Version October 2024
Methylphenidate has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including methylphenidate, can result in overdose and death, and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing methylphenidate, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout methylphenidate treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Dosage guidance:
Dosage form information: Due to pharmacokinetic differences, many products are not bioequivalent and not interchangeable on a mg-per-mg basis; when available, dosing conversion information is provided.
Attention-deficit/hyperactivity disorder (alternative agent (Ref)):
Short-acting immediate release: Chewable tablets, Methylin (oral solution), and Ritalin (tablets): Oral: Initial: 10 to 20 mg/day in 2 divided doses before breakfast and lunch; may increase based on response and tolerability in 5 to 10 mg increments at weekly or greater intervals up to a maximum dose of 60 mg/day in 2 to 3 divided doses (Ref).
Intermediate-acting extended release :
Methylphenidate ER tablets (AB rated generics to Metadate ER or Methylin ER) : Oral: Initial: 10 mg twice daily; may increase dose based on response and tolerability in 10 mg increments at weekly or greater intervals up to a maximum dose of 60 mg/day. Some experts suggest a further increase up to 100 mg/day may be necessary in some patients for optimal response (Ref).
Ritalin SR (tablets) [Canadian product]: Oral: Initial: 20 mg once daily in the morning; may increase dose based on response and tolerability in 10 mg increments at weekly or greater intervals up to a maximum dose of 60 mg/day. Some experts suggest a further increase up to 100 mg/day may be necessary in some patients for optimal response (Ref).
Conversion from IR methylphenidate to methylphenidate ER tablets (AB rated generics to Metadate ER or Methylin ER) or Ritalin SR [Canadian product]: To substitute the intermediate-acting ER formulation for the short-acting IR formulation, the dose of the ER formulation (8-hour duration) should correspond to the total 8-hour IR dose.
Long-acting extended release and transdermal:
Adhansia XR (capsules): Oral: Initial: 25 mg once daily in the morning; may increase dose based on response and tolerability in 10 to 15 mg increments at intervals of ≥5 days up to a maximum dose of 100 mg/day. Doses >85 mg are associated with higher rate of side effects.
Conversion from IR methylphenidate to Adhansia XR: Discontinue previous formulation and titrate using above schedule; do not substitute on a mg-per-mg basis.
Note: Adhansia XR has been discontinued in the United States for >1 year.
Aptensio XR (capsules): Oral: Initial: 10 mg once daily in the morning; may increase dose based on response and tolerability in 10 mg increments at weekly or greater intervals up to a maximum dose of 60 mg/day.
Conversion from other methylphenidate products to Aptensio XR: There are no conversion recommendations in the manufacturer's labeling.
Biphentin [Canadian product] (capsules): Oral: Initial: 10 to 20 mg once daily in the morning; may increase dose based on response and tolerability in 10 mg increments at weekly or greater intervals up to a maximum dose of 80 mg/day.
Conversion from IR methylphenidate to Biphentin: Use equivalent total daily dose (TDD) administered once daily.
Concerta (tablets): Oral: Initial: 18 to 36 mg once daily in the morning; may increase dose based on response and tolerability in increments of 18 mg at weekly or greater intervals up to a maximum dose of 72 mg/day.
Conversion from IR methylphenidate and intermediate-acting ER methylphenidate (eg, AB rated generics to Metadate ER or Methylin ER; Ritalin SR [Canadian product]) to Concerta:
|
IR methylphenidate (current dose) |
Intermediate-acting ER methylphenidate (AB rated generics to Metadate ER or Methylin ER; Ritalin SR [Canadian product]) (current dose)a |
Concerta initial dose |
|---|---|---|
|
a Concerta Canadian product labeling. | ||
|
5 mg 2 to 3 times daily |
20 mg daily |
18 mg once daily in the morning |
|
10 mg 2 to 3 times daily |
40 mg daily |
36 mg once daily in the morning |
|
15 mg 2 to 3 times daily |
60 mg daily |
54 mg once daily in the morning |
|
20 mg 2 to 3 times daily |
-- |
72 mg once daily in the morning |
Daytrana transdermal patch: Topical: Initial: 10 mg patch once daily; apply to hip 2 hours before effect is needed and remove 9 hours after application (eg, 3 hours before bedtime); may increase dose based on response and tolerability to the next transdermal patch dosage at intervals of ≥1 week up to 30 mg/day (Ref). Some patients may require up to 60 mg/day for optimal response (Ref). Patch may be removed before 9 hours if a shorter duration of action is required or if late-day adverse effects appear, or it may be worn for up to 16 hours if extended duration of effects is needed (Ref). Plasma concentrations usually start to decline when the patch is removed but drug absorption may continue for several hours after patch removal.
Conversion from IR methylphenidate or from Concerta (long-acting extended release) to the transdermal patch: Discontinue previous formulation and titrate using above schedule; do not substitute on a mg-per-mg basis per manufacturer's labeling. Alternatively, some clinicians support higher starting patch doses for patients converting from oral methylphenidate doses of >20 mg/day. Approximate equivalent doses, with a 9-hour patch wear time, are as follows below (Ref):
|
Immediate release (mg/day) |
Concerta (mg/day) |
Patch size (Daytrana) |
|---|---|---|
|
15 |
18 |
10 mg (12.5 cm2) |
|
22.5 |
27 |
15 mg (18.75 cm2) |
|
30 |
36 |
20 mg (25 cm2) |
|
45 |
54 |
30 mg (37.5 cm2) |
Foquest [Canadian product] (capsules): Oral: Initial: 25 mg once daily in the morning; may increase dose based on response and tolerability at ≥5-day intervals up to a maximum dose of 100 mg/day.
Conversion from IR, intermediate-acting ER, or long-acting ER methylphenidate to Foquest: Using available Foquest capsule strengths, initiate at a TDD that is close to but does not exceed the current total methylphenidate daily dose; do not substitute on a mg-per-mg basis.
Jornay PM (capsules): Oral: Initial: 20 mg once daily in the evening between 6:30 PM and 9:30 PM (eg, 8:00 PM); may increase dose based on response and tolerability in increments of 20 mg at weekly or greater intervals up to a maximum dose of 100 mg/day.
Conversion from IR methylphenidate to Jornay PM: Discontinue previous formulation and titrate using above schedule; do not substitute on a mg-per-mg basis.
Metadate CD (capsules), QuilliChew ER (chewable tablets), Quillivant XR (oral suspension): Oral: Initial: 20 mg once daily in the morning; may increase dose based on response and tolerability in 10 to 20 mg increments at weekly or greater intervals up to a maximum dose of 60 mg/day. Some experts suggest a further increase up to 100 mg/day with Metadate CD may be necessary in some patients for optimal response (Ref). Note: QuilliChew ER tablets are scored and may be broken in half for 10 mg and 15 mg doses.
Conversion from IR, intermediate-acting ER, or long-acting ER methylphenidate to QuilliChew ER or Quillivant XR: Discontinue previous formulation and titrate using above schedule; do not substitute on a mg-per-mg basis. There are no conversion recommendations in the manufacturer's labeling for Metadate CD.
Relexxii (tablets): Oral: Initial: 18 or 36 mg once daily in the morning; may increase daily dose based on response and tolerability in increments of 18 mg at weekly intervals up to a maximum dose of 72 mg/day.
|
Methylphenidate (current dose) |
Relexxii initial dose |
|---|---|
|
5 mg 2 to 3 times daily |
18 mg once daily in the morning |
|
10 mg 2 to 3 times daily |
36 mg once daily in the morning |
|
15 mg 2 to 3 times daily |
54 mg once daily in the morning |
|
20 mg 2 to 3 times daily |
72 mg once daily in the morning |
Fatigue, severe, cancer related or in palliative care setting (off-label use):
Immediate release (Methylin, Ritalin): Oral: Initial: 5 mg once daily or 5 mg twice daily before breakfast and lunch; may increase dose based on response and tolerability in increments of 5 to 10 mg every 3 days up to a maximum dose of 40 mg/day in divided doses (Ref).
Major depressive disorder (unipolar) in medically ill, palliative care, terminal illness, or elderly patients (monotherapy or adjunctive therapy) (off-label use):
Note: Use as monotherapy only in patients with anticipated short remaining lifetime that would preclude onset of effect of an antidepressant; otherwise use as adjunct to antidepressant.
Immediate release (Methylin, Ritalin): Oral: Initial: 2.5 to 5 mg once daily before breakfast or twice daily before breakfast and lunch; may increase dose based on response and tolerability in increments of 2.5 to 5 mg every 1 to 4 days up to 40 mg/day in divided doses (Ref). Some experts suggest a further increase up to 60 mg/day may be necessary in some patients for optimal response (Ref). Do not use sustained-release product.
Narcolepsy (alternative agent (Ref)):
Immediate release (Methylin, Ritalin): Oral: Initial: 10 mg twice daily before breakfast and lunch; may increase dose based on response and tolerability in increments of 5 to 10 mg at intervals of ≥1 week up to a maximum dose of 60 mg/day in 2 to 3 divided doses with the last dose given no later than about 3:00 PM (Ref).
Intermediate-acting extended release (Methylphenidate ER tablets [AB rated generics to Metadate ER or Methylin ER], Ritalin SR [Canadian product]): Oral: Substitute the intermediate-acting ER formulation in place of the short-acting immediate release when the total 8-hour IR dose corresponds to the ER tablet strength (usually dosed as 20 mg twice daily; duration of action: ~8 hours); maximum: 60 mg/day (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Oral, Transdermal: No dosage adjustment necessary for any degree of kidney impairment; undergoes extensive metabolism to a metabolite with little to no known pharmacologic or toxic effects (Ref).
Intermittent hemodialysis (thrice weekly): Oral, Transdermal: Unlikely to be significantly dialyzed (large Vd): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Oral, Transdermal: Unlikely to be significantly dialyzed (large Vd): No dosage adjustment necessary (Ref).
CRRT: Oral, Transdermal: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral, Transdermal: No dosage adjustment necessary (Ref).
