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Methylphenidate Hydrochloride

Pronunciation

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: Concerta, Daytrana, Metadate, Methylin, Ritalin

Warning(s)

Special Alerts:

[Posted 12/17/2013] ISSUE: FDA is warning that methylphenidate products, one type of stimulant drug used to treat attention deficit hyperactivity disorder (ADHD), may in rare instances cause prolonged and sometimes painful erections known as priapism. Based on a recent review of methylphenidate products, FDA updated drug labels and patient Medication Guides to include information about the rare but serious risk of priapism. If not treated right away, priapism can lead to permanent damage to the penis.

Priapism can occur in males of any age and happens when blood in the penis becomes trapped, leading to an abnormally long-lasting and sometimes painful erection. Another ADHD drug, Strattera (atomoxetine), has also been associated with priapism in children, teens, and adults.

Priapism appears to be more common in patients taking atomoxetine than in those taking methylphenidate products; however, because of limitations in available information, FDA does not know how often priapism occurs in patients taking either type of product.

See the FDA Drug Safety Communication for additional information, including a Data Summary

BACKGROUND: Methylphenidate products are central nervous system (CNS) stimulants used to treat attention deficit hyperactivity disorder (ADHD).

RECOMMENDATION: Healthcare professionals should talk to male patients and their caregivers to make sure they know the signs and symptoms of priapism and stress the need for immediate medical treatment should it occur. Younger males, especially those who have not yet reached puberty, may not recognize the problem or may be embarrassed to tell anyone if it occurs.

Encourage your patients to read the Medication Guide they receive with every filled prescription. Use caution when considering switching patients from methylphenidate to atomoxetine. Patients should not stop taking a methylphenidate product without first discussing it with your health care professional.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.

For more information visit the FDA website at: and .

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

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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 orally114 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 therapy125 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 is similar to that of conventional tablets administered at a dosage of 5 mg 3 times daily (given every 4 hours).118

Peak plasma concentrations for transdermal system (Daytrana) are attained within 7.5–10.5 hours.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 long-term administration.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 and extended-release capsules.118 125 126 127 129 130

Food

Administration of chewable tablets 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

Administration of oral solution with high-fat meal delays time to peak plasma concentration by approximately 1 hour and increases average peak plasma concentration and AUC of methylphenidate compared with administration under fasting conditions.145

High-fat meal may alter absorption characteristics of extended-release capsules (Ritalin LA, Metadate CD); opening the capsules and sprinkling the contents on applesauce does not alter bioavailability.125 129

High-fat meal does not alter pharmacokinetics of extended-release trilayer core tablet.118

Distribution

Extent

Extent of distribution in humans is unknown.a

Elimination

Metabolism

Metabolized primarily by de-esterification to form d-ritalinic acid, which has little or no pharmacologic activity.118 125 129 145 147 152

Elimination Route

Excreted as metabolites (principally as ritalinic acid), mostly in urinea b 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 conventional tablets, 2.5 hours in children and 3.5 hours in adults.129

For chewable tablets, 3 hours in adults.152

For oral solution, same as for conventional tablets.145

For extended-release capsules (Metadate CD), 6.8 hours.125

For extended release-capsules (Ritalin LA), 2.4 hours in children and 3.3 hours in adults.129

For extended-release trilayer core tablets, 3.5 hours.118

For transdermal system, approximately 3–4 hours (d-methylphenidate) or 1.4–3 hours (l-methylphenidate).147

Stability

Storage

Oral

Conventional and Extended-release Tablets

Tight, light-resistant containers at 15–30°C.114 b c Protect from moisture.114 b c

Chewable Tablets

Tight containers at 20–25°C.152 Protect from moisture.152

Extended-release Capsules

25°C (may be exposed to 15–30°C).125 129

Extended-release Trilayer Core Tablets

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

Solution

20–25°C.145

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

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

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 Capsules may be opened and the contents sprinkled on applesauce.125 129

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

  • 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

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

  • 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 b c

  • Importance of informing patients of other important precautionary information.114 118 125 129 b c (See Cautions.)

