Skip to Content

Methylphenidate

Medically reviewed by Drugs.com. Last updated on May 28, 2019.

Pronunciation

(meth il FEN i date)

Index Terms

  • Adhansia XR
  • Methylphenidate HCl
  • Methylphenidate Hydrochloride
  • NWP09

Dosage Forms

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 [DSC], 20 mg [DSC], 30 mg [DSC] [contains fd&c blue #2 (indigotine)]

Metadate CD: 40 mg [DSC]

Metadate CD: 50 mg [DSC] [contains fd&c blue #2 (indigotine)]

Metadate CD: 60 mg [DSC]

Generic: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg

Capsule Extended Release 24 Hour, Oral, as hydrochloride:

Adhansia XR: 45 mg [contains tartrazine (fd&c yellow #5)]

Aptensio XR: 10 mg [contains brilliant blue fcf (fd&c blue #1)]

Aptensio XR: 15 mg [contains fd&c red #40, fd&c yellow #10 (quinoline yellow)]

Aptensio XR: 20 mg [contains fd&c yellow #10 (quinoline yellow)]

Aptensio XR: 30 mg [contains brilliant blue fcf (fd&c blue #1)]

Aptensio XR: 40 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]

Aptensio XR: 50 mg [contains fd&c yellow #10 (quinoline yellow)]

Aptensio XR: 60 mg

Jornay PM: 20 mg, 40 mg, 60 mg, 80 mg, 100 mg [contains brilliant blue fcf (fd&c blue #1)]

Ritalin LA: 10 mg, 20 mg, 30 mg, 40 mg, 60 mg [DSC]

Generic: 10 mg, 20 mg, 30 mg, 40 mg, 60 mg

Patch, Transdermal:

Daytrana: 10 mg/9 hr (1 ea, 30 ea); 15 mg/9 hr (30 ea); 20 mg/9 hr (1 ea, 30 ea); 30 mg/9 hr (30 ea)

Solution, Oral, as hydrochloride:

Methylin: 5 mg/5 mL (500 mL); 10 mg/5 mL (500 mL) [contains polyethylene glycol; grape flavor]

Generic: 5 mg/5 mL (500 mL); 10 mg/5 mL (500 mL)

Suspension Reconstituted, Oral, as hydrochloride:

Quillivant XR: 25 mg/5 mL (60 mL, 120 mL, 150 mL, 180 mL) [contains corn starch, sodium benzoate; banana flavor]

Quillivant XR: 25 mg/5 mL (60 mL [DSC], 120 mL [DSC], 150 mL [DSC], 180 mL [DSC]) [contains 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:

Methylin: 2.5 mg [DSC], 5 mg [DSC] [contains aspartame; grape flavor]

Methylin: 10 mg [DSC] [scored; contains aspartame; grape flavor]

Generic: 2.5 mg, 5 mg, 10 mg

Tablet Chewable Extended Release, Oral, as hydrochloride:

QuilliChew ER: 20 mg [DSC] [contains aspartame]

QuilliChew ER: 20 mg [scored; contains aspartame]

QuilliChew ER: 30 mg [DSC] [contains aspartame]

QuilliChew ER: 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

Metadate ER: 20 mg [additive free, color free]

Relexxii: 72 mg [contains fd&c blue #1 aluminum lake]

Generic: 10 mg, 18 mg, 20 mg, 27 mg, 36 mg, 54 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

Brand Names: U.S.

  • Adhansia XR
  • Aptensio XR
  • Concerta
  • Cotempla XR-ODT
  • Daytrana
  • Jornay PM
  • Metadate CD [DSC]
  • Metadate ER
  • Methylin
  • QuilliChew ER
  • Quillivant XR
  • Relexxii
  • Ritalin
  • Ritalin LA

Pharmacologic Category

  • Central Nervous System Stimulant

Pharmacology

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

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: Metadate ER: Food resulted in greater Cmax and AUC compared to fasting.

IR chewable tablet: Methylin: 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

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.