Oral: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Transdermal: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Methylphenidate: Pediatric drug information")
Attention-deficit/hyperactivity disorder (ADHD): Methylphenidate is recommended as first-line therapy for children and adolescents; dosage should be individualized; a discontinuation trial after 6 months of therapy is also recommended to reassess underlying psychopathology (Ref). Note: Discontinue medication if no improvement is seen after appropriate dosage adjustment over a 1-month period of time.
Due to pharmacokinetic differences, many products are not bioequivalent and not interchangeable on a mg per mg basis; when available, dosing conversion information is provided. Presented maximum doses are primarily based on manufacturer's labeling from clinical trials, however, higher maximum doses from guidelines are also included; dose titration should be optimized for efficacy and tolerability (Ref).
Oral:
Immediate-release products (eg, Methylin, Ritalin):
Children 3 to 5 years, moderate to severe dysfunction: Limited data available (Ref):
Note: AAP considers first-line agent in this patient population if pharmacological treatment deemed necessary (Ref); the AACAP Preschool Psychopharmacology Working Group recommends a discontinuation trial after 6 months of treatment in preschoolers to reassess underlying psychopathology (Ref). Response may be variable and less robust than that observed in older pediatric patients (Ref); of note, response to methylphenidate was predicted by the number of comorbidities (eg, no or 1 comorbidity predicted a large treatment response [similar to school-aged children] vs ≥3 comorbidities predicted no treatment response) (Ref).
Initial: 2.5 mg twice daily, may gradually titrate to 7.5 mg 2 or 3 times daily over 2 to 4 weeks; others have used a rapid titration to 7.5 mg 3 times daily within 1 week (Ref); a small percentage of preschool children may benefit from 1.25 mg 3 times daily (Ref). In the largest trial, a multicenter, randomized, placebo-controlled, crossover study of 165 preschool children (age range: 3 to 5.5 years) treated with methylphenidate 3.75 to 30 mg/day in 3 divided doses, statistically and clinically significant improvements in ADHD scores were reported with doses of 2.5 mg, 5 mg, and 7.5 mg 3 times daily. In some patients (n=7 [4%]), dose titration to 10 mg 3 times daily was necessary; the mean effective total daily dose: 14.2 ± 8.1 mg/day. Although ADHD scores were statistically and clinically improved with methylphenidate use, the effect size was smaller with this younger patient population than that seen in school-age children (Ref). The 10-month continuation phase trial reported continued or stable clinical improvement at a mean dose of 19.98 mg/day at month 10 (Ref).
Children ≥6 years and Adolescents: Initial: 2.5 to 5 mg twice daily administered before breakfast and lunch; increase by 5 to 10 mg/day at weekly intervals; some patients may require 3 doses/day (eg, additional dose after school); usual maximum daily dose: 60 mg/day, not to exceed 2 mg/kg/day; however, some patients weighing >50 kg may require and tolerate daily doses up to 100 mg/day with frequent monitoring (Ref).
Extended-release, sustained-release, and long-acting products:
Adhansia XR: Children ≥6 years and Adolescents: Initial: 25 mg once daily in the morning; may titrate in 10 to 15 mg increments at ≥5-day intervals; maximum daily dose: 85 mg/day; doses ≥70 mg/day, although efficacious, were associated with disproportionate increase in adverse reaction; monitor tolerability closely in these patients. To convert from other methylphenidate products, discontinue that treatment and begin Adhansia XR with titration schedule previously described. Note: Adhansia XR has been discontinued in the United States for >1 year.
Aptensio XR: Children ≥6 years and Adolescents: Initial: 10 mg once daily in the morning; may titrate in 10 mg increments at weekly intervals; maximum daily dose: 60 mg/day.
Concerta: Children ≥6 years and Adolescents:
Methylphenidate-naive patients: Initial: 18 mg once daily.
Patients currently using immediate-release methylphenidate: Initial dose: Dosing based on current regimen and clinical judgment; suggested dosing listed below, monitor closely with any therapy change:
Switching from methylphenidate immediate release 5 mg 2 to 3 times daily: Concerta 18 mg once daily.
Switching from methylphenidate immediate release 10 mg 2 to 3 times daily: Concerta 36 mg once daily.
Switching from methylphenidate immediate release 15 mg 2 to 3 times daily: Concerta 54 mg once daily.
Switching from methylphenidate immediate release 20 mg 2 to 3 times daily: Concerta 72 mg once daily.
Dosage adjustment: May increase by Concerta 18 mg/day increments at weekly intervals to effect not to exceed the following maximum daily dose for age. Note: A dosage strength of 27 mg is available for situations in which a dosage between 18 and 36 mg is desired.
Maximum daily dose of Concerta:
Children 6 to 12 years: Usual maximum daily dose: 54 mg/day; however, some patients may require and tolerate daily doses up to 108 mg/day (Ref).
Adolescents: Usual maximum daily dose: 72 mg/day; however, some patients may require and tolerate daily doses up to 108 mg/day (Ref).
Cotempla XR-ODT: Children ≥6 years and Adolescents ≤17 years: Initial: 17.3 mg once daily in the morning; may titrate in 8.6 or 17.3 mg increments at weekly intervals; maximum daily dose: 51.8 mg/day.
Jornay PM: Children ≥6 years and Adolescents: Initial: 20 mg once daily in the evening between 6:30 and 9:30 PM (eg, 8:00 PM); may increase in increments of 20 mg/day at weekly intervals; maximum daily dose: 100 mg/day. Note: If converting from another methylphenidate formulation, discontinue previous formulation and titrate Jornay PM using above schedule; do not substitute on a milligram-per-milligram basis.
Metadate ER, Ritalin-SR: Children ≥6 years and Adolescents: Replace immediate-release tablets when the 8-hour dosage corresponds to sustained-/extended-release tablet size; Ritalin SR may be administered once or twice daily (Ref). Usual maximum daily dose: 60 mg/day; however, some patients weighing >50 kg may require and tolerate daily doses up to 100 mg/day with frequent monitoring (Ref).
Methylphenidate extended-release capsules (eg, generic Metadate CD): Children ≥6 years and Adolescents: Limited data available in ages >15 years: Initial: 20 mg once daily; may increase by 10 to 20 mg/day increments at weekly intervals; usual maximum daily dose: 60 mg/day; however, some patients weighing >50 kg may require and tolerate daily doses up to 100 mg/day with frequent monitoring (Ref).
QuilliChew ER: Children ≥6 years and Adolescents: Initial: 20 mg once daily in the morning; may be adjusted in 10, 15, or 20 mg increments at weekly intervals (tablets are scored and may be broken in half to achieve dose); maximum daily dose: 60 mg/day. Note: If converting from another methylphenidate formulation, discontinue previous formulation and titrate QuilliChew ER using above schedule; do not substitute on a milligram-per-milligram basis.
Quillivant XR: Children ≥6 years and Adolescents: Initial: 20 mg once daily in the morning; may increase by 10 to 20 mg/day increments at weekly intervals; maximum daily dose: 60 mg/day.
Relexxii:
Methylphenidate-naive patients:
Children ≥6 to ≤12 years: Initial: 18 mg once daily in the morning; may increase by 18 mg increments at weekly intervals up to 54 mg once daily; higher doses have not been studied. Note: Available in 27 mg, 45 mg, and 63 mg strengths for additional titration options.
Adolescents <18 years: Initial: 18 mg once daily in the morning; may increase by 18 mg increments at weekly intervals up to 72 mg once daily or 2 mg/kg/day, whichever is lower; higher doses have not been studied. Note: Available in 27 mg, 45 mg, and 63 mg strengths for additional titration options.
Adolescents ≥18 years: Initial: 18 mg or 36 mg once daily in the morning; may increase by 18 mg increments at weekly intervals up to a maximum daily dose: 72 mg/day. Note: Available in 27 mg, 45 mg, and 63 mg strengths for additional titration options.
Patients currently receiving immediate-release methylphenidate:
Children ≥6 years and Adolescents:
|
Current Methylphenidate IR Total Daily Dose |
Relexxii Starting Dose |
|---|---|
|
10 to 15 mg/day |
18 mg once daily |
|
20 to 30 mg/day |
36 mg once daily |
|
30 to 45 mg/day (eg, 15 mg 2 or 3 times daily) |
54 mg once daily |
|
40 to 60 mg/day (eg, 20 mg 2 or 3 times daily) |
72 mg once daily |
Ritalin LA: Children ≥6 years and Adolescents:
Methylphenidate-naive patients: Initial: 20 mg once daily; may increase by 10 mg/day increments at weekly intervals; usual maximum daily dose: 60 mg/day; however, some patients weighing >50 kg may require and tolerate daily doses up to 100 mg/day with frequent monitoring (Ref). Note: If a lower initial dose is desired, patients may begin with Ritalin LA 10 mg once daily. Alternatively, patients may begin therapy with an immediate-release product, and switch to Ritalin LA once immediate-release dosage is titrated to 5 mg twice daily (see below).
Patients currently receiving immediate-release methylphenidate: The same total daily dose of Ritalin LA should be used.
Patients currently receiving methylphenidate sustained release (SR): The same total daily dose of Ritalin LA should be used.
Canadian labeling:
Concerta: Children ≥6 years and Adolescents:
Sustained-release methylphenidate [Canadian product] to Concerta: Oral:
Switching from methylphenidate SR 20 mg daily: Concerta 18 mg once every morning.
Switching from methylphenidate SR 40 mg daily: Concerta 36 mg once every morning.
Switching from methylphenidate SR 60 mg daily: Concerta 54 mg once every morning.
Biphentin [Canadian product]: Children ≥6 years and Adolescents:
Methylphenidate-naive patients: Oral: Initial: 10 to 20 mg once daily; may be adjusted in 10 mg increments at weekly intervals; maximum daily dose: 60 mg/day. Note: In some children and adolescents, higher doses may be necessary; do not exceed 1 mg/kg/day or the adult maximum of 80 mg/day; monitor closely for adverse events, reduce dose or discontinue if adverse events occur.
Patients currently receiving immediate-release methylphenidate: Use equivalent total daily dose administered once daily.
Foquest [Canadian product]: Children ≥6 years and Adolescents:
Methylphenidate-naive patients: Oral: Initial: 25 mg once daily; may be adjusted by 10 to 15 mg/day increments (based on available dosage forms) at ≥5-day intervals; maximum daily dose: 70 mg/day for patients <18 years of age; 100 mg/day for patients ≥18 years of age.
