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Methylphenidate

Pronunciation

Pronunciation

(meth il FEN i date)

Index Terms

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

Metadate CD: 40 mg

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

Metadate CD: 60 mg

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

Capsule Extended Release 24 Hour, Oral, as hydrochloride:

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

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

Generic: 20 mg, 30 mg, 40 mg

Patch, Transdermal:

Daytrana: 10 mg/9 hr (30 ea); 15 mg/9 hr (30 ea); 20 mg/9 hr (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 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, 5 mg [contains aspartame; grape flavor]

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

Generic: 2.5 mg, 5 mg, 10 mg

Tablet Chewable Extended Release, Oral, as hydrochloride:

QuilliChew ER: 20 mg, 30 mg, 40 mg [contains aspartame]

Tablet Extended Release, Oral, as hydrochloride:

Concerta: 18 mg, 27 mg, 36 mg, 54 mg

Metadate ER: 20 mg [DSC]

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

Ritalin SR: 20 mg [DSC]

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

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

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

Brand Names: U.S.

  • Aptensio XR
  • Concerta
  • Daytrana
  • Metadate CD
  • Metadate ER
  • Methylin
  • QuilliChew ER
  • Quillivant XR
  • Ritalin
  • Ritalin LA
  • Ritalin SR [DSC]

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

Immediate release chewable tablet: Methylin: A high-fat meal delayed peak time (~1 hour) and increased AUC (~20%).

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%)

Extended release capsule:

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.

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.

Extended release 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 hour, resulting in 90% of the methylphenidate being released.

Extended release suspension: Quillivant XR: A high-fat meal led to an earlier peak (~1 hour), and increased Cmax (~28%) and AUC (~19%).

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

Immediate release solution: Methylin: A high-fat meal delayed peak time (~1 hour), and increased Cmax (~13%) and AUC (~25%).

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 (90%; 80% as metabolite); Feces

Onset of Action

Onset of action (AAP 2011): Children:

Oral:

Immediate release formulations [chewable tablet, oral solution, tablet (Methylin, Ritalin)]: 20 to 60 minutes

Extended release formulations [Capsule (Metadate CD, Ritalin LA), tablets (Concerta)]: 20 to 60 minutes

Sustained release tablet (Ritalin-SR): 60 to 180 minutes

Transdermal (Daytrana): 60 minutes

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

Time to Peak

Immediate release chewable tablet: Methylin: ~1 to 2 hours

Extended release chewable tablet: QuilliChew ER: 5 hours (median)

Controlled release capsule: Biphentin [Canadian product]: Children: Initial: ~2.5 hours; Adults: Initial: ~ 2 hours

Extended release capsule:

Aptensio XR: Adults: Initial: ~2 hours; Second peak: ~8 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

Extended release suspension: Quillivant XR: Children (9 to 12 years): 4.05 hours (range: 3.98 to 6 hours); Adolescents (13 to 15 years): 2 hours (range: 1.98 to 4 hours); Adults: 4 hours (range: 1.3 to 7.3 hours)

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

Immediate release solution: Methylin: 1 to 2 hours

Immediate release tablet: Children: 1.9 hours (range: 0.3 to 4.4 hours)

Sustained release tablet: Children: 4.7 hours (range: 1.3 to 8.2 hours)

Transdermal: ~8 to 10 hours

Duration of Action

Oral (AAP 2011): Children:

Immediate release formulations [Chewable tablet, oral solution, immediate release tablet (Methylin, Ritalin)]: 3 to 5 hours

Extended release capsule (Metadate CD, Ritalin LA): 6 to 8 hours

Extended release tablet (Concerta): 12 hours

Sustained release tablet (Ritalin-SR): 2 to 6 hours

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

Half-Life Elimination

Immediate release chewable tablet: Methylin: Adults: 3 hours

Controlled release capsule: Biphentin [Canadian product]: Children: 2.4 hours; Adults: 2.1 hours

