Brand names: Aptensio, Concerta, Cotempla, Daytrana, Jornay, ... show all 10 brands Methylin, QuilliChew, Quillivant, Relexxii, Ritalin
Drug class: Respiratory and CNS Stimulants

Medically reviewed by Drugs.com on Sep 10, 2025. Written by ASHP.

Introduction

Piperidine-derivative; CNS stimulant.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

Uses for Methylphenidate

Attention Deficit Hyperactivity Disorder (ADHD)

Used orally (as methylphenidate hydrochloride immediate-release conventional tablets [Ritalin], oral solution [Methylin], and chewable tablets; also, as extended-release oral suspension [Quillivant XR], tablets, capsules [Aptensio XR], chewable tablets [Quillichew ER], and delayed- and extended-release capsules [Jornay PM]) for the treatment of ADHD in adults and pediatric patients ≥6 years of age.^{114 145 152 157 158 168 170 171}

Used orally (as methylphenidate hydrochloride extended-release trilayer core tablets [Concerta] and bilayer core tablets [Relexxii] for the treatment of ADHD in adults ≤65 years of age and pediatric patients ≥6 years of age.^{118 553}

Used orally (as methylphenidate hydrochloride CD extended-release capsules [generic equivalent of Metadate CD]) for the treatment of ADHD in pediatric patients 6–15 years of age.¹²⁵

Used orally (as methylphenidate hydrochloride extended-release capsules [Ritalin LA]) for the treatment of ADHD in pediatric patients 6–12 years of age.¹²⁹

Used orally (as methylphenidate extended-release orally disintegrating tablets [Cotempla XR-ODT]) and transdermally (as methylphenidate transdermal system [Daytrana]) for the treatment of ADHD in pediatric patients between 6–17 years of age.^{147 172}

Safety and efficacy in children <6 years of age^{† [off-label]} not established, but has been evaluated in several controlled clinical studies in children up to 6 years of age.^{140 512 556}

The American Academy of Pediatrics (AAP) has developed guidelines for children and adolescents with ADHD.⁵⁰⁰ For pediatric patients 6–12 years of age, an FDA-approved drug for ADHD should be prescribed, in addition to parent training in behavior management (PTBM) and/or behavioral classroom interventions.⁵⁰⁰ For choice of medication, evidence is particularly strong for stimulant medications (e.g., methylphenidate).⁵⁰⁰ For adolescents 12–18 years, an FDA-approved drug should be prescribed with the adolescent's assent.⁵⁰⁰ Behavioral and other evidence-based training interventions should also be prescribed if available.⁵⁰⁰

AAP states that methylphenidate may be considered for treatment of ADHD in preschool-aged children^{† [off-label]} (4 years of age to the sixth birthday) if first-line treatments (i.e., PTBM and/or behavioral classroom interventions) do not provide substantial improvement and there is continued moderate to severe disturbance in the child's functioning.⁵⁰⁰

International experts have published recommendations for the treatment of ADHD in adults.^{506 559} Treatment of ADHD in adults should follow a multimodal approach that includes psychoeducation, pharmacotherapy, cognitive behavior therapy, and coaching for ADHD.⁵⁰⁶ First-line pharmacotherapy agents include long-acting stimulants such as mixed amphetamine salts, methylphenidate, and lisdexamfetamine.⁵⁵⁹

Narcolepsy

Used orally (as methylphenidate hydrochloride immediate-release conventional tablets [Ritalin], oral solution [Methylin], chewable tablets, and extended-release tablets) for the treatment of narcolepsy.^{114 145 152 158}

The American Academy of Sleep Medicine (AASM) provides a strong recommendation for the use of several agents for the treatment of narcolepsy in adults, including modafinil, pitolisant, sodium oxybate, and solriamfetol.⁵⁶⁰ A conditional recommendation is given for armodafinil, dextroamphetamine, and methylphenidate.⁵⁶⁰

Autism Spectrum Disorder (ASD)† [off-label]

Has been used for the symptomatic treatment of inattention, impulsivity, and hyperactivity in pediatric patients 6-18 years of age with ASD.^{562 563}

Guidelines from AAP suggest the use of psychostimulants (e.g., methylphenidate, dexmethylphenidate, mixed amphetamine salts, lisdexamfetamine, dextroamphetamine) for symptoms of hyperactivity, impulsivity, inattention, and distractibility in pediatric patients with ASD if problems persist after behavioral interventions.⁵⁶³ Patients should start with a low dose, with increases as needed and tolerated.⁵⁶³ Stimulants may be most effective in children who do not have a comorbid intellectual disability.⁵⁶³

Amphetamine-type Stimulant Use Disorder† [off-label]

Has been used for the treatment of amphetamine-type stimulant use disorder.⁵⁶⁴

American Society of Addiction Medicine (ASAM) and American Academy of Addiction Psychiatry (AAAP) guidelines state that long-acting methylphenidate may be considered as a treatment option to reduce use of amphetamine-type stimulants.⁵⁶⁴ For patients with a moderate or higher frequency of use of amphetamine-type stimulants (i.e., ≥10 days per month) or for patients with co-occurring ADHD, long-acting methylphenidate can be given additional consideration.⁵⁶⁴

Idiopathic Hypersomnia† [off-label]

Has been used for the treatment of idiopathic hypersomnia.^{560 561}

AASM guidelines state that methylphenidate (versus no treatment) is suggested for the treatment of idiopathic hypersomnia in adults.⁵⁶⁰

Methylphenidate Dosage and Administration

General

Pretreatment Screening

• Evaluate pediatric patients and adults for cardiac disease (i.e., obtain careful medical history, perform physical examination, and screen for family history of sudden death or ventricular arrhythmias).^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Screen for a family history and clinically evaluate for motor or verbal tics or Tourette’s syndrome prior to initiating therapy.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Because CNS stimulants, including methylphenidate, have a high potential for abuse and dependence, assess the risk of abuse, misuse, and addiction prior to initiating therapy.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Screen for pre-existing psychotic or manic symptoms/illness, risk factors for developing a manic episode (comorbid or history of depressive symptoms or family history of suicide, bipolar disorder, or depression.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Due to the risk of GI obstruction with methylphenidate extended-release bilayer and trilayer core tablets (e.g., Relexxii, Concerta, generics), screen for pre-existing esophageal motility disorders, small bowel inflammatory disease, short gut syndrome, past history of peritonitis, cystic fibrosis, chronic intestinal pseudo-obstruction, or Meckel's diverticulum.^{118 553}