Patients currently receiving immediate-release methylphenidate: Calculate the patient's total daily methylphenidate dose and begin patient on the next lower strength.
Topical: Transdermal patch (Daytrana): Children and Adolescents 6 to 17 years: Initial: 10 mg (12.5 cm2) patch once daily; apply to hip 2 hours before effect is needed and remove 9 hours after application (eg, 3 hours before bedtime); titrate dose based on response and tolerability; may increase to next transdermal patch dosage size no more frequently than every week. Patch may be removed before 9 hours if a shorter duration of action is required or if late day adverse effects appear or may be worn for up to 16 hours if extended duration of effects are needed (Ref). Plasma concentrations usually start to decline when the patch is removed but drug absorption may continue for several hours after patch removal. Note: The manufacturer's labeling recommends that patients converting from another formulation of methylphenidate to the transdermal patch should be initiated at 10 mg regardless of their previous dose and titrated as needed due to the differences in bioavailability of the transdermal formulation. However, some clinicians have supported higher starting patch doses for patients converting from oral methylphenidate doses of >20 mg/day; for example, the 15 mg (18.75 cm2) patch has been investigated to have the same effect as 22.5 mg daily of the immediate-release preparation, 27 mg daily of the osmotic-release preparation (Concerta), or 20 mg daily of the encapsulated bead preparation (eg, generic Metadate CD) (Ref).
Approximate oral methylphenidate equivalents, with a 9-hour patch wear time, for the 20 mg and 30 mg patches are (Ref):
|
Approximate oral equivalent daily dose | ||
|---|---|---|
|
Patch size (eg, Daytrana) |
Immediate release (mg/day) |
Osmotic release tablet (eg, Concerta) (mg/day) |
|
15 mg (18.75 cm2) |
22.5 mg/day |
27 mg/day |
|
20 mg (25 cm2) |
30 mg/day |
36 mg/day |
|
30 mg (37.5 cm2) |
45 mg/day |
54 mg/day |
Narcolepsy: Children ≥6 years and Adolescents: Oral:
Immediate-release tablets and oral solution (Methylin, Ritalin): Initial: 5 mg twice daily given before breakfast and lunch; increase by 5 to 10 increments mg/day at weekly intervals; 2 to 3 times per day; maximum daily dose: 60 mg/day (in 2 to 3 divided doses).
Extended-/sustained-release tablets (Metadate ER, Ritalin-SR): May be given in place of immediate-release products, once the immediate-release formulation daily dose is titrated and the titrated 8-hour dosage corresponds to sustained- or extended-release tablet size; maximum daily dose: 60 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Oral: There are no dosage adjustments provided in manufacturer's labeling (has not been studied); undergoes extensive metabolism to a renally eliminated metabolite with little or no pharmacologic activity.
Transdermal: There are no dosage adjustments provided in manufacturer's labeling (has not been studied).
Oral, Transdermal: There are no dosage adjustments provided in manufacturer's labeling (has not been studied).
Cardiovascular events, including acute myocardial infarctions [MI], sudden cardiac death, stroke, tachycardia, and increased blood pressure, have been reported in adult and pediatric patients (Ref). Methylphenidate, similar to other CNS stimulants, has been associated with sudden death in children and adolescents with preexisting structural cardiac abnormalities. Available data in patients without congenital heart disease are conflicting (Ref). A large retrospective cohort study showed an overall low incidence and risk of serious cardiovascular events in children and young adults (Ref); similarly, retrospective claims databases have not shown an increase in serious cardiovascular events (MI, sudden death, stroke) with stimulant use in young and middle-aged adults (Ref).
Mechanism: Methylphenidate increases the mean heart rate and systolic blood pressure by mediating the sympathetic, central and peripheral catecholaminergic systems (Ref). This increase in heart rate and blood pressure can ultimately lead to cardiovascular events such as arrhythmias and/or MI.
Onset: Increased risk for MI appeared after 1 week of treatment and persisted over 2 months. Arrhythmias and hypertension were reported to be more immediate adverse effects (day 1 to 3) and (day 4 to 7) after initiation of treatment respectively (Ref).
Risk factors:
• Patients with prior structural heart disease (Ref)
• Concomitant use of QTc prolonging medications may increase the risk of arrhythmias
Some studies have reported growth retardation in pediatric patients. Decreased height and weight changes have been described in children <12 years receiving long-term treatment (ie, ≥3 years) (Ref). Similarly, statistically significant reductions in total femoral, femoral neck, and lumbar bone mineral density (BMD) were observed in pediatric patients (age range: 8 to 17 years) actively treated with stimulants (including but not limited to methylphenidate) when compared to matched unmedicated controls; also reported were significantly more subjects in the stimulant-treated group with BMD measurements in the osteopenic range compared to matched controls (38.3% to 21.6%) (Ref). An association has been observed between cumulative methylphenidate exposure in childhood and decreased height velocity, decreased adult height, and increased weight in adulthood (Ref). In contrast, a longitudinal cohort-controlled trial reported no difference in peak height velocity and final adult height in subjects with ADHD and/or treated with stimulants (Ref). In adults, methylphenidate has been shown to cause anorexia with weight loss (Ref).
Mechanism: Possibly due to effects on central nervous system growth factors and hepatic growth factors and direct cartilage effects. Weight loss may result from appetite suppression, reduced food intake, increased activity, and metabolic shifts (Ref).
Onset: Growth suppression in children: Delayed; appears to occur after months of active treatment (Ref). Appetite suppression in adults: Immediate; occurs within hours of initiation of therapy and after only one dose (Ref).
Risk factors:
• Duration of treatment/cumulative methylphenidate exposure (Ref)
Priapism associated with neurostimulants like methylphenidate has been reported in the literature and published in an FDA Drug Safety Communication. The presentation of priapism has ranged in severity, occurred with dose changes and withdrawal of the medication, and has been reported with different dosage forms and products (Ref). The overall incidence of methylphenidate-induced priapism is unknown. In severe cases, priapism (ischemic) can be a urological emergency and may require surgical interventions to prevent permanent erectile dysfunction, fibrosis, and impotence.
Mechanism: Prolonged erections occur when the balance of the smooth muscle cell (SMC) control system is altered towards SMC relaxation; ischemic priapism results when the inflow and outflow of blood is halted (Ref).
Onset: Rapid; may be related to the half-life of the medication/formulation. Case reports have reported onset of priapism within a few hours of ingesting immediate-release methylphenidate or the day after taking sustained release methylphenidate (Ref).
Risk factors:
• Hematological dyscrasias (eg, sickle cell disease) (Ref)
• Malignancies (Ref)
• Perineal trauma (Ref)
• Alcohol use (Ref)
• Concomitant use of illicit drugs known to cause priapism (eg, cocaine, ecstasy, marijuana) (Ref)
• Concomitant use of prescription medications associated with priapism (eg, psychotropic medications [typical and atypical antipsychotics, antidepressants, and anxiolytics], alpha-adrenergic agents, anticoagulants) (Ref)
New-onset psychosis or mania and exacerbation of psychotic or manic symptoms (eg, delusional thinking, auditory hallucination and visual hallucination, mania) may occur with neurostimulant use in all ages; methylphenidate has also been associated with aggressive behavior or hostility in children; however, a causal relationship has not been established (Ref). A recent cohort study in adolescents and young adults failed to show any evidence that the initiation of methylphenidate increased the risk of psychosis (Ref). Patients with ADHD are at increased risk for suicidal ideation and suicide attempt; however, neither increased risk nor a causal relationship with methylphenidate and attempted suicide has been observed in large cohort trials (Ref). The risk of psychosis may be lower with methylphenidate compared to amphetamine products (Ref).
Mechanism: Psychosis: Central stimulants amplify neuronal signaling by increasing in dopamine concentration in the prefrontal cortex of the brain. Increased dopamine levels have been associated with the development of psychotic and manic symptoms (Ref).
Onset: Days to weeks (Ref).