Extended release capsule:

Aptensio XR: Adults: ~5 hours

Metadate CD: Adults: 6.8 hours

Ritalin LA: Children: ~2.45 hours (range: 1.5 to 4 hours); Adults: ~3.3 hours (range: 3 to 4.2 hours)

Extended release chewable tablets: ~5.2 hours

Extended release suspension: Quillivant XR: Children ≥9 years, Adolescents, and Adults: ~5 hours

Extended release tablet: Concerta: Adolescents and Adults: ~3.5 hours

Immediate release solution: Methylin: Adults: 2.7 hours

Immediate release tablet: Children: 2.5 hours (range: 1.8 to 5.3 hours); Adults: 3.5 hours (range: 1.3 to 7.7 hours)

Sustained release tablet: Adults: 3.4 hours

Transdermal: Children and Adolescents 6 to 17 years: d-methylphenidate ~4 to 5 hours, l-methylphenidate 1.4 to 2.9 hours

Protein Binding

10% to 33%

Special Populations: Children

Extended release 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.

Extended release suspension: Quillivant XR: After a single oral dose of 60 mg plasma concentrations of methylphenidate in children (9 to 12 years old) 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: Symptomatic management of narcolepsy (except Aptensio XR, Concerta, Daytrana, Metadate CD, Ritalin LA, QuilliChew ER, Quillivant XR, and Biphentin [Canadian product]).

Use: Unlabeled

Treatment of depression in medically-ill older adults or adult patients with terminal illness and/or receiving palliative care

Contraindications

US labeling: Hypersensitivity to methylphenidate or any component of the formulation; use during or within 14 days following MAO inhibitor therapy; marked anxiety, tension, and agitation (excluding Aptensio XR, QuilliChew ER, and Quillivant XR); glaucoma (excluding Aptensio XR, QuilliChew ER, and Quillivant XR); family history or diagnosis of Tourette syndrome or tics (excluding Aptensio XR, QuilliChew ER, and Quillivant XR)

Additional contraindications: 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: Ritalin and Ritalin SR: Pheochromocytoma

Dosing: Adult

ADHD: Oral:

Immediate release (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).

Extended release (ER), sustained release (SR) products (capsules, tablets, chewable tablets, and oral suspension):

Concerta: (Adults <65 years):

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

Patients currently taking immediate release (IR) methylphenidate: Initial: Note: Dosing based on current regimen and clinical judgment; suggested dosing listed below:

- Patients taking IR methylphenidate 5 mg 2 to 3 times daily or (Canadian labeling; not in US labeling) methylphenidate SR 20 mg daily: 18 mg once every morning

- Patients taking IR methylphenidate 10 mg 2 to 3 times daily or (Canadian labeling; not in US labeling) methylphenidate SR 40 mg daily: 36 mg once every morning

- Patients taking IR methylphenidate 15 mg 2 to 3 times daily or (Canadian labeling; not in US labeling) methylphenidate SR 60 mg daily: 54 mg once every morning

- Patients taking IR methylphenidate 20 mg 2 to 3 times daily: 72 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.

Aptensio XR: Initial: 10 mg once daily; may be titrated 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 be adjusted in 10 mg increments at weekly intervals to a maximum dose of 80 mg/day.

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

Metadate ER, Ritalin-SR: May be given in place of immediate release products (duration of action ~8 hours), once the immediate release formulation daily dose is titrated and the titrated 8-hour dosage corresponds to sustained or extended release tablet size; maximum: 60 mg/day

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

QuilliChew ER: Initial: 20 mg once daily in the morning; may be adjusted in 10, 15 or 20 mg at weekly intervals; 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 be adjusted in 10 mg increments at weekly intervals; maximum: 60 mg/day

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

Narcolepsy: Oral:

Immediate release 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).