• Because QuilliChew ER contains phenylalanine, consider total combined daily amount of phenylalanine from all sources prior to initiating in patients with phenylketonuria.¹⁷¹

Patient Monitoring

• Routinely monitor patients receiving methylphenidate therapy for the emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically needed.^{114 118 125 129 145 147 152 157 158 168}

• Monitor patients receiving stimulants for signs of abuse, misuse, and addiction during therapy.^{114 118 125 129 145 147 152 157 158 168}

• Monitor all patients for the development of hypertension and tachycardia.^{114 118 125 129 145 147 152 157 158 168}

• Periodic monitoring of CBC, differential, and platelet counts are recommended during prolonged therapy.^{118 147 152}

• Closely monitor growth (height and weight) in children receiving methylphenidate therapy.^{114 118 125 129 145 147 152 157 158 168}

• Closely monitor patients with a history of increased intraocular pressure (IOP) or open angle glaucoma for ophthalmologic changes.^{114 118 125 129 145 147 152 157 158 168}

• Monitor patients receiving the methylphenidate transdermal system for loss of skin pigmentation, especially at application sites.¹⁶³

• Monitor for the emergence of seizures.^{118 152 553}

• Monitor for digital changes due to risk of Raynaud's phenomenon.^{114 118 125 129 145 147 152 157 158 168}

• Monitor for the emergence or worsening of psychotic or manic symptoms/episodes.^{114 118 125 129 145 147 152 157 158 168}

Dispensing and Administration Precautions

Handling and Disposal

• Methylphenidate should be disposed of by a medicine take-back program at a U.S. Drug Enforcement Administration (DEA) authorized collection site when it is no longer needed.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} If there is no take-back program or authorized DEA collection site available, the drug can be mixed with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds and disposed of in a sealed plastic bag in the household trash.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} After removal of a methylphenidate transdermal system, fold used systems so that the adhesive side adheres to itself and then flush down the toilet or dispose of in an appropriate lidded container.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} Any unused systems that are no longer needed should be removed from their packaging, separated from the protective liner, folded so that the adhesive side adheres to itself, and then flushed down the toilet or disposed of in an appropriate lidded container.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• The Institute for Safe Medication Practices (ISMP) includes methylphenidate and methadone on their List of Confused Drug Names, and recommends using special safeguards to ensure the accuracy of prescriptions for these drugs.⁵⁵⁵

Administration

Administer orally^{114 118 125 129 145 152 157 158 168 553} or percutaneously by topical application of a transdermal system.¹⁴⁷

Oral Administration

Immediate-release Preparations (Conventional Tablets, Chewable Tablets, or Oral Solution)

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

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

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

Administer chewable tablets with a full glass (i.e., ≥240 mL [8 ounces]) of water or other fluid to avoid choking.¹⁵²

Extended-release Tablets (Generics)

Swallow tablets whole; do not crush or chew.¹⁵⁸

May be used when the 8-hour dosage of the extended-release preparation corresponds to the titrated 8-hour dosage of the conventional tablets.¹⁵⁸

Administer 30–45 minutes before a meal.¹⁵⁸

Extended-release Trilayer (Concerta; Generics) and Bilayer (Relexxii) Core Tablets

Administer once daily in the morning without regard to meals.^{118 553}

Swallow tablets whole; do not crush, divide, or chew.^{118 553}

Extended-release Orally Disintegrating Tablets (Cotempla XR-ODT)

Administer once daily in the morning in a consistent manner relative to food intake.¹⁷²

Administer immediately following removal from the blister package; do not save for later use.¹⁷² Remove tablet from blister package with dry hands by peeling back the foil and not by pushing the tablet through the foil.¹⁷² Place tablet on patient's tongue and allow to disintegrate in saliva without chewing or crushing.¹⁷² Administration of liquid with the tablet is not required.¹⁷²

Powder for Extended-release Suspension (Quillivant XR)

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

Must be reconstituted prior to dispensing.¹⁵⁷

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

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

Keep bottle tightly closed and vigorously shake for ≥10 seconds before each use.¹⁵⁷

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

Extended-release Capsules (Aptensio XR, Ritalin LA; Generics, including Equivalents of Metadate CD [Methylphenidate Hydrochloride CD])

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

Manufacturer states that methylphenidate hydrochloride CD extended-release capsules should be administered before breakfast.¹²⁵ Manufacturer states that administration of Ritalin LA relative to timing and composition of meals may need to be individually adjusted.¹²⁹ The manufacturer states Aptensio XR may be administered without regard to meals, but should be administered in a consistent manner relative to food intake.¹⁶⁸

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

Alternatively, open capsule and sprinkle contents on a small amount (e.g., one tablespoonful) of applesauce; swallow immediately (or within 10 minutes for Aptensio XR) without chewing.^{125 129 168} Manufacturer states that contents of Ritalin LA capsules should not be mixed with warm applesauce because release properties of the formulation could be affected.¹²⁹

One manufacturer suggests that patient should drink fluids immediately after swallowing the intact capsule or sprinkle/applesauce mixture.¹²⁵

Patients receiving extended-release capsules should avoid consuming alcohol; alcohol may result in more rapid release of drug from these formulations.^{125 129 168}

If a dose is missed, resume the regular schedule the following morning; do not administer the missed dose later in the day and do not administer an extra dose to make up for the missed dose.¹⁶⁸

Delayed- and Extended-release Capsules (Jornay PM)

Jornay PM (methylphenidate hydrochloride) capsules exhibit both delayed-release and extended-release properties.¹⁷⁰ Administer once daily in the evening in a consistent manner relative to food intake.¹⁷⁰

If a dose is missed, administer the missed dose the same evening as soon as it is remembered; if the missed dose is not remembered until the following morning, omit the missed dose and administer the next dose at the regularly scheduled time.¹⁷⁰ Doses should not be administered in the morning.¹⁷⁰

Initially, administer at 8:00 p.m.; adjust administration time within the range of 6:30–9:30 p.m. to optimize tolerability and efficacy the next morning and throughout that day.¹⁷⁰ Once administration time has been optimized, administer at the same time each day.¹⁷⁰ In clinical trials in children 6–12 years of age, >70% of patients received the drug at 8 p.m.¹⁷⁰

