Methylphenidate (Ritalin)

Today's med: Methylphenidate  (meth il FEN i date) 

(brand names: Concerta, Daytrana, Metadate CD, Metadate ER, Methylin, Quillivant XR, Ritalin, Ritalin LA, Ritalin-SR)

Drug Class: CNS Stimulant

Other Drugs in this class: Lisdexamfetamine, Dexmethylphenidate,Dextroamphetamine, 

Methamphetamine,Caffeine, Methylphenidate hydrochloride,Caffeine citrate,Butalbital/Acetaminophen/Caffeine,

Dextroamphetamine sulfate,Methamphetamine hydrochloride,Lisdexamfetamine dimesylate,

Aspirin/Caffeine, Dexmethylphenidate hydrochloride, Acetaminophen/Caffeine,Butalbital/Aspirin/Caffeine,

Acetaminophen/Aspirin/Caffeine,Ergotamine/Caffeine,Dextroamphetamine/Amphetamine,Orphenadrine/Aspirin/Caffeine,Acetaminophen/Caffeine/Pyrilamine,Acetaminophen/Caffeine/Dihydrocodeine,Acetaminophen/Aspirin/Salicylamide/Caffeine,Acetaminophen/Caffeine/Isometheptene,Dihydrocodeine/Aspirin/Caffeine,

Acetaminophen/Caffeine/Salicylic acid,Codeine anhydrous/Butalbital/Caffeine/Acetaminophen,

Codeine/Butalbital/Caffeine/Aspirin

Indications: Treatment of attention-deficit/hyperactivity disorder (ADHD); symptomatic management of narcolepsy (except Concerta®, Daytrana®, Metadate CD®, Ritalin LA®, and Quillivant™ XR)

Action: 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

Contraindications: 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's syndrome or tics. Metadate CD® and Metadate® ER: Additional contraindications: Severe hypertension, heart failure, arrhythmia, hyperthyroidism, recent MI or angina; concomitant use of halogenated anesthetics.

Adverse Effects:  Cardiovascular: Angina, cardiac arrhythmia, cerebral arteritis, cerebral hemorrhage, cerebral occlusion, cerebrovascular accidents, hyper-/hypotension, MI, murmur, palpitation, pulse increased/decreased, Raynaud’s phenomenon, tachycardia, vasculitis

Central nervous system: Motion sickness (children 2%), tic (children 2%), aggression, agitation, anger, anxiety, confusional state, depression, dizziness, drowsiness, emotional lability, fatigue, fever, headache, hypervigilance, insomnia, irritability, lethargy, nervousness, neuroleptic malignant syndrome (NMS) (rare), restlessness, stroke, tension, Tourette's syndrome (rare), toxic psychosis, tremor, vertigo

Dermatologic: Excoriation (children 4%), alopecia, erythema multiforme, exfoliative dermatitis, hyperhidrosis, rash, urticaria

Endocrine & metabolic: Dysmenorrhea, growth retardation, libido decreased

Gastrointestinal: Abdominal pain, anorexia, appetite decreased, bruxism, constipation, diarrhea, dyspepsia, nausea, vomiting, weight loss, xerostomia

Genitourinary: Erectile dysfunction

Hematologic: Anemia, leukopenia, pancytopenia, thrombocytopenia, thrombocytopenic purpura

Hepatic: Bilirubin increased, hepatic coma, liver function tests abnormal, transaminases increased

Neuromuscular & skeletal: Arthralgia, dyskinesia, muscle tightness, paresthesia

Ocular: Eye pain (children 2%), blurred vision, dry eyes, mydriasis, visual accommodation disturbance

Renal: Necrotizing vasculitis

Respiratory: Cough increased, dyspnea, pharyngitis, pharyngolaryngeal pain, rhinitis, sinusitis, upper respiratory tract infection

Miscellaneous: Accidental injury, hypersensitivity reactions

Postmarketing and/or case reports (Limited to important or life-threatening): Alkaline phosphatase increased, bradycardia, disorientation, extrasystole, hallucinations; hypersensitivity reactions (eg, angioedema, anaphylactic reactions, auricular swelling, bullous conditions, exfoliative conditions, urticaria, pruritus, rash, eruptions, exanthemas); mania, migraine, obsessive-compulsive disorder, priapism, seizure, supraventricular tachycardia, ventricular extrasystole

Concerns related to adverse effects:

• Cardiovascular events: CNS stimulant use has been associated with serious cardiovascular events (eg, sudden death in children and adolescents; sudden death, stroke, and MI in adults) in patients with pre-existing structural cardiac abnormalities or other serious heart problems. 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.