Risk factors:
• Preexisting history of psychosis (Ref)
• Family history of mood and psychotic disorders (eg, major depression, bipolar disorder, schizophrenia) (Ref)
• Young age (children, adolescents, and young adults) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Decreased appetite (2% to 26%), nausea (2% to 13%), xerostomia (oral: 3% to 14%)
Nervous system: Headache (2% to 22%, including migraine; tension headache: oral: 1%), insomnia (including initial insomnia; oral: 2% to 33%; transdermal: 6% to 13%), irritability (2% to 11%)
1% to 10%:
Cardiovascular: Increased blood pressure (≥2%), increased diastolic blood pressure (oral: 7%), palpitations (3%), tachycardia (oral: 5%; transdermal: ≤1%) (table 1)
|
Drug (Methylphenidate) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Methylphenidate) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
1% |
0% |
Children |
N/A |
Transdermal patch |
Attention deficit hyperactivity disorder |
98 |
85 |
|
0.7% |
0% |
Adolescents |
N/A |
Transdermal patch |
Attention deficit hyperactivity disorder |
145 |
72 |
|
5% |
0% |
Adults |
N/A |
Extended-release tablets |
Attention deficit hyperactivity disorder |
415 |
212 |
Dermatologic: Excoriation of skin (oral: 4%), hyperhidrosis (oral: 5%), skin rash (oral: 2%)
Endocrine & metabolic: Decreased libido (oral: 2%), weight loss (2% to 9%) (table 2)
|
Drug (Methylphenidate) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Methylphenidate) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
9% |
0% |
Children |
N/A |
Transdermal patch |
Attention deficit hyperactivity disorder |
98 |
85 |
|
2% |
0% |
Children |
20 to 60 mg/day |
Extended-release chewable tablets |
Attention deficit hyperactivity disorder |
42 |
44 |
|
7% |
0% |
Adolescents |
25 to 85 mg/day |
Extended-release capsules |
Attention deficit hyperactivity disorder |
293 |
74 |
|
6% |
1% |
Adolescents |
N/A |
Transdermal patch |
Attention deficit hyperactivity disorder |
145 |
72 |
|
7% |
3% |
Adults |
N/A |
Extended-release tablets |
Attention deficit hyperactivity disorder |
415 |
212 |
|
4% |
1% |
Adults |
25 to 100 mg/day |
Extended-release capsules |
Attention deficit hyperactivity disorder |
297 |
78 |
Gastrointestinal: Abdominal pain (5% to 7%), anorexia (2% to 9%), bruxism (oral: 2%), constipation (oral: 1%), diarrhea (oral: 4%), dyspepsia (oral: 2%), motion sickness (oral: 2%), upper abdominal pain (oral: 4% to 9%), vomiting (2% to 10%)
Genitourinary: Dysmenorrhea (oral: 2%)
Hematologic & oncologic: Bruise (oral: 3%)
Nervous system: Aggressive behavior (oral: 2%) (table 3), agitation (oral: 2%), anxiety (oral: 8%), confusion (oral: 1%), depressed mood (oral: 4%), depression (2%), dizziness (2% to 7%), emotional lability (1% to 9%), fatigue (3%), hypertonia (oral: 2%), jitteriness (oral: 4%), lack of emotion (oral: 2%), nervousness (3%) paresthesia (1%), psychomotor agitation (oral: 5%), restlessness (oral: 3%), sedated state (oral: 1%), tension (oral: 1%), tic disorder (1% to 9%), tremor (oral: 3%), vertigo (oral: 2%)
|
Drug (Methylphenidate) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Methylphenidate) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
2% |
0% |
Children |
20 to 60 mg/day |
Extended-release chewable tablets |
Attention deficit hyperactivity disorder |
42 |
44 |
|
2% |
0.5% |
Adults |
N/A |
Extended-release tablets |
Attention deficit hyperactivity disorder |
415 |
212 |
Neuromuscular & skeletal: Back pain (oral: 3%)
Ophthalmic: Blurred vision (2%), eye pain (oral: 2%)
Respiratory: Cough (oral: 2%), nasopharyngitis (oral: 3%), oropharyngeal pain (oral: 1% to 2%), streptococcal pharyngitis (oral: 3%), upper respiratory tract infection (oral: 2%)
Miscellaneous: Fever (oral: 2%)
<1%: Dermatologic: Contact hypersensitivity (transdermal)
Frequency not defined:
Cardiovascular: Heart murmur, hypertension
Dermatologic: Macular eruption
Endocrine & metabolic: Hot flash, increased thirst
Gastrointestinal: Abdominal distress, viral gastroenteritis
Genitourinary: Erectile dysfunction, hematuria
Hematologic & oncologic: Anemia, leukopenia
Hepatic: Increased serum alanine aminotransferase
Infection: Viral infection
Nervous system: Delirium, drug abuse, drug dependence, Gilles de la Tourette syndrome, hypervigilance, lethargy, outbursts of anger, panic attack, toxic psychosis
Neuromuscular & skeletal: Muscle cramps, muscle spasm
Ophthalmic: Dry eye syndrome
Respiratory: Bronchitis, dyspnea, sinusitis
Miscellaneous: Drug tolerance
Postmarketing:
Cardiovascular: Acute myocardial infarction (Thompson 2010), angina pectoris, bradycardia, cardiac arrhythmia (Shin 2016), cardiomyopathy (Nymark 2008), chest discomfort, chest pain, extrasystoles, necrotizing angiitis, peripheral vascular insufficiency, Raynaud disease (Goldman 2008), supraventricular tachycardia, syncope (Ferahkaya 2022), ventricular arrhythmia (Schelleman 2012), ventricular premature contractions
Dermatologic: Alopecia (Ardic 2017), bullous skin disease, erythema multiforme, erythema of skin, exfoliative dermatitis, fixed drug eruption (Cohen 1992), leukoderma (transdermal: chemical) (Cheng 2017; FDA Safety Alert 2015), pruritus (Storebø 2018), urticaria (Storebø 2018)
Endocrine & metabolic: Growth retardation (Poulton 2016; Storebø 2015), gynecomastia (Ensat 2012), heavy menstrual bleeding (Özdağ 2022)
Genitourinary: Priapism (Eiland 2014)
Hematologic & oncologic: Immune thrombocytopenia (Grossman 1985), pancytopenia, thrombocytopenia (Ercan 2017)
Hepatic: Autoimmune hepatitis (Lewis 2007), hepatic failure (acute), increased serum bilirubin
Hypersensitivity: Anaphylaxis, angioedema (Goyal 2015)
Local: Application-site reaction (transdermal)
Nervous system: Abnormal behavior, asthenia (Storebø 2018), auditory hallucination (Mosholder 2009), cerebral arteritis (Storebø 2018), disorientation, drowsiness (Storebø 2018), extrapyramidal reaction, hyperactive behavior, hyperpyrexia, hypomania (Storebø 2018), mania (Mosholder 2009), mood changes (Storebø 2018), obsessive compulsive disorder, psychosis (Storebø 2018), seizure (Andrade 2020), sleep disorder (Storebø 2018), talkativeness (Storebø 2018), visual hallucination (Mosholder 2009)
Neuromuscular & skeletal: Arthralgia, dyskinesia (including choreiform movements) (Storebø 2018), dystonia (Uzun 2018), muscle twitching, myalgia, rhabdomyolysis
Ophthalmic: Diplopia, mydriasis
Otic: Swelling of the ear
Respiratory: Epistaxis (Chandradasa 2019)
US labeling: Hypersensitivity (eg, angioedema, anaphylaxis) to methylphenidate or any component of the formulation (including film backing and adhesives for transdermal product); use during or within 14 days following MAOI therapy.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Additional contraindications:
Metadate CD: Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase insufficiency.
Canadian labeling: Hypersensitivity to methylphenidate or any component of the formulation; marked anxiety, tension, and agitation; glaucoma; use during or within 14 days following monoamine oxidase inhibitor therapy; family history or diagnosis of Tourette syndrome or tics (excluding Concerta); thyrotoxicosis; advanced arteriosclerosis; symptomatic cardiovascular disease; moderate to severe hypertension; history of drug abuse (excluding Concerta).
Additional contraindications:
Foquest: Known hypersensitivity or idiosyncrasy to sympathomimetic amines; history of drug abuse.
Ritalin and Ritalin SR: Pheochromocytoma.
Concerns related to adverse effects:
• Ocular effects: Acute angle closure glaucoma and increased intraocular pressure (IOP) have been reported with treatment. Evaluation by an ophthalmologist prior to treatment is recommended in patients at risk for acute angle closure glaucoma (eg, patients with significant hyperopia); use in patients with open angle glaucoma or increased IOP only if benefits outweigh risks.
• Peripheral vasculopathy: Stimulants are associated with peripheral vasculopathy, including Raynaud phenomenon; signs/symptoms are usually mild and intermittent, and generally improve with dose reduction or discontinuation. Peripheral vasculopathy effects have been observed at different times, at therapeutic doses, and in all age groups. Digital ulceration and/or soft tissue breakdown have been observed; further evaluation (eg, rheumatology) may be necessary in patients developing signs and symptoms of peripheral vasculopathy.
• Visual disturbance: Difficulty in accommodation and blurred vision have been reported with the use of stimulants.
Disease-related concerns:
• Bipolar disorder: May precipitate a mixed or manic episode in patients with bipolar illness.
• Cardiovascular disorders: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; may lower seizure threshold leading to new onset or breakthrough seizure activity. Discontinue in the presence of seizures.
• Tourette syndrome/tics: Use with caution in patients with Tourette syndrome or other tic disorders. Stimulants may exacerbate tics (motor and phonic) and Tourette syndrome; however, evidence demonstrating increased tics is limited. Evaluate for tics and Tourette syndrome prior to therapy initiation; use is contraindicated with some products.
Dosage form specific issues:
• Adhansia XR: 45 mg capsules contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Biphentin, Foquest [Canadian products]: Controlled-release capsules are not interchangeable with other controlled-release formulations.
• Concerta, Relexxii: Should not be used with preexisting severe gastrointestinal narrowing conditions, such as esophageal motility disorders, small bowel disease, “short” gut syndrome, cystic fibrosis, history of peritonitis, chronic intestinal pseudo-obstruction, or Meckel diverticulum.
• Daytrana: Transdermal system may cause dermal reactions: Chemical leukoderma and contact sensitization; in a one-year tolerability study, the majority of subjects who withdrew (7%) did so due to dermal reactions (Findling 2009). Chemical leukoderma is a persistent loss of skin pigmentation at and around the application site, as well as at distant sites from the application site, that may resemble vitiligo, especially if loss of skin pigmentation occurs at areas distant from application site; patients with a personal and/or family history of vitiligo may be at more risk; patients should monitor for signs of skin depigmentation and immediately inform their health care provider if observed; discontinue use if patient experiences chemical leukoderma; loss of skin pigmentation may continue after discontinuation. Contact sensitization is characterized by erythema plus an intense local reaction (eg, edema, papules, vesicles) that does not improve within 48 hours or spreads beyond the patch site; sensitization may subsequently manifest systemically with other routes of methylphenidate administration; if using oral methylphenidate, initiate under medical supervision and monitor closely, as some sensitized patients may not be able to take methylphenidate in any form. Avoid exposure of application site to any direct external heat sources (eg, hair dryers, heating pads, electric blankets) while wearing patch; heat may increase the rate and extent of absorption more than 2-fold and result in overdose.
• Lactose/sucrose: Some dosage forms may contain lactose or sucrose; use with caution in patients intolerant to either component (some manufacturer labels recommend avoiding use in such patients).
• Phenylketonuria: Some dosage forms contain phenylalanine, which can be harmful to patients with phenylketonuria. Before prescribing, consider the combined daily amount of phenylalanine from all sources.
Other warnings/precautions:
• ADHD treatment: Appropriate use: Recommended to be used as part of a comprehensive treatment program for attention deficit disorders.
