

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}

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

Visual Disturbances

Visual disturbances (e.g., difficulty with accommodation, blurred vision) reported with stimulants.^{114 118 125 129 145 147 148 149 150 152}

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

Sensitivity Reactions

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; or eosinophilia reported rarely.^{114 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 if the application site is exposed to direct external heat sources (e.g., 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 b c}

Lactation

Not known whether methylphenidate is distributed into milk; caution advised if used in nursing women.^{114 118 125 129 147}

Pediatric Use

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

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} Epidemiologic data also suggest a possible association between use of stimulants and sudden death in healthy children and adolescents.^{153 154 155} (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

Insomnia, headache, nervousness, abdominal pain, nausea, vomiting, anorexia, weight loss, affect lability, tic.^{118 125 129 145 147 152 b c}

Interactions for Methylphenidate Hydrochloride

Not metabolized by CYP isoenzymes; does not inhibit CYP isoenzymes.¹²⁵

Specific Drugs

Drug	Interaction	Comments
Anticonvulsants (e.g., phenobarbital, phenytoin, primidone)	Possible inhibition of anticonvulsant metabolism114 118 125 129 152	Monitor plasma anticonvulsant concentrations when initiating or discontinuing methylphenidate; reduction of anticonvulsant dosage may be required during concomitant therapy114 118 125 129 145 147 152
Clonidine	Rare cases of serious cardiovascular effects, including death; causality not established114 118 119 120 129 145 147 152
Coumarin anticoagulants (e.g., warfarin)	Possible inhibition of anticoagulant metabolism114 118 125 129 145 147 152	Monitor PT when initiating or discontinuing methylphenidate; reduction of anticoagulant dosage may be required during concomitant therapy114 118 125 129 145 147 152
GI drugs (e.g., antacids, H2receptor antagonists)	Potential for increased gastric pH to alter release characteristics of extended-release capsules (Ritalin LA); clinical importance not established129
Hypotensive agents	Antagonism of hypotensive effect114 a	Use with caution114 a
MAO inhibitors	Potentiation of pressor effects, possible hypertensive crisis114 118 125 129 145 147	Methylphenidate contraindicated in patients currently or recently (i.e., within 14 days) receiving MAO inhibitor114 118 125 129 145 147 152
Pressor agents	Possible increase in hypertensive effects125	Use with caution114 118 125 129 145 147 152
SSRIs	Possible inhibition of antidepressant metabolism118 125 147	Reduction of antidepressant dosage may be required114 118 125 129 145 147
Tricyclic antidepressants (e.g., imipramine, clomipramine, desipramine)	Possible inhibition of antidepressant metabolism114 118 125 129 145 147 152	Reduction of antidepressant dosage may be required114 118 125 129 145 147 152

Methylphenidate Hydrochloride 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}

Peak plasma concentrations for conventional tablets, chewable tablets, or oral solution are attained at approximately 1–2 hours.^{114 145 152} Oral solution and chewable tablets are bioequivalent to conventional tablets.^{145 152}

Peak plasma concentrations for extended-release tablets (Methylin ER, Ritalin-SR) are attained within 4.7 hours in children.^{114 151}

Peak plasma concentrations for extended-release capsules (Metadate CD) are attained at 1.5 hours and again at 4.5 hours after a dose.^{125 126}

Peak plasma concentrations for extended-release trilayer core tablets are attained within 1 hour and again at 6–10 hours.¹¹⁸

Peak plasma concentrations for extended-release tablets (Methylin ER) are attained at about 4.7 hours.^b

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

Relative bioavailability of Ritalin LA extended-release capsules given once daily is similar to that of immediate-release 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 extended-release trilayer core tablets administered at a dosage of 18 mg once daily