Swallow capsules whole.¹⁷⁰

Alternatively, open capsule and sprinkle entire contents onto applesauce; swallow immediately without chewing.¹⁷⁰

Transdermal Administration (Daytrana)

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

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

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

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

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

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

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

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

Encourage parents or caregiver to record and monitor the application and removal times and method of disposal for each system.¹⁴⁷ If a system was removed without the parent’s or caregiver’s knowledge or if a system is missing from the tray, the parent or caregiver should be encouraged to ask the child when and how the system was removed.¹⁴⁷

Dosage

Available as methylphenidate (transdermal) and methylphenidate hydrochloride (oral); dosage of transdermal systems is expressed in terms of methylphenidate, and dosage of oral formulations generally is expressed in terms of the salt.^{114 118 125 129 145 147 157 158 168 170 171} However, dosage of methylphenidate hydrochloride extended-release orally disintegrating tablets (Cotempla XR-ODT) is expressed in terms of methylphenidate; each 8.6, 17.3, or 25.9 mg of methylphenidate is equivalent to 10, 20, or 30 mg, respectively, of methylphenidate hydrochloride.¹⁷²

Carefully adjust dosage according to individual requirements and response.¹⁵²

Some patients receiving longer-acting preparations may require supplemental therapy with an immediate-release formulation of the drug to increase the efficacy, particularly in the morning, or to extend the duration of therapeutic effects later in the day.¹³⁷

Discontinue therapy if a beneficial effect is not attained after appropriate dosage adjustment over 1 month.^{114 118 145 152 158 171}

If paradoxical aggravation of symptoms occurs, reduce dosage or discontinue the drug.^{114 118 145 152 158 171}

Periodically reevaluate long-term usefulness and adjust dosage as needed.¹¹⁴

Pediatric Patients

ADHD

Extended-release oral formulations may contain both immediate-release and extended-release methylphenidate in various proportions, generally ranging from 20% immediate-release and 80% extended-release drug to equal proportions of each preparation in various delivery systems.^{125 129 157 168 171 172} Differences in methylphenidate preparations (e.g., method of drug delivery, drug release characteristics, onset and duration of activity, ease of administration) allow for individualization of therapy based on patient needs.

Initial Therapy with Immediate-release Preparations (Conventional Tablets, Chewable Tablets, or Oral Solution)

Oral

Pediatric patients ≥6 years of age: Initially, 5 mg twice daily, before breakfast and lunch.^{114 145 152} Increase dosage by 5–10 mg daily at weekly intervals based on response and tolerance, up to 60 mg daily; administer daily dosage in 2 or 3 divided doses.^{114 145 152} Duration of action is approximately 3–4 hours. ⁵¹⁰

Switching to Extended-release Tablets (Generics)

Oral

Pediatric patients ≥6 years of age: Extended-release tablets can be substituted for conventional tablets when the 8-hour dosage of methylphenidate hydrochloride as extended-release tablets corresponds to the titrated 8-hour dosage of the drug administered as conventional tablets.¹⁵⁸

Initial Therapy with Extended-release Chewable Tablets (QuilliChew ER)

Oral

Pediatric patients ≥6 years of age: Initially, 20 mg once daily in the morning.¹⁷¹ Clinical studies suggest duration of action is 8–12 hours.^{171 510} Adjust dosage by 10, 15, or 20 mg daily at weekly intervals, up to 60 mg daily.¹⁷¹ Dosages of 10 and 15 mg may be attained by halving the functionally scored 20 and 30 mg tablets, respectively.¹⁷¹

Switching to Extended-release Chewable Tablets (QuilliChew ER)

Oral

Pediatric patients ≥6 years of age: Do not substitute for other methylphenidate preparations on mg-for-mg basis because of different methylphenidate base compositions and pharmacokinetic profiles.¹⁷¹ In patients being transferred from other methylphenidate formulations, use same initial dosage and follow same dosage titration schedule recommended for patients receiving extended-release chewable tablets as their initial methylphenidate regimen.¹⁷¹

Initial Therapy with Extended-release Trilayer (Concerta; Generics) or Bilayer (Relexxii) Core Tablets

Oral

Pediatric patients 6–17 years of age: Initially, 18 mg once daily in the morning.^{118 553} Duration of action of trilayer core tablets (Concerta) is approximately 10–12 hours.¹¹⁸ Duration of action of bilayer core tablets (Relexxii) is approximately 8-12 hours.⁵⁵³ If adequate response does not occur, increase dosage at weekly intervals in increments of 18 mg daily up to 54 mg daily in children 6–12 years of age or 72 mg daily (maximum 2 mg/kg daily) in adolescents 13–17 years of age.^{118 553}

Switching to Extended-release Trilayer (Concerta; Generics) or Bilayer (Relexxii) Core Tablets

Oral

For manufacturer's recommendations for switching from conventional methylphenidate preparations to extended-release trilayer or bilayer core tablets, see Table 1.^{118 553}

Initial dosage as extended-release trilayer or bilayer core tablets in patients being switched from conventional tablets should not exceed 72 mg daily.^{118 553} Adjust dosage at weekly intervals in increments of 18 mg daily, up to 54 mg daily in children 6–12 years of age and 72 mg (maximum 2 mg/kg) daily in adolescents.^{118 553}

A 27-mg extended-release trilayer core tablet is available for patients who require a dosage in between 18 mg daily and 36 mg daily.¹¹⁸ Several bilayer tablet strengths (27 mg, 45 mg, and 63 mg) are also available for in-between dosages during titration.⁵⁵³

Initial Therapy with Extended-release Orally Disintegrating Tablets (Cotempla XR-ODT)

Oral

Pediatric patients 6–17 years of age: Initially, 17.3 mg of methylphenidate (equivalent to 20 mg of methylphenidate hydrochloride) once daily in the morning.¹⁷² Adjust dosage by 8.6–17.3 mg daily at weekly intervals, up to 51.8 mg daily (equivalent to 60 mg of methylphenidate hydrochloride daily).¹⁷² Duration of action is approximately 12 hours.¹⁷²

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

Oral

Pediatric patients ≥6 years of age: Initially, 20 mg once daily in the morning.¹⁵⁷ Increase dosage by 10–20 mg daily at weekly intervals, up to 60 mg daily.¹⁵⁷ Duration of action is approximately 10–12 hours.^{157 510}

Switching to Extended-release Oral Suspension (Quillivant XR)