Use with caution in preschool-age children; some clinical trials have reported higher rates of adverse events in children 3 to 5 years of age, compared with older children, and some trials have noted a greater discontinuation of therapy compared to school-age children, though adverse event reports may have been a proxy for inefficacy, rebound, or other underlying causes (Greenhill 2006; Wigal 2006). Although efficacious (Childress 2020; Childress 2022), the 12-month open-label phase of a previous multicenter placebo-controlled trial using the extended-release tablet (Aptensio XR) reported half (n=20/39) of patients 4 to <6 years of age experienced enough lost weight to decrease ≥10 percentiles on CDC growth charts; systemic exposure (AUC, Cmax) was also reported to be 2 to 3 times higher than older children and adolescents (same dose) (manufacturer's labeling).
Adhansia XR has been discontinued in the United States for >1 year.
Aptensio XR capsules contain multi layered beads. The immediate release layer delivers approximately 40% of the methylphenidate dose, and the controlled release layer delivers approximately 60% of the methylphenidate dose.
Concerta is an osmotic controlled release formulation (OROS) of methylphenidate. The tablet has an immediate-release overcoat providing an initial dose of methylphenidate within 1 hour, and the remaining is released at a controlled rate over 5-9 hours. The overcoat covers a trilayer core. The trilayer core is composed of two layers containing the drug and excipients, and one layer of osmotic components. As water from the gastrointestinal tract enters the core, the osmotic components expand and methylphenidate is released.
Metadate CD contains a mixture of immediate release and extended release beads, designed to release 30% of the dose immediately and 70% over an extended period.
Ritalin LA uses Spheroidal Oral Drug Absorption System (SODAS) design to deliver a bimodal release of medication, intended to mimic twice-daily administration of immediate-release methylphenidate. Fifty percent of the drug is delivered in immediate-release beads, and the remaining half is delivered in delayed-release beads approximately 4 hours after administration.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Extended Release, Oral, as hydrochloride:
Metadate CD: 10 mg, 20 mg, 30 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Metadate CD: 40 mg
Metadate CD: 50 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Metadate CD: 60 mg
Generic: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg
Capsule Extended Release 24 Hour, Oral, as hydrochloride:
Adhansia XR: 25 mg [DSC] [contains fd&c blue #1 (brilliant blue)]
Adhansia XR: 35 mg [DSC] [contains fd&c yellow #6 (sunset yellow)]
Adhansia XR: 45 mg [DSC] [contains fd&c yellow #5 (tartrazine)]
Adhansia XR: 55 mg [DSC] [contains fd&c blue #1 (brilliant blue)]
Adhansia XR: 70 mg [DSC], 85 mg [DSC]
Aptensio XR: 10 mg [contains fd&c blue #1 (brilliant blue)]
Aptensio XR: 15 mg [contains fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10)]
Aptensio XR: 20 mg [contains quinoline yellow (d&c yellow #10)]
Aptensio XR: 30 mg [contains fd&c blue #1 (brilliant blue)]
Aptensio XR: 40 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Aptensio XR: 50 mg [contains quinoline yellow (d&c yellow #10)]
Aptensio XR: 60 mg
Jornay PM: 20 mg, 40 mg, 60 mg, 80 mg, 100 mg [contains fd&c blue #1 (brilliant blue)]
Ritalin LA: 10 mg, 20 mg, 30 mg, 40 mg
Generic: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg
Patch, Transdermal:
Daytrana: 10 mg/9 hr (1 ea, 30 ea); 15 mg/9 hr (1 ea, 30 ea); 20 mg/9 hr (1 ea, 30 ea); 30 mg/9 hr (30 ea)
Generic: 10 mg/9 hr (1 ea, 30 ea); 15 mg/9 hr (1 ea, 30 ea); 20 mg/9 hr (1 ea, 30 ea); 30 mg/9 hr (1 ea, 30 ea)
Solution, Oral, as hydrochloride:
Methylin: 5 mg/5 mL (500 mL); 10 mg/5 mL (500 mL) [contains polyethylene glycol (macrogol); grape flavor]
Generic: 5 mg/5 mL (5 mL, 500 mL); 10 mg/5 mL (500 mL)
Suspension Reconstituted ER, Oral:
Quillivant XR: 25 mg/5 mL (60 mL, 120 mL, 150 mL, 180 mL) [contains corn starch, sodium benzoate; banana flavor]
Tablet, Oral, as hydrochloride:
Ritalin: 5 mg
Ritalin: 10 mg, 20 mg [scored]
Generic: 5 mg, 10 mg, 20 mg
Tablet Chewable, Oral, as hydrochloride:
Generic: 2.5 mg, 5 mg, 10 mg
Tablet Chewable Extended Release, Oral, as hydrochloride:
QuilliChew ER: 20 mg, 30 mg [scored; contains aspartame]
QuilliChew ER: 40 mg [contains aspartame]
Tablet Extended Release, Oral, as hydrochloride:
Concerta: 18 mg, 27 mg, 36 mg, 54 mg
Relexxii: 18 mg
Relexxii: 27 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]
Relexxii: 36 mg
Relexxii: 45 mg [contains fd&c red #40(allura red ac)aluminum lake]
Relexxii: 54 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]
Relexxii: 63 mg
Relexxii: 72 mg [contains fd&c blue #1 (brill blue) aluminum lake]
Generic: 10 mg, 18 mg, 20 mg, 27 mg, 36 mg, 45 mg, 54 mg, 63 mg, 72 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride:
Generic: 18 mg, 27 mg, 36 mg, 54 mg
Tablet Extended Release Disintegrating, Oral:
Cotempla XR-ODT: 8.6 mg, 17.3 mg, 25.9 mg
May be product dependent
Capsule ER 24 Hour Therapy Pack (Aptensio XR Oral)
10 mg (per each): $10.00
15 mg (per each): $10.10
20 mg (per each): $10.00
30 mg (per each): $10.00
40 mg (per each): $10.00
50 mg (per each): $10.00
60 mg (per each): $10.00
Capsule ER 24 Hour Therapy Pack (Jornay PM Oral)
20 mg (per each): $18.24
40 mg (per each): $18.24
60 mg (per each): $18.24
80 mg (per each): $18.24
100 mg (per each): $18.24
Capsule ER 24 Hour Therapy Pack (Methylphenidate HCl ER (LA) Oral)
10 mg (per each): $10.27 - $12.33
20 mg (per each): $5.67 - $12.98
30 mg (per each): $5.80 - $13.27
40 mg (per each): $5.96 - $13.64
60 mg (per each): $12.37 - $14.84
Capsule ER 24 Hour Therapy Pack (Methylphenidate HCl ER (XR) Oral)
10 mg (per each): $7.17 - $9.50
15 mg (per each): $7.17 - $9.50
20 mg (per each): $7.17 - $9.50
30 mg (per each): $7.17 - $9.50
40 mg (per each): $7.17 - $9.50
50 mg (per each): $7.17 - $9.50
60 mg (per each): $7.17 - $9.50
Capsule ER 24 Hour Therapy Pack (Ritalin LA Oral)
10 mg (per each): $15.14
20 mg (per each): $15.14
30 mg (per each): $15.49
40 mg (per each): $15.92
Capsule Extended Release (Metadate CD Oral)
10 mg (per each): $23.96
20 mg (per each): $23.96
30 mg (per each): $23.96
40 mg (per each): $23.96
50 mg (per each): $23.96
60 mg (per each): $23.96
Capsule Extended Release (Methylphenidate HCl ER (CD) Oral)
10 mg (per each): $5.60 - $8.42
20 mg (per each): $5.60 - $8.42
30 mg (per each): $5.60 - $8.42
40 mg (per each): $7.12 - $11.55
50 mg (per each): $9.44 - $14.19
60 mg (per each): $9.44 - $14.19
Chewable (Methylphenidate HCl Oral)
2.5 mg (per each): $1.92 - $3.16
5 mg (per each): $2.23 - $4.51
10 mg (per each): $2.54 - $6.43
Patch (Daytrana Transdermal)
10 mg/9 hrs (per each): $7.22
15 mg/9 hrs (per each): $7.22
20 mg/9 hrs (per each): $7.22
30 mg/9 hrs (per each): $7.22
Patch (Methylphenidate Transdermal)
10 mg/9 hrs (per each): $16.76 - $17.64
15 mg/9 hrs (per each): $16.76 - $17.64
20 mg/9 hrs (per each): $16.76 - $17.64
30 mg/9 hrs (per each): $16.76 - $17.64
Solution (Methylin Oral)
5 mg/5 mL (per mL): $0.17
10 mg/5 mL (per mL): $0.24
Solution (Methylphenidate HCl Oral)
5 mg/5 mL (per mL): $0.25 - $0.90
10 mg/5 mL (per mL): $0.38 - $1.29
Suspension Reconstituted ER (Quillivant XR Oral)
25 mg/5 mL (per mL): $3.39
Tablet Chewable Extended Release (QuilliChew ER Oral)
20 mg (per each): $14.91
30 mg (per each): $14.91
40 mg (per each): $14.91
Tablet Extended Release Dispersible (Cotempla XR-ODT Oral)
8.6 mg (per each): $20.53
17.3 mg (per each): $20.53
25.9 mg (per each): $20.53
Tablet, 24-hour (Methylphenidate HCl ER Oral)
18 mg (per each): $6.22
27 mg (per each): $6.38
36 mg (per each): $6.58
54 mg (per each): $7.16
Tablet, controlled release (Concerta Oral)
18 mg (per each): $15.48
27 mg (per each): $15.87
36 mg (per each): $16.37
54 mg (per each): $17.81
Tablet, controlled release (Methylphenidate HCl ER (OSM) Oral)
18 mg (per each): $0.89 - $13.21
27 mg (per each): $0.89 - $13.54
36 mg (per each): $1.06 - $13.97
45 mg (per each): $22.90
54 mg (per each): $1.06 - $15.20
63 mg (per each): $24.19
72 mg (per each): $24.86
Tablet, controlled release (Methylphenidate HCl ER Oral)
10 mg (per each): $7.50 - $8.00
20 mg (per each): $7.75 - $8.25
Tablet, controlled release (Relexxii Oral)
18 mg (per each): $14.21
27 mg (per each): $14.57
36 mg (per each): $15.02
45 mg (per each): $25.44
54 mg (per each): $16.35
63 mg (per each): $26.87
72 mg (per each): $27.62
Tablets (Methylphenidate HCl Oral)
5 mg (per each): $0.61 - $0.74
10 mg (per each): $0.36 - $1.05
20 mg (per each): $0.34 - $1.51
Tablets (Ritalin Oral)
5 mg (per each): $1.00
10 mg (per each): $1.43
20 mg (per each): $2.05
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Extended Release, Oral:
Biphentin: 15 mg [contains d&c red #28, fd&c red #40 (allura red ac dye), quinoline (d&c yellow #10) aluminum lake]
Biphentin: 80 mg [contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
Generic: 15 mg, 80 mg
Capsule Extended Release, Oral, as hydrochloride:
Biphentin: 10 mg [contains fd&c blue #1 (brill blue) aluminum lake]
Biphentin: 20 mg [contains d&c red 33, quinoline (d&c yellow #10) aluminum lake]
Biphentin: 30 mg [contains fd&c blue #1 (brill blue) aluminum lake]
Biphentin: 40 mg [contains d&c red #28, fd&c blue #1 (brill blue) aluminum lake, fd&c red #40 (allura red ac dye)]
Biphentin: 50 mg [contains quinoline (d&c yellow #10) aluminum lake]
Biphentin: 60 mg
Generic: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg
Capsule Extended Release 24 Hour, Oral:
Foquest: 100 mg
Capsule Extended Release 24 Hour, Oral, as hydrochloride:
Foquest: 25 mg [contains fd&c blue #1 (brilliant blue)]
Foquest: 35 mg [contains fd&c yellow #6 (sunset yellow)]
Foquest: 45 mg [contains fd&c yellow #5 (tartrazine)]
Foquest: 55 mg [contains fd&c blue #1 (brilliant blue)]
Foquest: 70 mg, 85 mg
Tablet, Oral, as hydrochloride:
Ritalin: 10 mg [DSC]
Generic: 5 mg, 10 mg, 20 mg
Tablet Extended Release, Oral, as hydrochloride:
Concerta: 18 mg, 27 mg, 36 mg, 54 mg
Ritalin SR: 20 mg [DSC]
Generic: 18 mg, 20 mg, 27 mg, 36 mg, 54 mg
C-II
Oral:
Short-acting immediate release: Chewable tablets, Methylin (oral solution), and Ritalin (tablets): Administer each dose 30 to 45 minutes before a meal. Ensure last daily dose is administered before 6:00 PM if difficulty sleeping occurs. Administer chewable tablet with ≥8 ounces of water or other fluid.