Extended and sustained release tablets (Metadate ER, Ritalin-SR): May be given in place of immediate release products (duration of action ~8 hours), once the immediate release formulation daily dose is titrated and the titrated 8-hour dosage corresponds to sustained or extended release tablet size; maximum: 60 mg/day.

Depression in medically-ill older adults or adult patients with terminal illness and/or receiving palliative care (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

ADHD:

Oral, immediate release (IR) products (tablets, chewable tablets, and solution): Children ≥6 years and Adolescents: 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).

Oral, extended release (ER), sustained release (SR) products (capsules, tablets, chewable tablets, and oral suspension):

Children ≥6 years and Adolescents <18 years: Concerta: Note: For adolescents ≥18 years, refer to adult dosing.

Patients not currently taking methylphenidate: Initial: 18 mg once daily in the morning

Patients currently taking immediate release (IR) methylphenidate: Initial: Note: Dosing based on current regimen and clinical judgment; suggested dosing listed below:

- Patients taking IR methylphenidate 5 mg 2 to 3 times daily or (Canadian labeling; not in US labeling) methylphenidate SR 20 mg daily: 18 mg once every morning

- Patients taking IR methylphenidate 10 mg 2 to 3 times daily or (Canadian labeling; not in US labeling) methylphenidate SR 40 mg daily: 36 mg once every morning

- Patients taking IR methylphenidate 15 mg 2 to 3 times daily or (Canadian labeling; not in US labeling) methylphenidate SR 60 mg daily: 54 mg once every morning

- Patients taking IR methylphenidate 20 mg 2 to 3 times daily: 72 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: 54 mg/day in children 6 to 12 years or 2 mg/kg/day (up to 72 mg/day) in adolescents <18 years

Children ≥6 years and Adolescents:

Aptensio XR: Initial: 10 mg once daily; may be titrated 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 be adjusted in 10 mg increments at weekly intervals. Maximum: 60 mg/day. Note: In some children >60 kg, a maximum dose of 1 mg/kg/day (not to exceed 80 mg/day) may be necessary; however, close monitoring for adverse events is required. Reduce dose or discontinue if adverse events arise.

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

Metadate ER, Ritalin-SR: May be given in place of immediate release products (duration of action ~8 hours), once the immediate release formulation daily dose is titrated and the titrated 8-hour dosage corresponds to sustained or extended release tablet size; maximum: 60 mg/day

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

QuilliChew ER: Initial: 20 mg once daily in the morning; may be adjusted in 10, 15 or 20 mg at weekly intervals; 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 be adjusted in 10 mg increments at weekly intervals; maximum: 60 mg/day

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

Transdermal: (Daytrana): Children ≥6 years and Adolescents <18 years: Initial: 10 mg patch once daily; remove up to 9 hours after application. Titrate based on response and tolerability; may increase to next transdermal dose no more frequently than every week. Note: Application should occur 2 hours prior to desired effect. Drug absorption may continue for a period of time after patch removal. The prescribing information recommends patients converting from another formulation of methylphenidate 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 daily; 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/day of the osmotic release preparation, or 20 mg daily of the encapsulated bead preparation (Arnold, 2007).

Narcolepsy: Oral: Children ≥6 years and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

Oral: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); undergoes extensive metabolism to a renally eliminated metabolite with little or no pharmacologic activity.

Transdermal: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

Oral: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Transdermal: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

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; Canadian product): Administer in the morning with breakfast. Swallow whole; do not crush or chew capsule. Alternatively, capsules may be opened and the contents sprinkled onto applesauce, ice cream, or yogurt, but the beads must not be crushed or chewed.

Immediate release (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.

Extended release capsule (Aptensio XR, Metadate CD, Ritalin LA): Administer in the morning with or without food. 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 or chew capsule contents.

Extended release 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.

Extended release chewable tablet (QuilliChew ER): Administer in the morning with or without food.

Extended release 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): Administer 30 to 45 minutes before a meal. 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:

Extended-release:

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

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

Controlled-release (Biphentin [Canadian product]): Store at 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:

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

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.