Oral

Pediatric patients ≥6 years of age: Do not substitute for other methylphenidate preparations on mg-for-mg basis because of different methylphenidate base compositions and pharmacokinetic profiles.¹⁵⁷ In patients being transferred from other methylphenidate formulations, use same initial dosage and follow same dosage titration schedule recommended for patients receiving extended-release suspension as their initial methylphenidate regimen.¹⁵⁷

Initial Therapy with Extended-release Capsules (Aptensio XR, Methylphenidate Hydrochloride CD, Ritalin LA; Other Generics)

Oral

Aptensio XR or generic equivalents in pediatric patients ≥6 years of age: Initially, 10 mg once daily in the morning.¹⁶⁸ Increase dosage by 10 mg daily at weekly intervals, up to 60 mg daily.¹⁶⁸ Duration of action is approximately 12 hours.^{168 510}

Methylphenidate hydrochloride CD in pediatric patients ≥6 years of age: Initially, 20 mg once daily in the morning.¹²⁵ Increase dosage by 10–20 mg daily at weekly intervals, up to 60 mg daily.¹²⁵ Duration of action is approximately 6–8 hours.

Ritalin LA in children 6–12 years of age: Initially, 20 mg once daily in the morning.¹²⁹ Alternatively, initiate with 10 mg once daily when a lower initial dosage is appropriate.¹²⁹ Increase dosage by 10 mg daily at weekly intervals, up to 60 mg daily.¹²⁹ Duration of action is approximately 6–8 hours.

Switching to Extended-release Capsules (Ritalin LA; Generics)

Oral

For manufacturer's recommendations for switching from conventional or extended-release methylphenidate hydrochloride tablets to Ritalin LA in children 6–12 years of age, see Table 2.¹²⁹

Do not substitute for other methylphenidate preparations on mg-for-mg basis because of different methylphenidate base compositions and pharmacokinetic profiles.¹²⁹ In patients being transferred from therapy with other methylphenidate formulations, use same initial dosage and follow same dosage titration schedule recommended for patients receiving Ritalin LA as their initial methylphenidate regimen.¹²⁹

Initial Therapy with Delayed- and Extended-release Capsules (Jornay PM)

Oral

Pediatric patients 6–17 years of age: Initially, 20 mg once daily in the evening.¹⁷⁰ Adjust dosage by 20 mg daily at weekly intervals, up to 100 mg daily.¹⁷⁰ Following an initial delay in absorption of approximately 8–10 hours,^{170 173 510} duration of clinical response is approximately 10–12 hours. ⁵¹⁰

Switching to Delayed- and Extended-release Capsules (Jornay PM)

Oral

Do not substitute for other methylphenidate preparations on mg-for-mg basis because of different methylphenidate base compositions and pharmacokinetic profiles.¹⁷⁰ In patients being transferred from therapy with other methylphenidate formulations, use same initial dosage and follow same dosage titration schedule recommended for patients receiving delayed- and extended-release capsules as their initial methylphenidate regimen.¹⁷⁰

Initial Therapy with or Switching to Transdermal System

Transdermal

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

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

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

Adults

ADHD

Extended-release formulations are used more commonly,⁵¹⁰ but may initiate therapy in some patients with an immediate-release formulation to assess tolerability and determine approximate dosage requirements.⁵¹⁰

Extended-release oral formulations may contain both immediate-release and extended-release methylphenidate in various proportions, generally ranging from 20% immediate-release and 80% extended-release drug to equal proportions of each preparation in various delivery systems.^{125 129 157 168 171 172} Differences in methylphenidate preparations (e.g., method of drug delivery, drug release characteristics, onset and duration of activity, ease of administration) allow for individualization of therapy based on patient needs.

Therapy with Immediate-release Preparations (Conventional Tablets, Chewable Tablets, or Oral Solution)

Oral

Usual dosage is 20–30 mg administered in 2 or 3 divided doses daily, up to 60 mg daily.^{114 145 152} Some patients may require 40–60 mg daily, while others may require only 10–15 mg daily.^{145 152}

Switching to Extended-release Tablets (Generics)

Oral

Extended-release tablets can be substituted for conventional tablets when the 8-hour dosage of methylphenidate hydrochloride as extended-release tablets corresponds to the titrated 8-hour dosage of the drug administered as conventional tablets.¹⁵⁸

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

Initial Therapy with Extended-release Chewable Tablets (QuilliChew ER)

Oral

Initially, 20 mg once daily in the morning.¹⁷¹ Duration of action is 8–12 hours.^{171 510} Adjust dosage by 10, 15, or 20 mg daily at weekly intervals, up to 60 mg daily.¹⁷¹ Functionally scored 20 mg and 30 mg tablets can be broken to achieve 10-mg and 15-mg doses.¹⁷¹

Switching to Extended-release Chewable Tablets (QuilliChew ER)

Oral

Do not substitute for other methylphenidate preparations on mg-for-mg basis because of different methylphenidate base compositions and pharmacokinetic profiles.¹⁷¹ In patients being transferred from other methylphenidate formulations, use same initial dosage and follow same dosage titration schedule recommended for patients receiving extended-release chewable tablets as their initial methylphenidate regimen.¹⁷¹

Initial Therapy with Extended-release Trilayer (Concerta; Generics) or Bilayer (Relexxii) Core Tablets

Oral

Initially, 18 or 36 mg once daily in the morning.^{118 553} Duration of action of Concerta is approximately 10–12 hours.¹¹⁸ Duration of action of Relexxii is approximately 8–12 hours.⁵⁵³ If adequate response does not occur, increase dosage by 18 mg daily at weekly intervals, up to 72 mg daily.^{118 553}

Switching to Extended-release Trilayer (Concerta; Generics) or Bilayer (Relexxii) Core Tablets

Oral

For manufacturer's recommendations for switching from conventional methylphenidate preparations to extended-release trilayer or bilayer core tablets, see Table 3.¹¹⁸

Initial dosage as extended-release trilayer or bilayer core tablets in patients being switched from conventional tablets should not exceed 72 mg daily.^{118 553} Adjust dosage at weekly intervals in increments of 18 mg daily, up to 72 mg daily.^{118 553}

A 27-mg extended-release trilayer core tablet also is available for patients who require a dosage in between 18 mg daily and 36 mg daily.¹¹⁸ Several bilayer tablet strengths (27 mg, 45 mg, and 63 mg) are also available for in-between dosages during titration.⁵⁵³