Intermediate-acting extended release :
Methylphenidate ER tablets (AB rated generics to Metadate ER or Methylin ER): Administer 30 to 45 minutes before a meal. Swallow whole with water or other fluid; do not crush or chew tablet.
Ritalin SR [Canadian product]: Swallow whole; do not crush or chew tablet.
Long-acting extended release:
Adhansia XR: Administer in the morning with or without food. Swallow whole with full glass of water; do not crush or chew capsules. Alternatively, capsules may be opened and the contents sprinkled onto a tablespoon of applesauce or yogurt. Swallow mixture immediately or within 10 minutes without chewing; discard if not administered within 10 minutes of mixing. Do not crush, chew, or divide capsule contents.
Aptensio XR, Jornay PM, Metadate CD, Ritalin LA: Administer Aptensio XR, Metadate CD, and Ritalin LA in the morning and Jornay PM in the evening between 6:30 PM to 9:30 PM. Administer with or without food; capsules may be opened, and the contents sprinkled onto a small amount (equal to 1 tablespoon) of cold applesauce. Swallow applesauce mixture immediately without chewing. Do not crush, chew, or divide capsule contents.
Biphentin, Foquest [Canadian products]: Administer in the morning. Swallow whole with full glass of water; do not crush or chew capsules. Alternatively, capsules may be opened, and the contents sprinkled onto applesauce, ice cream, or yogurt, but the beads must not be crushed or chewed.
Biphentin should be administered immediately after or within 30 minutes of sprinkling capsule contents on food; after administration patients should rinse their mouths with water and swallow. Discard if not administered within 30 minutes of mixing.
Foquest should be administered immediately after or within 10 minutes of sprinkling capsule contents on food; after administration patients should rinse their mouths with water and swallow. Discard if not administered within 10 minutes of mixing.
Concerta, Relexxii: Administer in the morning. May be taken with or without food but must be taken with water or other fluid. Do not crush, chew, or divide tablet.
QuilliChew ER: Administer in the morning with or without food. Tablets are scored and may be halved.
Quillivant XR: Administer in the morning with or without food. Shake bottle ≥10 seconds prior to administration. Use the oral dosing dispenser provided; wash after each use.
Bariatric surgery:
Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER tablets should be swallowed whole. Do not cut, chew, or crush. IR tablet, chewable tablet, oral solution, and oral suspension formulations are available. ER chewable tablet, ER orally dissolvable tablet, and transdermal formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, close clinical monitoring is advised in the immediate postoperative phase for the theoretical circumstance of altered absorption after bariatric surgery.
Topical: Long-acting transdermal: Daytrana: Apply to clean, dry, non-oily, intact skin to the hip area, avoiding the waistline; do not premedicate the patch site with hydrocortisone or other solutions, creams, ointments, or emollients. Apply at the same time each day to alternating hips. Press firmly for 30 seconds to ensure proper adherence. Avoid exposure of application site to external heat source, which may increase the amount of drug absorbed. If difficulty is experienced when separating the patch from the liner or if any medication (sticky substance) remains on the liner after separation, discard that patch and apply a new patch. Do not use a patch that has been damaged or torn; do not cut patch. If patch should dislodge, may replace with new patch (to different site) but total wear time should not exceed 9 hours; do not reapply with dressings, tape, or common adhesives. Patch may be removed early if a shorter duration of effect is desired or if late day side effects occur. Wash hands with soap and water after handling. Avoid touching the sticky side of the patch. If patch removal is difficult, an oil-based product (eg, petroleum jelly, olive oil) may be applied to the patch edges to aid removal; never apply acetone-based products (eg, nail polish remover) to patch. Dispose of used patch by folding adhesive side onto itself, and discard in toilet or appropriate lidded container; do not flush the pouch or liner down the toilet.
Oral: To avoid insomnia, last daily dose of all products except Jornay PM should be administered several hours before retiring.
Immediate-release formulations:
Tablet (Ritalin), oral solution (Methylin): Administer ~30 to 45 minutes before meals. Ensure last daily dose is administered before 6 PM if difficulty sleeping occurs.
Chewable tablet (Methylin): Administer ~30 to 45 minutes before meals with at least 8 ounces of water or other fluid; choking may occur if not enough fluids are taken. Ensure last daily dose is administered before 6 PM if difficulty sleeping occurs.
Extended-/sustained-release formulations:
Tablets:
Concerta: May be administered without regard to food, but must be taken with liquids; administer dose once daily in the morning; do not crush, chew, or divide tablets.
Metadate ER: May be taken with or without food. Swallow whole; do not crush, chew, or break tablets.
Relexxii: May be administered without regard to food; swallow whole with liquid; do not crush, chew, or divide tablets.
Ritalin SR: Administer 30 to 45 minutes before a meal. Swallow whole; do not crush, chew, or break tablets.
Capsules:
Adhansia XR: Administer in the morning with or without food; swallow capsule whole; do not crush, chew, or divide capsule or its contents. Capsules may be opened and entire contents sprinkled onto a tablespoon of applesauce or yogurt; use within 10 minutes (immediately use is preferable); mixture must be consumed without chewing; do not store for future use. Missed doses should not be administered later in the day, and do not administer additional doses to make up for missed dose; resume normal dosing regimen the next morning.
Aptensio XR: Administer in the morning with or without food; swallow capsule whole; do not crush, chew, or divide capsule or its contents; capsules may be opened and the contents sprinkled onto applesauce; mixture must be consumed immediately without chewing; do not store for future use.
Biphentin [Canadian product]: Administer in the morning; do not crush or chew capsule or its contents; capsules may be opened and the contents sprinkled onto applesauce, ice cream, or yogurt; mixture must be consumed immediately without chewing; do not store for future use.
Foquest [Canadian product]: Administer in the morning with a full glass of water; do not crush or chew capsule or its contents; capsules may be opened and the contents sprinkled onto a tablespoon of applesauce, ice cream, or yogurt; mixture must be consumed within 10 minutes without chewing.
Jornay PM: Administer dose once daily in the evening between 6:30 and 9:30 PM; administer consistently either with or without food; swallow capsule whole; do not crush, chew, or divide capsule or its contents; capsules may be opened and the contents sprinkled onto applesauce; mixture must be consumed immediately without chewing; do not store for future use. Missed doses should be taken as soon as remembered if the same evening; if missed dose remembered the following morning, it should be skipped.
Methylphenidate extended-release capsules (eg, generic Metadate CD): Administer dose once daily in the morning, before breakfast, with liquids; capsule may be swallowed whole; do not crush, chew, or divide capsule or its contents; capsules may be opened and contents sprinkled on a small amount (one tablespoonful) of applesauce; immediately consume drug/applesauce mixture; do not store for future use; swallow applesauce without chewing; drink fluids after consuming drug/applesauce mixture to ensure complete swallowing of beads.
Ritalin LA: Administer dose once daily in the morning; may be administered with or without food (but some food consumed at breakfast may delay absorption); capsule may be swallowed whole; do not crush, chew, or divide capsule or its contents; may be opened and contents sprinkled on a small amount (one spoonful) of applesauce. Note: Applesauce should not be warm; immediately consume drug/applesauce mixture; do not store for future use.
Orally disintegrating tablet (Cotempla XR-ODT): Administer in the morning consistently with or without food. Remove the tablet from blister pack with dry hands by peeling back (do not push tablet through foil), and administer immediately. Allow the tablet to dissolve on the tongue without chewing or crushing; no liquid is needed.
Powder for oral suspension (Quillivant XR): Administer in the morning with or without food. Shake bottle ≥10 seconds prior to administration. Use the oral dosing dispenser provided; wash after each use.