Extended-release 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).

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 and moisture.

Sustained-release (Ritalin-SR): Store at 25°C (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

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

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

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

H2-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 I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Methylphenidate may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

MAO 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

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

All dosage forms: Frequency not always defined.

Cardiovascular: Tachycardia (5%; children and adolescents: ≤1%, transdermal), palpitations (3%), angina pectoris, cardiac arrhythmia, cerebrovascular accident, decreased pulse, hypertension, increased pulse, myocardial infarction, necrotizing angiitis, Raynaud phenomenon

Central nervous system: Headache (adults: 2% to 22%; transdermal), insomnia (adults: 12%; children and adolescents: 3% to 5%), irritability (6% to 11%), emotional lability (children: 6% to 9%; adults: 1%), anxiety (8%), tics (oral: 2% to 7%, transdermal; children: 2%), dizziness (adolescents: 2% to 7%), depressed mood (4%), initial insomnia (≤4%), nervousness (3%), restlessness (3%), aggressive behavior (2%), agitation (2%), depression (2%), hypertonia (2%), lack of emotion (2%), vertigo (2%), confusion (1%), paresthesia (1%), sedation (1%), tension (1%), tension headache (1%), drowsiness, fatigue, Gilles de la Tourette syndrome (rare), hypervigilance, lethargy, outbursts of anger

Dermatologic: Hyperhidrosis (5%), excoriation (children: 4%), skin rash (children: 2%), alopecia, erythema multiforme, exfoliative dermatitis, urticaria

Endocrine & metabolic: Weight loss (2% to 9%), decreased libido (2%), growth suppression

Gastrointestinal: Decreased appetite (2% to ≤26%), xerostomia (14%), nausea (2% to 13%), vomiting (2% to 10%), anorexia (2% to 9%; transdermal), abdominal pain (children and adolescents: 5% to 7%), bruxism (2%), dyspepsia (2%), motion sickness (children: 2%), constipation (1%), diarrhea

Genitourinary: Erectile dysfunction

Hematologic & oncologic: Immune thrombocytopenia, leukopenia, pancytopenia, thrombocytopenia

Hepatic: Increased serum bilirubin

Hypersensitivity: Hypersensitivity reaction

Local: Application site reaction

Neuromuscular & skeletal: Tremor (3%), arthralgia, dyskinesia

Ophthalmic: Blurred vision (2%), eye pain (children: 2%), accommodation disturbance, dry eye syndrome, mydriasis

Respiratory: Nasopharyngitis (children and adolescents: 3%), cough (children and adolescents: 2%), upper respiratory tract infection (2%), oropharyngeal pain (1% to 2%), dyspnea, pharyngitis, pharyngolaryngeal pain, rhinitis, sinusitis

Miscellaneous: Fever (children and adolescents: 2%), accidental injury

<1% (Limited to important or life-threatening): Abnormal behavior, abdominal distress, anaphylaxis (transdermal), angioedema (transdermal), auditory hallucination, bradycardia, cardiac arrest, chest discomfort, decreased platelet count, decreased therapeutic response, disorientation, dyskinesia, extrasystoles, hallucination, heart murmur, hepatic failure, hot flash, hyperpyrexia, increased blood pressure, increased heart rate, increased liver enzymes, increased thirst, jitteriness, lack of effectiveness of drug, leukoderma (transdermal, chemical; FDA Safety Alert 2015), macular eruption, mania, migraine, mood changes, muscle spasm, obsessive-compulsive disorder, panic attack, peripheral vascular insufficiency, priapism, psychomotor agitation, rhabdomyolysis, seizure, sleep disorder, supraventricular tachycardia, toxic psychosis, ventricular premature contractions, visual disturbance, visual hallucination, weakness

ALERT: U.S. Boxed Warning

Abuse and dependence:

Methylphenidate has a high potential for abuse and dependence. Give methylphenidate cautiously to patients with a history of drug dependence or alcoholism.