Narcolepsy

Oral

Usual dosage of 10 mg (as conventional tablets or oral solution) 2 or 3 times daily; some patients require 40–60 mg daily, in others, 10-15 mg daily may be adequate.^{114 145 152}

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

Renal Impairment

No specific dosage recommendations at this time.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

Geriatric Patients

No specific dosage recommendations at this time.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} Generally, dosage selection for geriatric patients should start at the lower end of the dosage range, reflecting the greater frequency of reduced hepatic, renal, or cardiac function and of concomitant diseases and drug therapy.¹⁶⁸

Cautions for Methylphenidate

Contraindications

• Known hypersensitivity to methylphenidate or any ingredient in the formulation.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Concomitant or recent (within 14 days) administration of monoamine oxidase (MAO) inhibitors since hypertensive crisis could result.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Some methylphenidate hydrochloride extended-release capsules may contain sucrose and should not be used in patients with hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency.¹²⁵

Warnings/Precautions

Warnings

Abuse, Misuse, and Addiction

High potential for abuse, misuse, and addiction with methylphenidate.^{114 118 125 129 145 147 152 157 158 168} (See Boxed Warning). In addition, the drug can be diverted for nonmedical use into illicit channels or distribution.^{114 118 125 129 145 147 152 157 168 170 171 172 553} Assess risk of abuse, misuse, and addiction prior to initiating therapy and monitor for signs of abuse, misuse, and addiction during therapy.^{114 118 125 129 145 147 152 157 158 168} Misuse and abuse of CNS stimulants can result in overdosage and death.^{114 118 125 129 145 147 152 157 158 168} During long-term CNS stimulant therapy, tolerance can also develop.^{114 118 125 129 145 147 152 157 158 168} Abuse by unintended routes of administration (e.g., chewing, snorting, or injecting formulation) can increase the risk of overdosage and death.^{114 118 125 129 145 147 152 157 158 168} Abrupt cessation of therapy, rapid dosage reduction, or administration of an antagonist in patients physically dependent on CNS stimulants may result in withdrawal syndrome (e.g., dysphoric mood, fatigue, vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite, psychomotor retardation or agitation).^{114 118 125 129 145 147 152 157 158 168} Advise patients and/or caregivers that methylphenidate can be abused and result in dependence.^{114 118 125 129 145 147 152 157 158 168} The drug must be store in a safe (preferably locked) location to prevent abuse and misuse.^{114 118 125 129 145 147 152 157 158 168} Dispose of the drug at a medicine take-back program at a U.S. Drug Enforcement Administration (DEA) authorized collection site when it is no longer needed.^{114 118 125 129 145 147 152 157 158 168} If there is no take-back program or authorized DEA collection site available, the drug can be mixed with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds and disposed of in a sealed plastic bag in the household trash.^{114 118 125 129 145 147 152 157 158 168}

Other Warnings and Precautions

Risks to Patients with Serious Cardiac Disease

Sudden unexplained death, stroke, and MI reported in patients with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of stimulants for ADHD treatment.^{114 118 125 129 145 147 152 157 158 168}

Thoroughly review medical history (including evaluation for family history of sudden death or ventricular arrhythmia) and perform physical examination in all children, adolescents, and adults being considered for stimulant therapy.^{114 118 125 129 145 147 152 157 158 168}

In general, avoid use of CNS stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, CAD, or other serious cardiac conditions.^{114 118 125 129 145 147 152 157 158 168}

Patients who develop exertional chest pain, unexplained syncope, or other manifestations suggestive of cardiac disease during stimulant therapy should undergo prompt cardiac evaluation.^{114 118 125 129 145 147 152 157 158 168}

Increased BP and Heart Rate

Possible modest increases in average BP (i.e., by about 2–4 mm Hg) and heart rate (i.e., by about 3–6 bpm); larger increases may occur.^{114 118 125 129 145 147 152 157 158 168} Modest increases not expected to have short-term sequelae; however, monitor all patients for hypertension and tachycardia.^{114 118 125 129 145 147 152 157 158 168}

Psychiatric Adverse Effects

May exacerbate symptoms of behavior disturbance and thought disorder in patients with preexisting psychotic disorder.^{114 118 125 129 145 147 152 157 158 168}

May precipitate mixed or manic episodes in ADHD patients with comorbid bipolar disorder.^{114 118 125 129 145 147 152 157 158 168} Prior to initiating therapy, carefully screen patients with ADHD to determine if they are at risk for developing a manic episode; screening should include a detailed psychiatric history (e.g., current or prior depressive symptoms; family history of suicide, bipolar disorder, or depression).^{114 118 125 129 145 147 152 157 158 168}

Psychotic or manic symptoms (e.g., hallucinations, delusional thinking, mania) also may occur with usual dosages in patients without history of psychotic illness.^{114 118 125 129 145 147 152 157 158 168} If psychotic or manic symptoms occur, consider discontinuance of therapy.^{114 118 125 129 145 147 152 157 158 168}

Seizures

Stimulant therapy may lower the seizure threshold in patients with and without prior seizures or a history of electroencephalography (EEG) abnormalities.^{118 147 152} If seizures occur during methylphenidate therapy, discontinue the drug.^{118 147 152}

Priapism

Prolonged and painful erections reported rarely in adult and pediatric patients.^{114 118 125 129 145 147 152 157 158 168} Priapism often reported during continued therapy or following an increase in dosage; also has occurred during temporary interruptions in therapy (e.g., drug holidays) or following drug discontinuance.^{114 118 125 129 145 147 152 157 158 168}

Patients who develop abnormally sustained, or painful, erections must seek immediate medical attention.^{114 118 125 129 145 147 152 157 158 168}

Peripheral Vasculopathy, including Raynaud's Phenomenon

Peripheral vascular disorders, including Raynaud’s phenomenon, reported in patients in all age groups receiving stimulants at therapeutic dosages and at various times throughout treatment course. Manifestations usually intermittent and mild, but ulceration of digits and/or breakdown of soft tissue occur rarely.^{114 118 125 129 145 147 152 157 158 168} Carefully observe for digital changes.^{114 118 125 129 145 147 152 157 158 168}

Improvement generally occurs following dosage reduction or drug discontinuance; however, some patients may require further evaluation (e.g., referral to rheumatologist).^{114 118 147 152}