Excretion

Urine (78% to 97% as metabolites and unchanged drug); Feces (1% to 3%)

Onset of Action

Children (AAP 2011):

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): 60 to 180 minutes

Transdermal (Daytrana): 60 minutes

Adults: Oral: Controlled-release capsule: Foquest [Canadian product]: Within 1 hour

Maximum effect: Oral: IR tablet: Within 2 hours; Sustained-release tablet: Within 4 to 7 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 hours

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: Concerta: Initial: ~1 hours, followed by gradually ascending concentrations over 5 to 9 hours; Mean peak: 6 to 10 hours

IR chewable tablet: Methylin: ~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: Children: 4.7 hours (range: 1.3 to 8.2 hours)

Transdermal: ~8 to 10 hours

Duration of Action

Oral:

Controlled-release capsule (Foquest [Canadian product]): 16 hours

ER capsule: Metadate CD, Ritalin LA: 6 to 8 hours (AAP 2011); Aptensio XR: ≤16 hours

ER tablet (Concerta): 8 to 12 hours (AAP 2011; Jain 2017)

ER tablet (Metadate ER): 8 hours

IR formulations (chewable tablet, oral solution, IR tablet [Methylin, Ritalin]): 3 to 5 hours (AAP 2011; Jain 2017)

Sustained-release tablet (Ritalin-SR): 2 to 8 hours (AAP 2011; Jain 2017)

Transdermal (Daytrana): 11 to 12 hours (AAP 2011)

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: Adolescents and Adults: ~3.5 hours

IR chewable tablet: Methylin: 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

Protein Binding

10% to 33%

Special Populations: Children

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 18 to 35 year old adults.

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.

Use: Labeled Indications

Attention-deficit/hyperactivity disorder: Treatment of attention-deficit/hyperactivity disorder (ADHD)

Narcolepsy (Methylin, Metadate ER, Ritalin, and Ritalin SR): Symptomatic management of narcolepsy

Off Label Uses

Depression (terminal illness, palliative care, medically ill)

Data from a randomized, placebo-controlled study of hospice patients [Kerr 2012], a double-blind, randomized, placebo-controlled crossover trial in older adult patients who were medically ill [Wallace 1995], and a phase II open-label study in patients with advanced cancer [Homsi 2001] support the use of methylphenidate in the treatment of depression in medically ill older adult patients with terminal illness and/or receiving palliative care. Clinical experience as a systematic review also suggests the utility of methylphenidate in the treatment of this condition [Hardy 2009].

Fatigue, cancer related

Data from a randomized, placebo-controlled study of hospice patients support the use methylphenidate in the management of cancer-related fatigue in adults with advanced disease [Kerr 2012].

Based on the American Society of Clinical Oncology (ASCO) guidelines for screening, assessment, and management of fatigue in adult survivors of cancer, methylphenidate may be used to manage severe cancer-related fatigue in adult patients with advanced disease or in patients receiving active cancer treatment.

Major depressive disorder (antidepressant augmentation; geriatric patients)

Data from a limited number of patients studied suggest that methylphenidate augmentation of antidepressants may be beneficial for the treatment of major depressive disorder in geriatric patients and that it may accelerate treatment response [ Lavretsky 2006], [Lavretsky 2015].

Contraindications

US labeling: Hypersensitivity (eg, angioedema, anaphylaxis) to methylphenidate or any component of the formulation; use during or within 14 days following MAOI therapy

Additional contraindications:

Concerta, Daytrana, Metadate CD, Methylin, Metadate ER: Marked anxiety, tension, and agitation; glaucoma; family history or diagnosis of Tourette syndrome or tics

Metadate CD: Severe hypertension, heart failure, arrhythmia, hyperthyroidism or thyrotoxicosis, recent MI or angina; concomitant use of halogenated anesthetics; 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 MAO inhibitor therapy; family history or diagnosis of Tourette syndrome or tics (excluding Concerta), thyrotoxicosis, advanced arteriosclerosis, symptomatic cardiovascular disease, or moderate to severe hypertension

Additional contraindications:

Foquest: Known hypersensitivity or idiosyncrasy to sympathomimetic amines; history of drug abuse

Ritalin and Ritalin SR: Pheochromocytoma

Dosing: Adult

Attention-deficit/hyperactivity disorder: Oral:

IR products (tablets, chewable tablets, and solution): Initial: 5 mg twice daily, before breakfast and lunch; increase by 5 to 10 mg daily at weekly intervals; maximum dose: 60 mg/day (in 2 to 3 divided doses).