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. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular events: CNS stimulant use has been associated with serious cardiovascular events (eg, sudden death, arrhythmia, and myocardial infarction in children and adolescents; sudden death, stroke, and myocardial infarction in adults) in patients with and without preexisting structural cardiac abnormalities or other serious heart problems (Shin 2016). These products should be avoided in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that could further increase their risk of sudden death. Patients should be carefully evaluated for cardiac disease prior to initiation of therapy. Some products are contraindicated in patients with heart failure, arrhythmias or recent MI.

• Chemical leukoderma: Transdermal system may cause a persistent loss of skin pigmentation at and around the application site, as well as at distant sites from the application site; loss of skin pigmentation may continue after discontinuation of transdermal system. May resemble vitiligo especially if loss of skin pigmentation occurs at areas distant from application site; use with caution in patients with a history and/or family history of vitiligo. Monitor for signs of skin depigmentation; immediately discontinue use if patient experiences chemical leukoderma.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• 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. Digital ulceration and/or soft tissue breakdown have been observed rarely; monitor for digital changes during therapy and seek further evaluation (eg, rheumatology) if necessary.

• Priapism: Prolonged and painful erections (priapism), sometimes requiring surgical intervention, have been reported (rarely) with methylphenidate and atomoxetine use in pediatric and adult patients. 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. 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. Avoidance of stimulants and atomoxetine may be preferred in patients with severe cases that were slow to resolve and/or required detumescence (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]: Potential for drug dependency exists; avoid abrupt discontinuation in patients who have received for prolonged periods. Use caution in patients with history of ethanol or drug abuse.

• Cardiovascular disorders: Use with caution in patients with hypertension 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 pre-existing psychosis or bipolar disorder (may induce mixed/manic episode). May exacerbate symptoms of behavior and thought disorder in psychotic patients; new-onset psychosis or mania may occur with stimulant use. Patients should be screened for bipolar disorder prior to treatment; consider discontinuation if such symptoms (eg, delusional thinking, hallucinations, mania) occur. May be associated with aggressive behavior or hostility (causal relationship not established); monitor for development or worsening of these behaviors. Suicidal ideation, attempts, and very rarely, completed suicide have been reported. 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.

• 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 (AACAP [Murphy 2013; Pliszka 2007]).

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: Appetite suppression may occur, particularly in children. Use of stimulants has been associated with weight loss and slowing of growth rate; monitor growth rate 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:

• 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 suggests 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 [Canadian product]: 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 allergic contact sensitization, characterized by intense local reactions (eg, edema, papules) that may spread beyond the patch site; sensitization may subsequently manifest systemically with other routes of methylphenidate administration; monitor closely. Avoid exposure of application site to any direct external heat sources (eg, hair dryers, heating pads, electric blankets); may increase the rate and extent of absorption and risk of overdose. Efficacy of therapy for >7 weeks has not been established.

• 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 (PKU). 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 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 Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Information related to the use of methylphenidate in pregnant women with attention-deficit/hyperactivity disorder (Bolea-Akmanac, 2013; Dideriksen, 2013) or narcolepsy (Maurovich-Horvat, 2013; Thorpy, 2013) is limited.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, dry mouth, weight loss, anxiety, lack of appetite, insomnia, or abdominal pain. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), angina, dizziness, passing out, and shortness of breath, severe skin irritation, joint pain, purple patches on skin or mouth, blurred vision, vision changes, tachycardia, bradycardia, arrhythmia, severe headache, severe nausea, vomiting, seizures, dark urine, jaundice, chills, pharyngitis, tremors, abnormal movements, sweating a lot, loss of strength and energy, extremity discoloration, burning or numbness of hands or feet, wounds on fingers or toes, change in amount of urine passed, urinary retention, muscle pain, muscle weakness, priapism, signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking), hallucinations, or behavioral changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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