Long-Term Suppression of Growth in Pediatric Patients

Long-term administration of stimulants associated with at least a temporary suppression of normal weight and/or height patterns in some pediatric patients.^{114 118 125 129 145 147 152 157 158 168}

Manufacturers recommend monitoring growth closely during treatment; patients not growing or gaining weight as expected may require temporary discontinuance of treatment.^{114 118 125 129 145 147 152 157 158 168}

Potential for Gastrointestinal Obstruction

Extended-release trilayer or bilayer core tablets generally should not be used in patients with severe preexisting GI narrowing; because these preparations are nondeformable and do not appreciably change shape in the GI tract, obstruction may occur.^{118 553}

Acute Angle Closure Glaucoma

Angle closure glaucoma reported.^{114 118 125 129 145 147 152 157 158 168} Patients at an increased risk for acute angle closure glaucoma (e.g., with significant hyperopia) should undergo ophthalmologist evaluation. ^{114 118 125 129 145 147 152 157 158 168}

Increased Intraocular Pressure and Glaucoma

Elevated IOP reported.^{114 118 125 129 145 147 152 157 158 168} Manufacturers recommend prescribing methylphenidate only when benefits outweigh risks in patients with open-angle glaucoma or abnormally increased IOP.^{114 118 125 129 145 147 152 157 158 168} Monitor for ophthalmologic changes if methylphenidate is used in patients with a history of abnormally increased IOP or open angle glaucoma.^{114 118 125 129 145 147 152 157 158 168}

Motor and Verbal Tics and Worsening of Tourette's Syndrome

Onset or exacerbation of motor or verbal tics and worsening of Tourette’s syndrome reported with CNS stimulants.^{114 118 125 129 145 147 152 157 158 168}

Prior to initiating therapy, screen patients for a family history and clinically evaluate for motor or verbal tics or Tourette’s syndrome.^{114 118 125 129 145 147 152 157 158 168} Routinely monitor patients receiving methylphenidate therapy for emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically indicated.^{114 118 125 129 145 147 152 157 158 168}

Risks in Patients with Phenylketonuria

Some oral formulations may contain aspartame, which is metabolized in the GI tract to provide phenylalanine.¹⁷¹ Each 20-, 30-, or 40-mg extended-release chewable tablet (QuilliChew ER) provides 3, 4.5, or 6 mg of phenylalanine, respectively.¹⁷¹

External Heat with the Transdermal System

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

Contact Sensitization with the Transdermal System

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

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

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

Chemical Leukoderma with the Transdermal System

Permanent depigmentation or hypopigmentation reported in patients receiving methylphenidate transdermal system.^{147 163} Usually limited to application sites, but skin color changes affecting other areas of the body also reported.^{147 163} Time to onset has ranged from 2 months to 4 years; affected areas up to 8 inches in diameter reported.¹⁶³ Can mimic appearance of vitiligo, particularly if areas distant from application site are affected; possible increased risk in individuals with history of vitiligo and/or family history of vitiligo.¹⁴⁷

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

Risk of Choking with Chewable Tablets

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

Specific Populations

Pregnancy

Available data on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, spontaneous abortion, or adverse maternal or fetal outcomes; however, there may be fetal risks associated with CNS stimulant use.^{114 118 125 129 145 147 152 157 158 168} CNS stimulants can cause vasoconstriction and thereby decrease placental perfusion.^{114 118 125 129 145 147 152 157 158 168}

No fetal and/or neonatal adverse reactions reported with therapeutic dosages of methylphenidate during pregnancy, but premature delivery and low birth-weight infants reported in amphetamine-dependent women.^{114 118 125 129 145 147 152 157 158 168}

In animal studies, increased incidence of spina bifida observed in rabbits with methylphenidate administration.^{114 118 125 129 145 147 152 157 158 168}

National Pregnancy Registry for ADHD Medications at 866-961-2388 or [Web].^{114 118 125 129 145 147 152 157 158 168}

Lactation

Limited data (case reports) suggest breast-fed infants receive 0.2–0.7% of the maternal weight-adjusted dosage of methylphenidate; milk-to-plasma ratios of 1.1–2.7 reported.^{114 118 125 129 145 147 152 157 158 168} Adverse effects on breast-fed infants or on milk production not reported to date; however, any long-term neurodevelopmental effects are unknown.^{114 118 125 129 145 147 152 157 158 168}

Consider developmental and health benefits of breast-feeding, the importance of methylphenidate to the woman, and any potential adverse effects of either the drug or the underlying maternal condition on the breast-fed infant.^{114 118 125 129 145 147 152 157 158 168}

If used in a nursing woman, monitor breast-fed infant for adverse effects (e.g., agitation, insomnia, anorexia, reduced weight gain).^{114 118 125 129 145 147 152 157 158 168}

Pediatric Use

Although safety and efficacy not established in children <6 years of age, AAP states methylphenidate may be considered for treatment of ADHD in preschool-aged children^† (4 years of age to the sixth birthday) if first-line treatments (i.e., parent training in behavior management and/or behavioral classroom interventions) do not provide substantial improvement and there is continued, moderate to severe disturbance in the child's functioning.⁵⁰⁰ Some studies suggest increased incidence of adverse effects (e.g., weight loss, increased mood lability and dysphoria ) and possibly different adverse effects in preschool-aged children.^{140 168 500 512} Systemic exposure may be increased in preschool-aged children.¹⁶⁸ Initiate at low dosage and increase in smaller increments in preschool-aged children; maximum dosages not adequately studied.⁵⁰⁰ Additional study and experience required to further elucidate safety and efficacy in this age group.⁵¹²

Long-term administration associated with at least a temporary suppression of normal weight and/or height patterns in children.^{114 118 125 129 147 152}

In toxicity studies in juvenile rats, methylphenidate associated with long-term behavioral effects (decreased spontaneous locomotor activity in adulthood, deficit in acquisition of a specific learning task in female rats).¹¹⁴ Clinical relevance unknown.¹¹⁴

Geriatric Use

Not studied in patients ≥65 years of age.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

Hepatic Impairment

Although methylphenidate has not been studied in patients with hepatic impairment,^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} hepatic impairment is expected to have minimal effects on pharmacokinetics.^{114 125 129 145 158}

Renal Impairment

Although methylphenidate has not been studied in patients with renal impairment,^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} renal impairment is expected to have minimal effects on pharmacokinetics.^{114 125 129 145 158}