ER, sustained-release products (capsules, tablets, chewable tablets, orally disintegrating tablets, and oral suspension):

Adhansia XR: Initial: 25 mg once daily; may increase dose in 10 to 15 mg increments at intervals ≥5 days up to a maximum dose of 100 mg/day.

Conversion from IR methylphenidate formulations to Adhansia XR: Discontinue previous formulation and titrate using above schedule; do not substitute on a milligram-per-milligram basis.

Aptensio XR: Initial: 10 mg once daily; may increase dose in 10 mg increments at weekly intervals; maximum: 60 mg/day.

Biphentin [Canadian product]: Patients not currently taking methylphenidate: Initial: 10 to 20 mg once daily; may increase dose in 10 mg increments at weekly intervals to a maximum dose of 80 mg/day.

Conversion from IR methylphenidate formulations to Biphentin: Use equivalent total daily dose administered once daily.

Concerta (Adults <65 years of age):

Patients not currently taking methylphenidate: Initial: 18 to 36 mg once every morning

Patients currently taking IR methylphenidate or sustained release [Canadian product]: Initial: Note: Dosing based on current regimen and clinical judgment; suggested dosing listed below:

IR methylphenidate:

- Patients taking IR methylphenidate 5 mg 2 to 3 times daily: 18 mg once every morning

- Patients taking IR methylphenidate 10 mg 2 to 3 times daily: 36 mg once every morning

- Patients taking IR methylphenidate 15 mg 2 to 3 times daily: 54 mg once every morning

- Patients taking IR methylphenidate 20 mg 2 to 3 times daily: 72 mg once every morning

Sustained-release methylphenidate (Concerta Canadian product labeling):

- Patients taking methylphenidate sustained release 20 mg daily: 18 mg once every morning

- Patients taking methylphenidate sustained release 40 mg daily: 36 mg once every morning

- Patients taking methylphenidate sustained release 60 mg daily: 54 mg once every morning

Dose adjustment: May increase dose in increments of 18 mg at weekly intervals. A dosage strength of 27 mg is available for situations in which a dosage between 18 to 36 mg is desired. Maximum dose: 72 mg/day.

Foquest [Canadian product]:

Patients not currently taking methylphenidate: Initial: 25 mg once daily; may increase dose at 5-day intervals as needed to the lowest effective dose (maximum: 100 mg/day).

Patients currently taking methylphenidate: Initiate Foquest with the next lower strength based on total methylphenidate daily dose; may increase dose at 5-day intervals as needed to the lowest effective dose (maximum: 100 mg/day). Note: Do not substitute IR formulations or other controlled-release formulations with Foquest on a milligram-for-milligram basis (pharmacokinetic profiles differ).

Jornay PM: Initial: 20 mg once daily in the evening between 6:30 PM and 9:30 PM (eg, 8:00 PM); may increase dose in increments of 20 mg/day at weekly intervals; maximum daily dose: 100 mg/day.

Conversion from IR methylphenidate formulations to Jornay PM: Discontinue previous formulation and titrate using above schedule; do not substitute on a milligram-per-milligram basis.