Preparations

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

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.114 118 125 129 b c

Methylphenidate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Transdermal System

10 mg/9 hours (27.5 mg/12.5 cm2)

Daytrana ( C-II)

Shire

15 mg/9 hours (41.3 mg/18.75 cm2)

Daytrana ( C-II)

Shire

20 mg/9 hours (55 mg/25 cm2)

Daytrana ( C-II)

Shire

30 mg/9 hours (82.5 mg/37.5 cm2)

Daytrana ( C-II)

Shire

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

Methylphenidate Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release (containing beads)

10 mg (beads, extended-release 7 mg with 3 mg immediate-release)

Metadate CD ( C-II; with povidone)

UCB

10 mg (beads, extended-release 5 mg with 5 mg immediate-release)

Ritalin LA ( C-II)

Novartis

20 mg (beads, extended-release 14 mg with 6 mg immediate-release)

Metadate CD ( C-II; with povidone)

UCB

20 mg (beads, extended-release 10 mg with 10 mg immediate-release)

Ritalin LA ( C-II)

Novartis

30 mg (beads, extended-release 21 mg with 9 mg immediate-release)

Metadate CD ( C-II; with povidone)

UCB

30 mg (beads, extended-release 15 mg with 15 mg immediate-release)

Ritalin LA ( C-II)

Novartis

40 mg (beads, extended-release 28 mg with 12 mg immediate release)

Metadate CD ( C-II; with povidone)

UCB

40 mg (beads, extended-release 20 mg with 20 mg immediate-release)

Ritalin LA ( C-II)

Novartis

50 mg (beads, extended-release 35 mg with 15 mg immediate-release)

Metadate CD ( C-II; with povidone)

UCB

60 mg (beads, extended-release 42 mg with 18 mg immediate-release)

Metadate CD ( C-II; with povidone)

UCB

Solution

5 mg/5 mL

Methylin ( C-II)

Sciele

10 mg/5 mL

Methylin ( C-II)

Sciele

Tablets

5 mg*

Methylin ( C-II; dye-free)

Mallinckrodt

Methylphenidate Hydrochloride Tablets ( C-II)

Sandoz, UCB, Watson

Ritalin Hydrochloride ( C-II)

Novartis

10 mg*

Methylin ( C-II; dye-free; scored)

Mallinckrodt

Methylphenidate Hydrochloride Tablets ( C-II)

Sandoz, UCB, Watson

Ritalin Hydrochloride ( C-II; scored)

Novartis

20 mg*

Methylin ( C-II; dye-free; scored)

Mallinckrodt

Methylphenidate Hydrochloride Tablets ( C-II)

Sandoz, UCB, Watson

Ritalin Hydrochloride ( C-II; scored)

Novartis

Tablets, chewable

2.5 mg

Methylin ( C-II; with aspartame)

Sciele

5 mg

Methylin ( C-II; with aspartame)

Sciele

10 mg

Methylin ( C-II; scored; with aspartame)

Sciele

Tablets, extended-release

10 mg

Metadate ER ( C-II; dye-free)

UCB

Methylin ER ( C-II; dye-free)

Mallinckrodt

20 mg*

Metadate ER ( C-II; dye-free)

UCB

Methylin ER ( C-II; dye-free)

Mallinckrodt

Methylphenidate Hydrochloride Extended-release Tablets ( C-II)

Sandoz, UCB, Watson

Ritalin-SR ( C-II; with povidone; dye-free)

Novartis

Tablets, extended-release core

18 mg (core 14 mg with 4 mg immediate-release)

Concerta ( C-II; with povidone and propylene glycol; dye-free)

McNeil

27 mg (core 21 mg with 6 mg immediate-release)

Concerta ( C-II; with povidone and propylene glycol; dye free)

McNeil

36 mg (core 28 mg with 8 mg immediate-release)

Concerta ( C-II; with povidone and propylene glycol; dye-free)

McNeil

54 mg (core 42 mg with 12 mg immediate-release)

Concerta ( C-II; with povidone and propylene glycol; dye-free)

McNeil

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Concerta 18MG Controlled-release Tablets (JANSSEN): 20/$129.99 or 30/$194.96

Concerta 27MG Controlled-release Tablets (JANSSEN): 20/$133.99 or 30/$200.98

Concerta 36MG Controlled-release Tablets (JANSSEN): 20/$132.99 or 30/$195.98

Concerta 54MG Controlled-release Tablets (JANSSEN): 20/$144.99 or 30/$211.96

Daytrana 10MG/9HR Patches (NOVEN THERAPEUTICS): 30/$185.98 or 60/$369.96

Daytrana 15MG/9HR Patches (NOVEN THERAPEUTICS): 30/$199.99 or 90/$528.23

Daytrana 20MG/9HR Patches (NOVEN THERAPEUTICS): 30/$185.99 or 60/$359.97

Daytrana 30MG/9HR Patches (NOVEN THERAPEUTICS): 30/$189.00 or 90/$540.98

Metadate CD 10MG Controlled-release Capsules (UCB PHARMA): 20/$98.99 or 30/$148.97

Metadate CD 20MG Controlled-release Capsules (UCB PHARMA): 20/$100.99 or 30/$148.48