Common Adverse Effects

Immediate-release conventional tablets and oral solution: Tachycardia, palpitations, headache, insomnia, anxiety, hyperhidrosis, weight loss, decreased appetite, dry mouth, nausea, and abdominal pain.^{114 145}

Immediate-release chewable tablets: Nervousness and insomnia; can be minimized with dosage reduction and omitting administration in afternoon or evening.¹⁵²

Extended-release trilayer (e.g., Concerta; generics) and bilayer (e.g., Relexxii) core tablets (>5% of children and adolescents): Abdominal pain.^{118 553} In >5% of adults: Decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight loss, irritability, and hyperhidrosis.^{118 553}

Extended-release capsules (Ritalin LA) (>5% of patients): Headache, insomnia, upper abdominal pain, decreased appetite, and anorexia.¹²⁹

CD extended-release capsules (≥5% of patients and twice the rate of placebo): Anorexia and insomnia.¹²⁵

Transdermal patch in pediatric patients 6−12 years of age (≥5% of patients and twice the rate of placebo): Decreased appetite, insomnia, nausea, vomiting, weight loss, tics, affect lability, and anorexia.¹⁴⁷ In adolescents 13−17 years of age (≥5% of patients and twice the rate of placebo): Decreased appetite, nausea, insomnia, weight loss, dizziness, abdominal pain, and anorexia.¹⁴⁷ Most also had erythema at the application site.¹⁴⁷

Extended-release capsules (Aptensio XR) in ≥5% of pediatric patients 6−17 years of age: Abdominal pain, decreased appetite, and insomnia.¹⁶⁸

Delayed- and extended-release capsules (Jornay PM) in ≥5% of pediatric patients 6−12 years of age and twice the rate of placebo: Headache, psychomotor hyperactivity, and mood swings.¹⁷⁰

Drug Interactions

Not metabolized by CYP isoenzymes; does not inhibit CYP isoenzymes at clinically relevant plasma concentrations.¹²⁵

Specific Drugs

Methylphenidate Pharmacokinetics

Absorption

Bioavailability

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

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

Extended-release tablets are absorbed more slowly but to the same extent as conventional tablets.¹⁵⁸

Peak concentration and AUC were about 20 and 11% lower, respectively, for QuilliChew ER extend-release chewable tablets (single 40-mg dose) than for immediate-release chewable tablets (two 20-mg doses given 6 hours apart).¹⁷¹

Peak concentration and AUC were about 26 and 6% higher, respectively, for Cotempla XR-ODT (single dose of two 25.9-mg extended-release orally disintegrating tablets [equivalent to 60 mg of methylphenidate hydrochloride]) than for a 60-mg extended-release capsule formulation of methylphenidate hydrochloride.¹⁷²

Relative bioavailability of Concerta extended-release trilayer and Relexxii extended-release bilayer core tablets given once daily is comparable to that of conventional tablets administered 3 times daily.^{118 553} No substantial accumulation observed with repeated once-daily dosing over dose range of 18–144 mg.^{118 553}

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

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

Peak plasma concentrations and AUC were slightly lower for methylphenidate hydrochloride CD extended-release capsules (20 mg once daily) than for conventional tablets (10 mg twice daily).¹²⁵

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

Relative bioavailability of Jornay PM delayed- and extended-release capsules administered once daily is approximately 74% that of an immediate-release formulation administered in 3 divided doses daily.¹⁷⁰

Alcohol increases the rate of drug release in vitro from many extended-release preparations; see Table 4.^{125 129 157 168 170 171 172} Results provided in Table 5 for specific strengths generally are considered representative for available strengths of the respective preparations.^{118 125 129 168 171}

For timing of peak plasma concentrations for oral formulations, see Table 5.

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

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

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

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

Duration

For duration of effects for various oral methylphenidate formulations, see Table 6.

Food

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

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

Extended-release chewable tablets (QuilliChew ER): Administration with high-fat meal increases peak concentration and AUC by about 20% and 4%, respectively, but does not affect time to peak concentration.¹⁷¹

Extended-release orally disintegrating tablets (Cotempla XR-ODT): Administration with high-fat meal decreases peak concentration by approximately 24%, increases AUC by approximately 16%, and decreases time to peak concentration by about 30 minutes (from 5 hours in fasted state to 4.5 hours in fed state).¹⁷²

Extended-release trilayer (Concerta) or bilayer (Relexxii) core tablets: High-fat meal does not alter pharmacokinetics.^{118 553}

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

Extended-release capsules (Aptensio XR): Administration with high-fat meal decreases second peak plasma concentration, increases the average peak concentration by about 28%, and increases AUC by about 19%; this formulation was administered without regard to meals in clinical trials.¹⁶⁸ Opening the capsules and sprinkling the contents on applesauce does not alter bioavailability.¹⁶⁸

Extended-release capsules (methylphenidate hydrochloride CD): Administration with high-fat meal delays first peak plasma concentration by approximately 1 hour and increases average peak plasma concentration and AUC by 30 and 17%, respectively.¹²⁵ Opening the capsules and sprinkling the contents on applesauce does not alter bioavailability.¹²⁵

Extended-release capsules (Ritalin LA): Administration with high-fat meal delays first and second peak plasma concentrations and decreases second mean peak plasma concentration by 25%.¹²⁹ Opening the capsules and sprinkling the contents on applesauce does not alter bioavailability.¹²⁹

Delayed- and extended-release capsules (Jornay PM): Administration at night with high-fat meal decreases mean peak concentration by 14% and delays peak concentration by approximately 2.5 hours, but does not alter extent of absorption.¹⁷⁰ Following administration at night, a morning meal does not affect pharmacokinetics.¹⁷⁰ Opening the capsules and sprinkling the contents on applesauce does not alter pharmacokinetics.¹⁷⁰

Special Populations

Age and body weight: Systemic exposure may be higher in children than in adults following equivalent oral dosages, but pharmacokinetic profiles generally similar following adjustment for differences in body weight.^{129 157 168 170 171 172} Systemic exposure in preschool-aged children receiving Aptensio XR extended-release capsules approximately twofold to threefold higher than in older children and adolescents receiving same dosage.¹⁶⁸

Distribution

Extent

Excreted into breast milk.¹⁶⁸

Plasma Protein Binding

About 10–33%.¹²⁹

Elimination

Metabolism

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

Elimination Route

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

Half-life

For methylphenidate elimination half-lives reported for various methylphenidate formulations, see Table 7.

