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Special Alerts
Safety Review of Medications for Attention-Deficit/Hyperactivity Disorder (ADHD)
December 2011
The U.S. Food and Drug Administration (FDA) issued updated information regarding the safety of medications for attention-deficit/hyperactivity disorder (ADHD) in adults. The communication was prompted by the results of two epidemiologic studies which failed to show an increased risk of serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), and stroke, in adults who received certain medications for ADHD.
The retrospective, population-based cohort studies involved 443,198 adults (aged 25-64 years), of which 150,359 received certain ADHD medications and were matched to 292,839 nonusers (1 user to 2 nonusers). Exposure was based on electronic pharmacy records of filled prescriptions at various study sites. Current ADHD use was a median of 0.33 years and follow-up was a median of 1.3 years per person. The results found no evidence of an increased risk of MI, SCD, or stroke associated with the use of ADHD medications. Specifically, the adjusted rate ratio (RR) of serious cardiovascular events for current use compared with nonuse was 0.83 (95% CI: 0.72-0.96) (Habel, 2011).
Previously, in November 2011, the FDA communicated safety information following results of a study in children and young adults exposed to certain ADHD medications which also failed to show an association of adverse cardiovascular events (SCD, MI, and stroke) and ADHD use in that population. That retrospective cohort study included >1 million patients (aged 2-24 years) and >2 million person-years of follow-up. When compared to patients who did not receive ADHD medications, neither current (adjusted hazard ratio: 0.75; 95% CI: 0.31-1.85) or former (adjusted hazard ratio: 1.03; 95% CI: 0.57-1.89) users of ADHD medications experienced an increased rate of serious cardiovascular events (Cooper, 2011).
ADHD medications involved in these safety reviews were atomoxetine, dexmethylphenidate, dextroamphetamine, dextroamphetamine and amphetamine, lisdexamfetamine, methamphetamine, methylphenidate, and pemoline (no longer marketed).
Product labeling should continue to be followed. In general, stimulant medications and atomoxetine should not be used in patients with serious heart problems or in patients who should avoid increased blood pressure or heart rate; monitor patients for blood pressure or heart rate changes.
For more information, please refer to the following websites:
December, 2011 (adult information): http://www.fda.gov/Drugs/DrugSafety/ucm279858.htm
November, 2011 (children and young adult information): http://www.fda.gov/Drugs/DrugSafety/ucm277770.htm
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(meth il FEN i date)
Generic Available (U.S.)
Yes: Extended release capsule, extended/sustained release tablet, immediate release tablet, oral solution
Index Terms
Controlled Substance
C-II
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Concerta®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088575.pdf
Daytrana™: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021514s009s010MedGuide.pdf
Metadate CD®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088635.pdf
Methylin® chewable tablet: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088639.pdf
Methylin® oral solution: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088640.pdf
Ritalin®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089090.pdf
Ritalin LA®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089092.pdf
Ritalin-SR®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089826.pdf
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of attention-deficit/hyperactivity disorder (ADHD); symptomatic management of narcolepsy
Use: Unlabeled
Depression (especially elderly or medically ill)
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal studies have shown teratogenic effects to the fetus. There are no adequate and well-controlled studies in pregnant women. Do not use in women of childbearing age unless the potential benefit outweighs the possible risk.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Methylphenidate excretion into breast milk has been noted in case reports. In both cases, the authors calculated the relative infant dose to be ≤0.2% of the weight adjusted maternal dose. Adverse events were not noted in either infant, however, both were older (6 months of age and 11 months of age) and exposure was limited.
Contraindications
Hypersensitivity to methylphenidate, any component of the formulation, or idiosyncratic reactions to sympathomimetic amines; 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
Warnings/Precautions
Boxed warnings:
• Abuse potential: See “Disease-related concerns” below.
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.
• Long-term use: Safety and efficacy of long-term use of methylphenidate have not yet been established.