Metadate ER, Ritalin-SR: Administer 2 or 3 times daily; replace IR tablets when the divided dosage corresponds to sustained-/extended-release tablet strength (duration of action: ~8 hours); maximum: 60 mg/day

Metadate CD, Quillivant XR: Initial: 20 mg once daily; may increase dose in 10 to 20 mg increments at weekly intervals; maximum: 60 mg/day

Conversion from other methylphenidate formulations to Quillivant XR: Discontinue previous formulation and titrate using above schedule; do not substitute on a milligram-per-milligram basis

QuilliChew ER: Initial: 20 mg once daily in the morning; may increase dose by 10, 15, or 20 mg at weekly intervals (tablets are scored and may be broken in half to achieve the 10 mg and 15 mg doses); maximum: 60 mg/day

Conversion from other methylphenidate formulations to QuilliChew ER: Discontinue previous formulation and titrate using above schedule; do not substitute on a milligram-per-milligram basis

Ritalin LA: Initial: 20 mg once daily (10 mg once daily may be considered for some patients); may increase dose in 10 mg increments at weekly intervals; maximum: 60 mg/day

Conversion from IR or sustained-release methylphenidate formulation to Ritalin LA: Use equivalent total daily dose administered once daily.

Narcolepsy: Oral:

IR tablets and solution (Methylin, Ritalin): Initial: 5 mg twice daily before breakfast and lunch; increase by 5 to 10 mg daily at weekly intervals; maximum dose: 60 mg/day (in 2 to 3 divided doses).

ER and sustained-release tablets (Metadate ER, Ritalin-SR): Administer 2 or 3 times daily. Replace IR tablets when the divided dosage corresponds to sustained-/extended-release tablet strength (duration of action: ~8 hours); maximum: 60 mg/day

Depression (terminal illness, palliative care, medically ill) (off-label use): Oral: Initial: Immediate release: 2.5 to 5 mg once daily before breakfast or twice daily before breakfast and lunch; increase by 2.5 to 5 mg daily every 1 to 3 days in divided doses before breakfast and lunch as tolerated; maximum dose: 20 to 40 mg/day (Hardy 2009; Kerr 2012). Do not use sustained release product.

Fatigue, cancer-related (off-label use): Oral: Immediate release: Initial: 5 mg twice daily (at 8 AM and 1 PM); increase based on tolerability in increments of 10 mg/day every 3 days up to a maximum of 40 mg/day (Kerr 2012).

Dosing: Geriatric

ADHD/Narcolepsy: Refer to adult dosing.

Major depressive disorder (antidepressant augmentation; off-label use): Oral: Initial: Immediate release: 2.5 mg twice daily (given at 9 am and 3 pm); increase dosage based on response and tolerability in increments of 2.5 mg twice daily every 3 to 4 days up to 40 mg/day. Average dose in clinical trials was ~15 to 16 mg/day (Lavrestky 2015; Lavrestky 2006).

Dosing: Pediatric

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 (AACAP [Pliszka 2007]; AAP 2011; Cortese 2018; NICE 2018). 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 (AAP 2011; Cortese 2018; NICE 2018).

Oral:

Immediate-release products (eg, Methylin, Ritalin):

Children 3 to 5 years, moderate to severe dysfunction: Limited data available; AAP considers first-line agent in this patient population if pharmacological treatment deemed necessary (AAP 2011); the American Academy of Child and Adolescent Psychiatry Preschool Psychopharmacology Working Group recommends a discontinuation trial after 6 months of treatment in preschoolers to reassess underlying psychopathology (Gleason 2007). Response may be variable and less robust than that observed in older pediatric patients (Ghuman 2008); 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) (Ghuman 2008).

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 (Ghuman 2008; Greenhill 2006); a small percentage of preschool children may benefit from 1.25 mg 3 times daily (Ghuman 2008). 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 (Greenhill 2006). The 10-month continuation phase trial reported continued or stable clinical improvement at a mean dose of 19.98 mg/day at month 10 (Vitiello 2007).

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 (AACAP [Pliszka 2007])

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.

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 (AACAP [Pliszka 2007])

Adolescents: Usual maximum daily dose: 72 mg/day; however, some patients may require and tolerate daily doses up to 108 mg/day (AACAP [Pliszka 2007])

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 CD: Children ≥6 years and Adolescents: 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 (AACAP [Pliszka 2007])

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 (AAP 2011). 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 (AACAP [Pliszka 2007]).

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

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 (AACAP [Pliszka 2007]). 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.