Special Populations

Renal impairment: Expected to have minimal effect on pharmacokinetics since <1% of dose excreted in urine as unchanged drug and major metabolite (ritalinic acid) has little or no pharmacologic activity.¹¹⁴

Hepatic impairment: Expected to have minimal effect on pharmacokinetics since main metabolic pathway involves de-esterification by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body.¹¹⁴

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

Stability

Storage

Oral

Conventional and Immediate-release Chewable Tablets and Oral Solution

Room temperature, generally 20–25°C; conventional and chewable tablets may be exposed to 15-30°C.^{114 145 152} Protect from moisture.^{145 152}

Extended-release Tablets

20–25°C (may be exposed to 15–30°C).¹⁵⁸ Protect from moisture.¹⁵⁸

Delayed- and Extended-release Capsules

20–25°C (may be exposed to 15–30°C).¹⁷⁰ Protect from moisture.¹⁷⁰

Extended-release Capsules

Room temperature, generally 20–25°C; Ritalin LA may be exposed to 15-30°C.^{125 129 168}

Extended-release Orally Disintegrating Tablets

20–25°C (may be exposed to 15–30°C).¹⁷² Store blister packages in reusable travel case after removal from carton.¹⁷²

Extended-release Trilayer and Bilayer Core Tablets

Store trilayer tablets at 25°C and bilayer tablets from 20-25°C (may be exposed to 15–30°C).^{118 553} Protect from moisture.^{118 553}

Powder for Extended-release Suspension

25°C (may be exposed to 15–30°C).¹⁵⁷

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

Topical

Transdermal System

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

Actions

• Piperidine-derivative CNS stimulant.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Mechanism of action not fully elucidated; appears to block norepinephrine and dopamine reuptake into the presynaptic neuron and increases their release into the extraneuronal space.¹¹⁴

• Racemic mixture; the d-enantiomer is the more pharmacologically active enantiomer.¹¹⁴

Advice to Patients

• Stress importance of the patient or caregiver reading the FDA-approved patient labeling (medication guide).^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Educate patients about the risk of abuse, misuse, and addiction with methylphenidate, which can lead to overdose and death.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} Do not share methylphenidate with others and store the drug in a safe (preferably locked) location to prevent abuse.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Inform patients of the potential risks in patients with serious cardiovascular disease, including sudden death.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} Inform clinicians immediately of adverse cardiovascular effects (e.g., exertional chest pain, unexplained syncope, other symptoms suggestive of cardiac disease).^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Inform patients or caregivers that methylphenidate can increase BP and pulse rate.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Inform patients or caregivers of the potential for psychotic or manic symptoms, even in patients without a history of psychotic symptoms or mania at recommended dosages.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Inform male patients and their caregivers about the possibility of painful or prolonged penile erections (priapism) and instruct them to seek immediate medical treatment if it occurs.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Inform patients and caregivers about the risk of peripheral vascular disorders, including Raynaud's phenomenon, and the associated signs and symptoms (e.g., feelings of numbness, coolness, or pain in fingers or toes; changes in color from pale to blue to red).^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} Advise patients to report any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes and to immediately contact their clinician if any signs of unexplained wounds appear on fingers or toes; further clinical evaluation may be appropriate.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Inform patients and caregivers that methylphenidate can potentially slow growth and cause weight loss in children.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Inform patients and caregivers that increased intraocular pressure and glaucoma can occur with methylphenidate therapy.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Inform patients and caregivers that motor and verbal tics and worsening of Tourette’s syndrome can occur during treatment.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553} Instruct patients to inform their healthcare provider if there is an emergence of new tics, worsening of tics, or Tourette’s syndrome worsens.^{114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• In patients receiving conventional tablets or oral solution, administer the last daily dose of these preparations before 6 p.m.^{114 145 152}

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

• Stress importance of not crushing or chewing extended-release tablets, extended-release capsules, extended-release trilayer or bilayer core tablets, or delayed- and extended-release capsules.^{118 125 129 158 168 170 553} Capsules may be opened and the contents sprinkled on applesauce.^{125 129 168 170}

• In patients receiving extended-release capsules, delayed- and extended-release capsules, extended-release orally disintegrating tablets, or extended-release chewable tablets, stress importance of not consuming alcohol, since alcohol may result in more rapid release of the drug dose.^{125 129 168 170 171 172}

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

• In patients receiving extended-release trilayer or bilayer core tablets, presence of tablet-like substance in stool is not cause for concern.^{118 553}

• In patients receiving extended-release orally disintegrating tablets, instruct patient or caregiver on appropriate administration technique.¹⁷²

• Advise patients with phenylketonuria that QuilliChew ER extended-release chewable tablets contain aspartame.¹⁷¹

• Instruct patients and/or their caregivers regarding procedure for application and removal of the transdermal system.¹⁴⁷ Provide patient and/or caregiver with a copy of the manufacturer's instructions for use.¹⁴⁷ Stress importance of not touching the adhesive layer during application to avoid absorption of the drug; if contact occurs, wash hands immediately after application.¹⁴⁷

• Inform patients or caregivers that unused or expired Daytrana patches must be disposed of in a special manner.¹⁴⁷ If a take back program is not available, patients should remove Daytrana from its pouch, separate it from its liner, fold it in half with the adhesive sides touching, and flush it immediately down the toilet.¹⁴⁷ The pouch and liner should be placed in a container, the container closed, and then thrown out in the trash (do not flush down the toilet).¹⁴⁷

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

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

• Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products, as well as any concomitant illnesses/conditions (e.g., cardiac/cardiovascular disease, mental/psychiatric disorder, suicidal ideation or behaviors, history of substance abuse).^{114 114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Stress importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{114 114 118 125 129 145 147 152 157 158 168 170 171 172 553} Inform women about pregnancy registry for ADHD medications.^{114 114 118 125 129 145 147 152 157 158 168 170 171 172 553} Advise nursing women to monitor their infants for agitation, poor feeding, and reduced weight gain.^{114 114 118 125 129 145 147 152 157 158 168 170 171 172 553}

• Inform patients or caregivers of other important precautionary information.^{114 114 118 125 129 145 147 152 157 158 168 170 171 172 553}

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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

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

Methylphenidate hydrochloride is subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.

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

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