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

Disease-related concerns:

• Abuse potential: [U.S. 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.

• Hypertension: 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; observe for symptoms of aggression and/or hostility.

• 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.

Special populations:

• Pediatrics: Not labeled for use in children <6 years of age. Use of stimulants has been associated with suppression of growth in children; monitor growth rate during treatment.

Dosage form specific issues:

• Concerta®: Should not be used with pre-existing 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’s 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.

• Metadate CD®: Contains sucrose; avoid administration in fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency. 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.

• Metadate® ER: Contains lactose; avoid administration in hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. Concomitant use with halogenated anesthetics is contraindicated; may cause sudden elevations in blood pressure; if surgery is planned, do not administer Metadate® ER on the day of surgery.

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, or hostility; growth rate in children; signs of central nervous system stimulation

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).

Transdermal system: Frequency of adverse events as reported in trials of 7-week duration. Incidence of some events higher with extended use.

>10%:

Central nervous system: Headache (≤15%; long-term use in children: 28%), insomnia (6% to 13%; long-term use in children: 30%), irritability (7% to 11%)

Gastrointestinal: Appetite decreased (26%), nausea (10% to 12%)

Miscellaneous: Viral infection (long-term use in children: 28%)

1% to 10%:

Cardiovascular: Tachycardia (≤1%)

Central nervous system: Tic (7%), dizziness (adolescents 6%), emotional instability (6%)

Gastrointestinal: Vomiting (3% to 10%), weight loss (6% to 9%), abdominal pain (5% to 7%), anorexia (5%; long-term use in children: 46%)

Local: Application site reaction

Respiratory: Nasal congestion (6%) nasopharyngitis (5%)

Postmarketing and/or case reports (Limited to important or life-threatening): Allergic contact dermatitis/sensitization, anaphylaxis, angioedema, hallucinations, seizures

Standard Dosing: ADHD:

Oral, immediate release (IR) products (tablets, chewable tablets, and solution): Children ≥6 years, Adolescents, and Adults: Initial: 5 mg twice daily, before breakfast and lunch; increase by 5-10 mg daily at weekly intervals; maximum dose: 60 mg daily (in 2-3 divided doses).

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

Children ≥6 years and Adolescents <18 years: Concerta®:

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 2-3 times daily or (Canadian labeling; not in U.S. labeling) methylphenidate SR 20 mg daily: 18 mg once every morning

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

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

- Patients taking IR methylphenidate 20 mg 2-3 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 18-36 mg is desired.

Maximum dose:

U.S. labeling: 54 mg daily in children 6-12 years or 2 mg/kg/day (up to 72 mg daily) in adolescents <18 years

Canadian labeling: 54 mg daily in children and adolescents 6-18 years

Children ≥6 years, Adolescents, and Adults:

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 daily

Metadate CD®, Quillivant™ XR: Initial: 20 mg once daily; may be adjusted in 10-20 mg increments at weekly intervals; maximum: 60 mg daily

Ritalin LA®: Initial: 20 mg once daily (l0 mg once daily may be considered for some patients); may be adjusted in 10 mg increments at weekly intervals; maximum: 60 mg daily

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

Adolescent ≥18 years and Adults (<65 years): Concerta®:

Patients not currently taking methylphenidate: Initial:

U.S. labeling: 18-36 mg once every morning

Canadian labeling: 18 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 2-3 times daily or (Canadian labeling; not in U.S. labeling) methylphenidate SR 20 mg daily: 18 mg once every morning

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

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

- Patients taking IR methylphenidate 20 mg 2-3 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 18-36 mg is desired. Maximum dose: 72 mg 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, Adolescents, Adults:

Immediate release tablets and solution (Methylin®, Ritalin®): Initial: 5 mg twice daily before breakfast and lunch; increase by 5-10 mg daily at weekly intervals; maximum dose: 60 mg daily (in 2-3 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 daily.

Depression (unlabeled use): Oral: Adults: Initial: 2.5 mg every morning before 9 AM; dosage may be increased by 2.5-5 mg every 2-3 days as tolerated to a maximum of 20 mg daily; may be divided (ie, 7 AM and 12 noon), but should not be given after 12 noon; do not use sustained release product

Drug interactions: http://www.drugs.com/drug-interactions/methylphenidate.html

A total of 396 drugs (3121 brand and generic names) are known to interact withmethylphenidate.

• 14 major drug interactions (72 brand and generic names)
• 367 moderate drug interactions (2977 brand and generic names)
• 15 minor drug interactions (72 brand and generic names)

Show all medications in the database that may interact with methylphenidate.

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

METH-ylpheni-DATE with ADD