Topical: Transdermal (Daytrana): Apply patch immediately after opening pouch and removing protective liner; do not use patch if pouch seal is broken; do not cut patch; do not use patches that are cut or damaged. If difficulty is experienced when separating the patch from the liner or if any medication (sticky substance) remains on the liner after separation, discard that patch and apply a new patch. Apply to clean, dry, healthy skin on the hip; do not apply to oily, damaged, inflamed, or irritated skin; do not apply to the waistline; do not premedicate the patch site with hydrocortisone or other solutions, creams, ointments, or emollients. Apply at the same time each day, 2 hours before effect is needed. Alternate site of application daily (ie, use alternate hip). Press patch firmly for 30 seconds to ensure proper adherence, especially around the edges. Remove patch typically 9 hours after application. Patch may be removed earlier if a shorter duration of action is required or if late day adverse effects occur or may be worn for up to 16 hours if extended duration of effects are needed (Ref).
Avoid exposure of application site to external heat source (eg, hair dryers, electric blankets, heating pads, heated water beds), which may significantly increase the rate and amount of drug absorbed. Exposure of patch to water during swimming, bathing, or showering may affect patch adherence. Do not reapply patch with dressings, tape, or other adhesives. If patch should become dislodged, may replace with new patch (to different site) but total wear time for the day should not exceed 9 hours, even if more than one patch is used.
During removal, peel off patch slowly. If needed, patch removal may be helped by applying an oil-based product (ie, mineral oil, olive oil, or petroleum jelly) to the patch edges, gently working it underneath the patch edges. If a patch is not able to be removed, contact a physician or pharmacist. Nonmedical adhesive removers and acetone-based products, such as nail polish remover, should not be used to remove patches or adhesive. If adhesive residue remains on the skin after patch removal, use an oil-based product and gently rub area to remove adhesive. Avoid touching the sticky side of the patch. Wash hands with soap and water after handling.
Dispose of used patch by folding adhesive side onto itself, and flush down the toilet or discard in appropriate lidded container; discard unused patches that are no longer needed in the same manner; protective pouch and liner should be discarded in an appropriate lidded container. Note: Used patches contain residual drug; keep all transdermal patches out of the reach of children.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Adhansia XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212038s002lbl.pdf#page=25
Aptensio XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/205831s008lbl.pdf#page=19
Concerta: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021121s049lbl.pdf#page=30
Cotempla XR-ODT: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/205489s012lbl.pdf#page=24
Daytrana: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021514s032lbl.pdf#page=25
Jornay PM: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209311s010lbl.pdf#page=20
Metadate CD: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021259s034lbl.pdf#page=16
Methylin chewable tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021475s012lbl.pdf#page=13
Methylin oral solution: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021419s023lbl.pdf#page=17
QuilliChew ER: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/207960s012lbl.pdf#page=21
Quillivant XR extended release oral suspension: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202100s018lbl.pdf#page=21
Relexxii: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216117s001lbl.pdf#page=25
Ritalin: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/010187s092s096lbl.pdf#page18
Ritalin LA: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021284s042s046lbl.pdf#page18
Attention-deficit/hyperactivity disorder: Treatment of attention-deficit/hyperactivity disorder (ADHD) in patients ≥6 years of age.
Narcolepsy (Methylin, methylphenidate ER tablets [AB rated generics to Metadate ER or Methylin ER], Ritalin, and Ritalin SR [Canadian product] only): Symptomatic management of narcolepsy.
Fatigue, severe, cancer related or in palliative care setting; Major depressive disorder (unipolar) in medically ill, palliative care, terminal illness, or elderly patients
Metadate CD may be confused with Metadate ER
Metadate ER may be confused with methadone
Methylphenidate may be confused with methadone
QuilliChew ER may be confused with Quillivant XR
Ritalin may be confused with Rifadin
Ritalin LA may be confused with Ritalin SR
Ritalin [US, Canada, and multiple international markets] may be confused with ritodrine [multiple international markets]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Risk X: Avoid combination
Alcohol (Ethyl): May enhance the adverse/toxic effect of Methylphenidate. Alcohol (Ethyl) may increase the serum concentration of Methylphenidate. Risk X: Avoid combination
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Antihypertensive Agents: Methylphenidate may diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents: May enhance the adverse/toxic effect of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor therapy
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Asenapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Benperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Blonanserin: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Bromperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy
Cannabidiol: May increase the serum concentration of Methylphenidate. Risk C: Monitor therapy
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cariprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Clothiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CloZAPine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy
DroPERidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Esketamine: May enhance the hypertensive effect of CNS Stimulants. Risk C: Monitor therapy
Flupentixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Haloperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Iloperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Inhalational Anesthetics: Dexmethylphenidate-Methylphenidate may enhance the hypertensive effect of Inhalational Anesthetics. Risk X: Avoid combination
Iobenguane Radiopharmaceutical Products: CNS Stimulants may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination
Ioflupane I 123: Methylphenidate may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination
Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy
Loxapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lumateperone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lurasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Molindone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of Methylphenidate. Risk X: Avoid combination
OLANZapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Paliperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Periciazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Perphenazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
PHENobarbital: Methylphenidate may increase the serum concentration of PHENobarbital. Risk C: Monitor therapy
Pimozide: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor therapy
Primidone: Methylphenidate may increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations could become elevated. Methylphenidate may increase the serum concentration of Primidone. Risk C: Monitor therapy
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Promazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
QUEtiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Quinolones: Methylphenidate may enhance the cardiotoxic effect of Quinolones. Risk C: Monitor therapy
RisperiDONE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Serotonergic Agents (High Risk): Dexmethylphenidate-Methylphenidate may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Sertindole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Solriamfetol: CNS Stimulants may enhance the hypertensive effect of Solriamfetol. CNS Stimulants may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Sulpiride: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Thioridazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Thiothixene: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Ziprasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Ethanol: Alcohol consumption increases the rate of methylphenidate release from ER capsules (eg, Adhansia XR, Jornay PM, Metadate CD, Ritalin LA) and QuilliChew ER (ER chewable tablet), but not from Concerta (ER tablet) or Relexxii (ER tablet); in vitro studies showed that an alcohol concentration of 40% resulted in 84%, and 98% of the methylphenidate being released in the first hour with Metadate CD and Ritalin LA, respectively, and 97% of the methylphenidate being released in 2 hours with Jornay PM; a study involving Adhansia XR showed that an alcohol concentration of 40% resulted in 71% of a 70 mg dose and 61% of a 100 mg dose being released in the first 2 hours; a study involving QuilliChew ER showed that an alcohol concentration of 40% resulted in 90% of the methylphenidate being released in the first half hour. Management: Avoid consuming alcohol during therapy.
Food: Food may increase oral absorption of IR tablet/solution/chewable tablet and methylphenidate ER tablets (AB rated generics to Metadate ER or Methylin ER). Management: Administer 30 to 45 minutes before meals.
Information related to the use of methylphenidate in pregnant women with attention-deficit/hyperactivity disorder (Ornoy 2018) or narcolepsy (Calvo-Ferrandiz 2018; Maurovich-Horvat 2013; Thorpy 2013) is limited and outcome data is conflicting (Ornoy 2018). If treatment of ADHD in pregnancy is needed, methylphenidate may be considered (Larsen 2015; McAllister-Williams 2017).
Data collection to monitor pregnancy and infant outcomes following exposure to methylphenidate is ongoing. Health care providers are encouraged to enroll females exposed to methylphenidate during pregnancy in the National Pregnancy Registry for Psychostimulants at 1-866-961-2388.
Methylphenidate is present in breast milk.
The relative infant dose (RID) of methylphenidate is 0.7% when calculated using the highest breast milk concentration located and compared to a weight-adjusted maternal dose of 52 mg/day.
In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).
The RID of methylphenidate was calculated using a milk concentration of 19 mcg/L, providing an absolute daily infant dose via breast milk of 2.9 mcg/kg/day. This milk concentration was obtained following maternal administration methylphenidate to three women for ADHD. Maternal doses ranged from 35 to 80 mg/day (Hackett 2006). Authors of two additional case reports calculated the RID of methylphenidate <1% (Hackett 2006; Spigset 2007). In a case report, methylphenidate was no longer detectable in breast milk 20 to 21 hours after the maternal dose following administration of the immediate release tablet (Spigset 2007).
Adverse events were not noted in three case reports (Bolea-Alamanac 2014a; Hackett 2006; Spigset 2007); however, infants in two cases were older (6 months of age and 11 months of age) and exposure was limited (Hackett 2006; Spigset 2007). Long-term developmental effects have not been studied. Growth and medical development were normal in one child up to 1 year of age (Bolea-Alamanac 2014a).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Monitor breastfeeding infants for adverse reactions, such as agitation, anorexia, insomnia, and reduced weight gain.
Administer the short-acting IR tablet (Ritalin), IR solution (Methylin), and IR chewable tablet 30 to 45 minutes before meals. Some products may contain phenylalanine.
CBC with differential and platelet count periodically with prolonged therapy. Cardiac evaluation (including medical or family history of sudden death or ventricular arrhythmia; ECG as indicated) should be completed at baseline and on any patient who develops exertional chest pain, unexplained syncope, and any symptom of cardiac disease during treatment with stimulants. Monitor blood pressure and heart rate (baseline, following dose increases and periodically during treatment); growth rate (height and weight) and appetite in children; weight in adults; signs of peripheral vasculopathy (eg, digital changes); sleep and behavioral changes; assess family history and evaluate for tics or Tourette syndrome prior to initiation of therapy; assess for new signs or worsening of tics or Tourette syndrome during treatment; intraocular pressure (IOP) in patients with history of open angle glaucoma or increased IOP. Assess for risk of abuse prior to prescribing and signs of misuse, abuse, or substance use disorder throughout treatment (NICE 2018). Screen for bipolar disorder and risk factors for developing a manic episode prior to treatment; monitor for psychotic or manic symptoms (eg, delusional thinking, hallucinations, mania) or suicide-related behavior; in children monitor for development or worsening of aggressive behavior or hostility.
Transdermal: Signs of worsening erythema, blistering or edema which does not improve within 48 hours of patch removal, or spreads beyond patch site.