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 (Arnold 2007). 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 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 (Metadate CD) (Arnold 2007).

Approximate oral methylphenidate equivalents, with a 9-hour patch wear time, for the 20 mg and 30 mg patches are (Arnold 2007):

Approximate oral equivalent daily dose

Patch size (Daytrana)

Immediate release (mg/day)

Osmotic release (eg, Concerta) (mg/day)

15 mg (18.75 cm2)

22.5

27

20 mg (25 cm2)

30

36

30 mg (37.5 cm2)

45

54

Table has been converted to the following text:

15 mg (18.75 cm2) Daytrana patch: Approximate oral equivalent daily dose:

Immediate release: 22.5 mg/day

Osmotic release (eg, Concerta): 27 mg/day

20 mg (25 cm2) Daytrana patch: Approximate oral equivalent daily dose:

Immediate release: 30 mg/day

Osmotic release (eg, Concerta): 36 mg/day

30 mg (37.5 cm2) Daytrana patch: Approximate oral equivalent daily dose:

Immediate release: 45 mg/day

Osmotic release (eg, Concerta): 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

Reconstitution

Suspension: Extended release (Quillivant XR): Prior to dispensing, reconstitute with an appropriate amount of water (refer to bottle).

Administration

Oral:

Controlled-release capsule (Biphentin, Foquest [Canadian products]): Administer in the morning. Swallow whole with full glass of water (Foquest) or with water or other liquid (Biphentin); 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.

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.

IR tablet (Ritalin), IR solution (Methylin), IR chewable tablet (Methylin): Administer each dose 30 to 45 minutes before a meal. Ensure last daily dose is administered before 6 pm if difficulty sleeping occurs. Administer chewable tablet with at least 8 ounces of water or other fluid.

ER capsule (Adhansia XR, Aptensio XR, Jornay PM, Metadate CD, Ritalin LA): Administer with or without food; administer Adhansia XR, Aptensio XR, Metadate CD, and Ritalin LA in the morning and Jornay PM in the evening between 6:30 to 9:30 pm. Alternatively, 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.

ER 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.

ER 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.

ER chewable tablet (QuilliChew ER): Administer in the morning with or without food. Tablets are scored and may be halved.

ER tablet:

Metadate ER: Administer 30 to 45 minutes before a meal. Swallow whole with water or other fluid; do not crush or chew tablet.

Concerta: 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.

Sustained-release tablet (Ritalin-SR): Swallow whole; do not crush or chew tablet.

Topical: 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.

Dietary Considerations

Administer immediate release (IR) tablet (Ritalin), IR solution (Methylin), IR chewable tablet (Methylin), and sustained released tablet (Ritalin-SR) 30-45 minutes before meals. Some products may contain phenylalanine.

Storage

Capsule:

Controlled-release (Biphentin, Foquest [Canadian products]): Store at 15°C to 30°C (59°F to 86°F). Protect from moisture. After sprinkling Foquest on food, the mixture should be used immediately or within 10 minutes of mixing; discard if greater than 10 minutes after mixing.

Extended-release:

Adhansia XR: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light and moisture.

Aptensio XR: Store at 20°C to 25°C (68°F to 77°F). Protect from moisture.

Jornay PM: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from humidity.

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

Ritalin LA: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Solution: Immediate-release (Methylin): Store at 20°C to 25°C (68°F to 77°F).

Suspension: Extended-release (Quillivant XR): Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F), before and after reconstitution. Reconstituted bottle must be used within 4 months.

Tablet:

Extended-release:

Metadate ER: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light and moisture.

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

ER chewable (QuilliChew ER): Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

ER orally disintegrating (Cotempla XR-ODT): Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Store in reusable travel case.

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

IR chewable (Methylin): Store at 20°C to 25°C (68°F to 77°F). Protect from light and moisture.

Sustained-release (Ritalin-SR): Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light and moisture.