Metadate CD 30MG Controlled-release Capsules (UCB PHARMA): 20/$99.99 or 30/$148.48

Metadate CD 60MG Controlled-release Capsules (UCB PHARMA): 20/$162.99 or 30/$244.97

Metadate ER 10MG Controlled-release Tablets (UCB PHARMA): 20/$31.99 or 30/$47.98

Metadate ER 20MG Controlled-release Tablets (UCB PHARMA): 20/$48.99 or 30/$73.97

Methylin 10MG Tablets (MALLINCKRODT PHARM): 20/$13.99 or 30/$20.98

Methylin ER 10MG Controlled-release Tablets (MALLINCKRODT PHARM): 20/$21.99 or 30/$29.98

Methylphenidate HCl 10MG Tablets (MALLINCKRODT): 20/$22.24 or 30/$33.36

Methylphenidate HCl 18MG Controlled-release Tablets (WATSON LABS): 20/$115.99 or 30/$173.98

Methylphenidate HCl 20MG 24-hr Capsules (ACTAVIS SOUTHATLANTIC): 20/$95.99 or 30/$135.97

Methylphenidate HCl 20MG Tablets (MALLINCKRODT): 20/$20.99 or 30/$31.49

Methylphenidate HCl 27MG Controlled-release Tablets (WATSON LABS): 20/$120.99 or 30/$180.97

Methylphenidate HCl 30MG 24-hr Capsules (ACTAVIS SOUTHATLANTIC): 20/$99.99 or 30/$139.97

Methylphenidate HCl 36MG Controlled-release Tablets (WATSON LABS): 20/$120.99 or 30/$179.97

Methylphenidate HCl 40MG 24-hr Capsules (ACTAVIS SOUTHATLANTIC): 20/$95.99 or 30/$139.97

Methylphenidate HCl 5MG Tablets (MALLINCKRODT): 20/$29.99 or 30/$44.99

Methylphenidate HCl 54MG Controlled-release Tablets (WATSON LABS): 20/$130.99 or 30/$194.98

Methylphenidate HCl CR 20MG Controlled-release Tablets (MALLINCKRODT): 20/$35.99 or 30/$53.98

Ritalin 10MG Tablets (NOVARTIS): 20/$29.99 or 30/$41.99

Ritalin 20MG Tablets (NOVARTIS): 20/$42.39 or 30/$63.58

Ritalin 5MG Tablets (NOVARTIS): 20/$41.20 or 30/$61.80

Ritalin LA 10MG 24-hr Capsules (NOVARTIS): 20/$100.99 or 30/$150.97

Ritalin LA 20MG 24-hr Capsules (NOVARTIS): 20/$100.99 or 30/$150.97

Ritalin LA 30MG 24-hr Capsules (NOVARTIS): 20/$100.99 or 30/$150.97

Ritalin LA 40MG 24-hr Capsules (NOVARTIS): 20/$101.98 or 30/$151.97

Ritalin SR 20MG Controlled-release Tablets (NOVARTIS): 20/$59.99 or 30/$85.81

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 2, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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145. Alliant Pharmaceuticals. Methylin (methylphenidate HCl) oral solution prescribing information. Alpharetta, GA. 2006 Feb 28.

146. Novartis. Ritalin LA (methylphenidate hydrochloride) extended-release capsules prescribing information. East Hanover, NJ. 2002 Jun.

147. Shire US Inc. Daytrana (methylphenidate) transdermal system prescribing information. Wayne, PA. 2007 Mar.

148. UCB, Inc. Metadate CD once-daily (methylphenidate HCl) extended-release capsules prescribing information. Smyrna, GA. 2006 May.

149. Novartis. Ritalin LA (methylphenidate hydrochloride) extended-release capsules prescribing information. East Hanover, NJ. 2007 Apr.

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151. Mallinckrodt. Methylin (methylphenidate HCl) tablets and Methylin ER (methylphenidate HCl) extended-release tablets prescribing information. St Louis, MO. 2007 Apr 18.

152. Alliant Pharmaceuticals, Inc. Methylin (methylphenidate HCl) chewable tablets prescribing information. Alpharetta, GA. 2006 Feb 27.

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a. AHFS drug information 2007. McEvoy GK, ed. Methylphenidate hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2485-93.

b. Mallinckrodt Inc. Methylin (methylphenidate HCl) tablets and Methylin ER (methylphenidate HCl) extended-release tablets. St Louis, MO; 2000 Feb.

c. Celltech Pharmaceuticals. Metadate ER (methylphenidate hydrochloride) extended-release tablets. Rochester, NY; 2002 Jun.

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