Mild CNS stimulant; blocks the reuptake of norepinephrine and dopamine into presynaptic neurons; appears to stimulate the cerebral cortex and subcortical structures similar to amphetamines
Onset of action (AAP [Wolraich 2011]):
Children:
Oral:
ER formulations (capsule [Metadate CD, Ritalin LA], tablets [Concerta]): 20 to 60 minutes
IR formulations (chewable tablet, oral solution, tablet [Methylin, Ritalin]): 20 to 60 minutes
Sustained-release tablet (Ritalin SR [Canadian product]): 60 to 180 minutes
Transdermal (Daytrana): 60 minutes
Adults: Oral: Controlled-release: Foquest [Canadian product]: Within 1 hour
Maximum effect: Oral: IR tablet: Within 2 hours; Sustained-release tablet (Ritalin SR [Canadian product]): Within 4 to 7 hours
Duration of action:
Oral:
Controlled-release capsule (Foquest [Canadian product]): 16 hours
ER capsule: Metadate CD, Ritalin LA: 6 to 8 hours (AAP [Wolraich 2011]); Aptensio XR: ≤16 hours
ER tablet (Concerta): 8 to 12 hours (AAP [Wolraich 2011]; Jain 2017)
ER tablet (AB rated generics to Metadate ER or Methylin ER): ~8 hours.
IR formulations (chewable tablet, oral solution, IR tablet [Methylin, Ritalin]): 3 to 5 hours (AAP [Wolraich 2011]; Jain 2017)
Sustained-release tablet (Ritalin SR [Canadian product]): 2 to 8 hours (AAP [Wolraich 2011]; Jain 2017)
Transdermal (Daytrana): 11 to 12 hours (AAP [Wolraich 2011])
Absorption:
Oral: Readily absorbed
Controlled-release capsule:
Biphentin [Canadian product]: Food delayed initial peak slightly (~18 minutes); relative to immediate-release tablets, AUC is similar in fed or fasted state (~100%)
Foquest [Canadian product]: Food does not significantly affect AUC and Cmax
ER capsule:
Adhansia XR: A high fat meal increased the time to first and second Cmax by about 1 hour. When administered with a 40% alcohol concentration in fasted healthy adults, there was a 1.4-fold increase in the peak plasma methylphenidate concentration and a 1.3-fold increase in the extent of absorption; in vitro studies at an alcohol concentration of 40% also demonstrated faster release with 71% of a 70 mg dose and 61% of a 100 mg dose of methylphenidate released at hour 2.
Aptensio XR: A high-fat meal increased Cmax (~28%) and AUC (~19%). At an alcohol concentration up to 40% there was 96% release of methylphenidate within 2 hours.
Jornay PM: Initial absorption is delayed with ≤5% of total drug available within first 10 hours after dosing. A high-fat meal at night decreased Cmax (14%) and extended the median Tmax by ~2.5 hours; a high-fat morning meal had no effect on the pharmacokinetics. At an alcohol concentration of 40%, there was an increase in the release rate of methylphenidate, resulting in 97% of the methylphenidate being released in 2 hours.
Metadate CD: A high-fat meal delayed the early peak (~1 hour), and increased Cmax (~30%) and AUC (~17%). At an alcohol concentration of 40%, there was an increase in the release rate of methylphenidate in the first hour, resulting in 84% of the methylphenidate being released.
Ritalin LA: A high-fat meal delayed absorption and peak times, but not the amount absorbed nor initial peak concentration (second peak lowered by ~25%). At an alcohol concentration of 40%, there was a 98% release of methylphenidate in the first hour.
ER chewable tablet: A high-fat meal increased Cmax (~20%) and AUCinf (~4%). At an alcohol concentration of 40%, there was an increase in the release rate of methylphenidate in the first half hour, resulting in 90% of the methylphenidate being released.
ER orally disintegrating tablet: Cotempla XR-ODT: A high-fat meal decreased Cmax (24%) and increased AUCinf (16%) and led to an earlier peak (~0.5 hour).
ER suspension: Quillivant XR: A high-fat meal led to an earlier peak (~1 hour), and increased Cmax (~28%) and AUC (~19%).
ER tablet (AB rated generics to Metadate ER or Methylin ER): A high-fat meal resulted in a faster peak (2.5 hours with meal compared to 3 hours fasting) and increased Cmax (27%) and AUC (25%).
IR chewable tablet: A high-fat meal delayed peak time (~1 hour) and increased AUC (~20%).
IR solution: Methylin: A high-fat meal delayed peak time (~1 hour), and increased Cmax (~13%) and AUC (~25%).
IR tablet: A high-fat meal, increased the AUC (25%) and Cmax (27%).
Transdermal: Absorption increased when applied to inflamed skin or exposed to heat. Absorption is continuous for 9 hours after application.
Distribution: Vd: d-methylphenidate: 2.65 ± 1.11 L/kg, l-methylphenidate: 1.80 ± 0.91 L/kg
Protein binding: 10% to 33%
Metabolism: Extensive metabolism, predominately via de-esterification by carboxylesterase CES1A1 to alpha-phenyl-piperidine acetic acid (PPAA; ritalinic acid) which has little to no pharmacologic activity.
Bioavailability:
ER capsule:
Aptensio XR: 102% (relative to IR oral product)
Jornay PM: 73.9% (relative to IR oral product)
ER suspension: Quillivant XR: 95% (relative to IR oral solution)
IR chewable tablets and oral solution: Bioequivalent to IR tablets
Sustained-release tablet (Ritalin SR [Canadian product]): 105% (49% to 168%) in children and 101% (85% to 152%) in adults (relative to IR oral product)
Transdermal patch (Daytrana): Lower first-pass effect compared to oral administration; thus, much lower doses (on a mg/kg basis) given via the transdermal route may still produce higher AUCs, compared to the oral route
Half-life elimination:
Controlled-release capsule: Biphentin [Canadian product]: Children: 2.4 hours; Adults: 2.1 hours; Foquest [Canadian product]: Adults: 6.95 ± 3.25 hours
ER capsule:
Adhansia XR:
Children 6 to 12 years of age: ~4 to 7 hours
Adolescents ≤17 years of age: ~5 hours
Adults: 7 hours
Aptensio XR: Adults: ~5 hours
Jornay PM: Adults: ~5.9 hours
Metadate CD: Adults: 6.8 hours.
Ritalin LA: Children: 1.5 to 4 hours; Adults: 3 to 4.2 hours
ER chewable tablets: ~5.2 hours
ER orally disintegrating tablet: 4 to 4.5 hours
ER suspension: Quillivant XR: Children ≥9 years of age, Adolescents, and Adults: ~5 hours
ER tablet: Concerta, Relexxii: Adolescents and Adults: ~3.5 hours
IR chewable tablet: Adults: 3 hours
IR solution: Methylin: Adults: 2.7 hours
IR tablet:
Children: 3.5 hours (1.5 to 5 hours)
Adults: 3.5 hours (1.3 to 7.7 hours)
Transdermal: Children and Adolescents 6 to 17 years of age: d-methylphenidate ~4 to 5 hours, l-methylphenidate 1.4 to 2.9 hours
Time to peak:
Controlled-release capsule:
Biphentin [Canadian product]: Children: Initial: ~2.5 hours; Adults: Initial: ~2 hours
Foquest [Canadian product]: Children: Initial peak between 1.5 to 2.0 hours followed by a second peak between 9 to 11 hours; Adults: Initial peak at ~1.6 hours followed by second peak at ~12.5 hours (range: 11 to 16 hours)
ER capsule:
Adhansia XR:
Children 6 to 12 years of age: Initial: 2 hours (range: 1 to 4 hours); Second peak: 10 hours (8 to 14 hours)
Adolescents ≤17 years of age: Initial: 2 hours (range: 1 to 4 hours); Second peak: 11 hours (8 to 14 hours)
Adults: Initial: 1.5 hours (range: 1 to 2.5 hours); Second peak: ~12 hours (range: 8.5 to 16 hours)
Aptensio XR: Adults: Initial: ~2 hours; Second peak: ~8 hours
Jornay PM: Adults: 14 hours
Metadate CD: Children: Initial: ~1.5 hours; Second peak: ~4.5 hours.
Ritalin LA:
Children: Initial: 1 to 3 hours; Second peak: 5 to 11 hour
Adults: Initial: 1.3 to 4 hours; Second peak: 4.3 to 6.5 hours
ER chewable tablet: QuilliChew ER: Adults: 5 hours (median)
ER orally disintegrating tablet: Cotempla XR-ODT: ~5 hours
ER suspension: Quillivant XR: Children (9 to 12 years of age): 4.05 hours (range: 3.98 to 6 hours); Adolescents (13 to 15 years of age): 2 hours (range: 1.98 to 4 hours); Adults: 4 hours (range: 1.3 to 7.3 hours)
ER tablet:
AB rated generics to Metadate ER or Methylin ER: Children: 4.7 hours (1.3 to 8.2 hours).
Concerta: Initial: ~1 hours, followed by gradually ascending concentrations over 5 to 9 hours; Mean peak: 6 to 10 hours.
Relexxii: Initial: ~1.5 hours, followed by a second peak around 5.5 hours.
IR chewable tablet: ~1 to 2 hours
IR solution: Methylin: 1 to 2 hours
IR tablet: Children: 1.9 hours (range: 0.3 to 4.4 hours); time to peak is faster after a high-fat meal as compared to without food (median Tmax: 2.5 hours versus 3 hours, respectively).
Sustained-release tablet (Ritalin SR [Canadian product]): Children: 4.7 hours (range: 1.3 to 8.2 hours)
Transdermal: ~8 to 10 hours
Excretion: Urine (78% to 97% as metabolites and unchanged drug); Feces (1% to 3%)
Pediatric:
ER capsule: Ritalin LA: Time until the between peak minimum and the time until the second peak were delayed and more variable in children 10 to 12 years of age compared to adults. After a 20 mg dose, concentrations in children were approximately twice the concentrations observed in adults 18 to 35 years of age.
ER suspension: Quillivant XR: After a single oral dose of 60 mg plasma concentrations of methylphenidate in children (9 to 12 years of age) were approximately twice the concentrations observed in adults.
Transdermal: The Cmax and AUC of d-methylphenidate were ~50% lower in adolescents, compared to children, following either a 1-day or 7-day administration of 10 mg/9 hours.
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