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

Drug Interactions

Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Avoid combination

Alcohol (Ethyl): May enhance the adverse/toxic effect of Methylphenidate. Alcohol (Ethyl) may increase the serum concentration of Methylphenidate. Avoid combination

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Monitor therapy

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

Antihypertensive Agents: Methylphenidate may diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

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

Antipsychotic Agents: May enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

CloNIDine: Methylphenidate may enhance the adverse/toxic effect of CloNIDine. 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. Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Esketamine: May enhance the hypertensive effect of CNS Stimulants. Monitor therapy

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

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

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

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

Ioflupane I 123: Methylphenidate may diminish the diagnostic effect of Ioflupane I 123. 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 anticonvulsants. 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 anticonvulsants. 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 anticonvulsants. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of Methylphenidate. Avoid combination

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

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

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

Serotonin Modulators: Methylphenidate may enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy

Solriamfetol: CNS Stimulants may enhance the hypertensive effect of Solriamfetol. Monitor therapy

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

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

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

Test Interactions

May interfere with urine detection of amphetamines/methamphetamines (false-positive).

Adverse Reactions

>10%:

Central nervous system: Insomnia (including initial insomnia; oral: 2% to 33%; transdermal: 6% to 13%), headache (2% to 22%), irritability (6% to 11%)

Endocrine & metabolic: Weight loss (2% to 13%)

Gastrointestinal: Decreased appetite (2% to 28%), xerostomia (oral: 4% to 14%), nausea (2% to 13%)

1% to 10%:

Cardiovascular: Tachycardia (oral: 5%; transdermal: ≤1%), palpitations (oral: 3%; transdermal: <1%), increased blood pressure (≥2%), increased heart rate (oral: ≥2%)

Central nervous system: Emotional lability (1% to 9%), anxiety (oral: 8%), jitteriness (oral: 3% to 8%), increased diastolic blood pressure (oral: 7%), tic disorder (transdermal: 7%; oral: 2%), dizziness (2% to 7%), psychomotor agitation (oral: 5%), depressed mood (oral: 4%), nervousness (oral: 3%; transdermal: <1%), restlessness (oral: 3%), aggressive behavior (oral: 2%), agitation (oral: 2%), depression (≤2%), hypertonia (oral: 2%), lack of emotion (oral: 2%), vertigo (oral: 2%), confusion (oral: 1%), sedated state (oral: 1%), tension (oral: 1%), tension headache (oral: 1%), paresthesia (≤1%)

Dermatologic: Hyperhidrosis (oral: 5%), excoriation of skin (oral: 4%), skin rash (oral: 2%)

Endocrine & metabolic: Decreased libido (oral: 2%)

Gastrointestinal: Vomiting (1% to 10%), abdominal pain (transdermal: 5% to 7%), diarrhea (oral: 3% to 7%), upper abdominal pain (oral: 4% to 6%), anorexia (2% to 5%), bruxism (oral: 2%), dyspepsia (oral: 2%), motion sickness (oral: 2%), constipation (oral: 1%)

Hematologic & oncologic: Bruise (oral: 3%)

Neuromuscular & skeletal: Back pain (oral: 3%), tremor (oral: 3%)

Ophthalmic: Blurred vision (≤2%), eye pain (oral: 2%)

Respiratory: Upper respiratory tract infection (oral: 2% to 4%), nasopharyngitis (oral: 3%), streptococcal pharyngitis (oral: 3%), cough (oral: 2%), oropharyngeal pain (oral: 1% to 2%)

Miscellaneous: Fever (oral: 2%)

Frequency not defined:

Cardiovascular: Cardiac arrhythmia, decreased blood pressure, decreased pulse, heart murmur, hypertension, increased pulse

Central nervous system: Delirium, drug abuse, drug dependence, Gilles de la Tourette syndrome (rare), hypervigilance, hypomania, mood changes, outbursts of anger, panic attack, sleep disorder, toxic psychosis

Dermatologic: Macular eruption

Endocrine & metabolic: Growth retardation, hot flash, increased thirst

Gastrointestinal: Abdominal distress, viral gastroenteritis

Genitourinary: Erectile dysfunction

Hematologic & oncologic: Anemia, leukopenia

Hepatic: Increased serum alanine aminotransferase

Infection: Viral infection

Neuromuscular & skeletal: Asthenia, muscle spasm

Ophthalmic: Dry eye syndrome

Respiratory: Bronchitis, dyspnea, sinusitis

<1%, postmarketing, and/or case reports: Accommodation disturbance, allergic contact dermatitis, alopecia, anaphylaxis, angina pectoris, angioedema, application site reaction, arthralgia, auditory hallucination, bradycardia, bullous skin disease, cerebral arteritis, cerebrovascular occlusion, change in libido, change in WBC count, chest discomfort, chest pain, contact hypersensitivity, diplopia, disorientation, drowsiness, drug tolerance, dyskinesia, erythema of skin, erythema multiforme, exfoliative dermatitis, extrasystoles, fatigue, hallucination, hepatic failure (acute), hepatic injury (severe), hyperpyrexia, hypersensitivity reaction, immune thrombocytopenia, increased liver enzymes, increased serum alkaline phosphatase, increased serum bilirubin, lethargy, leukoderma (chemical; FDA Safety Alert 2015), loss of scalp hair, mania, muscle twitching, myalgia, mydriasis, necrotizing angiitis, neuroleptic malignant syndrome, pancytopenia, peripheral vascular insufficiency, priapism, pruritus, Raynaud disease, rhabdomyolysis, seizure, supraventricular tachycardia, swelling of the ear, talkativeness, thrombocytopenia, urticaria, ventricular arrhythmia (Schelleman 2012), ventricular premature contractions, visual disturbance, visual hallucination, visual impairment

ALERT: U.S. Boxed Warning

Abuse and dependence:

CNS stimulants, including methylphenidate-containing products and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy.

Long-term abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during withdrawal from abusive use because severe depression may occur. Withdrawal following long-term therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular events: CNS stimulant treatment has been associated with sudden death in children and adolescents with preexisting structural cardiac abnormalities and sudden death, stroke, and myocardial infarction (MI) have been reported in adults. Consistent with other studies, a large retrospective cohort study involving 1,200,438 children, adolescents, and young adults (aged 2 to 24 years) prescribed methylphenidate, dexmethylphenidate, dextroamphetamines, amphetamine salts, pemoline, or atomoxetine found no evidence that current use of an attention-deficit/hyperactivity disorder (ADHD) medication increased risk for sudden cardiac death, acute MI, or stroke (Cooper 2011). Stimulants should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, Marfan syndrome, or other serious cardiac problems. Some products are contraindicated in patients with moderate or severe hypertension, angina, heart failure, arrhythmias, or recent MI. Prior to initiating stimulant, assess medical history and family history of sudden death or ventricular arrhythmia; conduct a physical exam to assess for cardiac disease; patients should receive further evaluation if findings suggest cardiac disease, such as ECG and echocardiogram. Promptly conduct cardiac evaluation in patients who develop exertional chest pain, unexplained syncope, or any other symptoms of cardiac disease during methylphenidate treatment.

• Hypersensitivity: Hypersensitivity reactions, such as angioedema and anaphylactic reactions have been reported.

• 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 rarely; monitor for digital changes during therapy and refer for further evaluation (eg, rheumatology) if necessary.

• Priapism: Prolonged (>4 hours), painful, and nonpainful erections, sometimes requiring surgical intervention, have been reported in pediatric and adult patients, according to the manufacturers' labeling and a 2013 FDA warning; there are at least 22 published cases (Baytunca 2016; Bozkurt 2017; Chauhan 2016; Eiland 2014; Esnafoglu 2017; Mann 2017; Unver 2017). Priapism has been reported to develop after some time on the drug, often subsequent to an increase in dose but also during a period of drug withdrawal (drug holidays or discontinuation). Patients with certain hematological dyscrasias (eg, sickle cell disease), malignancies, perineal trauma, or concomitant use of alcohol, illicit drugs, or other medications associated with priapism may be at increased risk (Eiland 2014). Patients who develop abnormally sustained or frequent and painful erections should discontinue therapy and seek immediate medical attention. An emergent urological consultation should be obtained in severe cases. Priapism has been associated with different dosage forms and products; it is not known if rechallenge with a different formulation will risk recurrence. In patients with severe cases of priapism that were slow to resolve and/or required detumescence by aspiration, avoidance of stimulants and atomoxetine may be preferred (Eiland 2014).

• Visual disturbance: Difficulty in accommodation and blurred vision have been reported with the use of stimulants.

Disease-related concerns:

• Abuse potential: [US Boxed Warning]: CNS stimulants, including methylphenidate-containing products and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Long-term abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during withdrawal from abusive use because severe depression may occur. Withdrawal following long-term therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.

• Cardiovascular disorders: CNS stimulants may increase heart rate and blood pressure; in pediatric patients, the observed mean increase in heart rate was 3 to 6 bpm and blood pressure was 2 to 4 mm Hg. Use with caution in patients with hypertension, heart failure, recent MI, ventricular arrhythmia, and other cardiovascular conditions that might be exacerbated by increases in blood pressure or heart rate. Some products are contraindicated in patients with severe hypertension, hyperthyroidism, or angina.

• Psychiatric disorders: Use with caution in patients with preexisting psychosis (may exacerbate symptoms of behavior and thought disorder) or bipolar disorder (may induce mixed/manic episode). New-onset psychosis or mania may occur with stimulant use. Patients should be screened for bipolar disorder and risk factors for developing a manic episode prior to treatment; consider discontinuation if psychotic or manic symptoms (eg, delusional thinking, hallucinations, mania) occur. May be associated with aggressive behavior or hostility in children (causal relationship not established); monitor for development or worsening of these behaviors. 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 (Huang 2018; Man 2017). Monitor for suicide-related behavior.

• 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Use of stimulants has been associated with appetite suppression, weight loss, and slowing of growth rate; monitor growth rate, height, and weight during treatment. Treatment interruption may be necessary in patients who are not increasing in height or gaining weight as expected.

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: 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).

• Metadate CD: Concomitant use with halogenated anesthetics is contraindicated; may cause sudden elevations in blood pressure; if surgery is planned, do not administer Metadate CD on the day of surgery.

• 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.

Monitoring Parameters

Periodic CBC, differential, and platelet counts with prolonged use; blood pressure, heart rate; signs and symptoms of depression, aggression, hostility, suicidal behavior/ideation; growth rate (height and weight) in children; signs of central nervous system stimulation; signs of peripheral vasculopathy (eg, digital changes)

Transdermal: Signs of worsening erythema, blistering or edema which does not improve within 48 hours of patch removal, or spreads beyond patch site.

When used for the treatment of ADHD, thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure, and consider obtaining ECG prior to initiation (Vetter 2008).

Pregnancy Considerations

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.

Patient Education

What is this drug used for?

• It is used to treat attention deficit problems with hyperactivity and to treat narcolepsy. It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea

• Vomiting

• Rhinitis

• Pharyngitis

• Fatigue

• Dry mouth

• Weight loss

• Anxiety

• Lack of appetite

• Insomnia

• Heartburn

• Skin irritation

• Abdominal pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight

• Serotonin syndrome like dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea

• Infection

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice

• Chest pain

• Severe dizziness

• Passing out

• Vision changes

• Shortness of breath

• Joint pain

• Purple patches on skin or mouth

• Tachycardia

• Bradycardia

• Abnormal heartbeat

• Severe headache

• Seizures

• Tremors

• Abnormal movements

• Sweating a lot

• Bruising

• Bleeding

• Severe loss of strength and energy

• Agitation

• Change in color of hands or feet from pale to blue or red

• Numbness or tingling of hands or feet

• Painful extremities

• Cold sensation of extremities

• Wounds on fingers or toes

• Urinary retention

• Muscle pain

• Muscle weakness

• Dark urine

• Libido changes

• Priapism

• Skin discoloration

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion

• Hallucinations

• Mood changes

• Behavioral changes

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Related questions

Hide