Adverse Reactions
All dosage forms: Frequency not defined:
Cardiovascular: Angina, cardiac arrhythmia, cerebral arteritis, cerebral hemorrhage, cerebral occlusion, cerebrovascular accidents, vasculitis, hyper-/hypotension, MI, murmur, palpitation, pulse increased/decreased, Raynaud's phenomenon, tachycardia
Central nervous system: Aggression, agitation, anger, anxiety, confusional state, depression, dizziness, drowsiness, fatigue, fever, headache, hypervigilance, insomnia, irritability, lethargy, mood alterations, nervousness, neuroleptic malignant syndrome (NMS) (rare), restlessness, stroke, tension, Tourette's syndrome (rare), toxic psychosis, tremor, vertigo
Dermatologic: 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, thrombocytopenic purpura, thrombocytopenia
Hepatic: Bilirubin increased, liver function tests abnormal, hepatic coma, transaminases increased
Neuromuscular & skeletal: Arthralgia, dyskinesia, muscle tightness, paresthesia
Ocular: 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: Alkaline phosphatase increased, angina pectoris, bradycardia, chest pain, diplopia, disorientation, extrasystole, mydriasis; hypersensitivity reactions (eg, angioedema, anaphylactic reactions, auricular swelling, bullous conditions, exfoliative conditions, urticaria, pruritus, rash, eruptions, exanthemas); migraine, muscle twitching, hallucinations, mania, erythema, obsessive-compulsive disorder, seizure, supraventricular tachycardia, ventricular extrasystole
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, dyskinesia, hallucinations, seizures
Metabolism/Transport Effects
Inhibits CYP2D6 (weak)
Drug Interactions
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. Risk C: Monitor therapy
Antihypertensives: Methylphenidate may diminish the antihypertensive effect of Antihypertensives. Exceptions: Minoxidil (Topical). Risk C: Monitor therapy
Anti-Parkinson's Agents (Dopamine Agonist): Methylphenidate may enhance the adverse/toxic effect of Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy
Antipsychotics: May enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotics. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CloNIDine: Methylphenidate may enhance the adverse/toxic effect of CloNIDine. Risk C: Monitor therapy
Fosphenytoin: Methylphenidate may increase the serum concentration of Fosphenytoin. Risk C: 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. Risk C: Monitor therapy
Inhalational Anesthetics: Methylphenidate may enhance the hypertensive effect of Inhalational Anesthetics. Risk X: Avoid combination
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Ioflupane I 123: Methylphenidate may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypertensive effect of Methylphenidate. Risk X: Avoid combination
PHENobarbital: Methylphenidate may increase the serum concentration of PHENobarbital. Risk C: Monitor therapy
Phenytoin: Methylphenidate may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Primidone: Methylphenidate may increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations could become elevated. Methylphenidate may increase the serum concentration of Primidone. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tricyclic Antidepressants: Methylphenidate may enhance the adverse/toxic effect of Tricyclic Antidepressants. Methylphenidate may increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Methylphenidate may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may cause CNS depression).
Food: Food may increase oral absorption; Concerta® formulation is not affected. Food delays early peak and high-fat meals increase Cmax and AUC of Metadate CD® formulation.
Herb/Nutraceutical: Avoid ephedra (may cause hypertension or arrhythmias) and yohimbe (also has CNS stimulatory activity).
Storage
Capsule: Extended release: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
Solution: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F).
Tablet:
Chewable: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light and moisture.
Extended and sustained release: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light and moisture.
Immediate release: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light and moisture.
Osmotic controlled release (Concerta®): Store at controlled room temperature of 25°C; excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from humidity.
Transdermal system: 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.
Mechanism of 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
Pharmacodynamics/Kinetics
Onset of action: Peak effect:
Immediate release tablet: Cerebral stimulation: ~2 hours
Extended release capsule (Metadate CD®, Ritalin LA®): Biphasic; initial peak similar to immediate release product, followed by second rising portion (corresponding to extended release portion)
Sustained release tablet: 4-7 hours
Osmotic release tablet (Concerta®): Initial: 1-2 hours
Transdermal: ~2 hours; may be expedited by the application of external heat
Duration: Immediate release tablet: 3-6 hours; Sustained release tablet: 8 hours; Extended release tablet: Methylin® ER, Metadate® ER: 8 hours, Concerta®: 12 hours
Absorption:
Oral: Readily absorbed
Transdermal: Absorption increased when applied to inflamed skin or exposed to heat. Absorption is continuous for 9 hours after application.
Distribution: Vd: d-methylphenidate: 2.65 ± 1.11 L/kg, l-methylphenidate: 1.80 ± 0.91 L/kg
Protein binding: 10% to 33%
Metabolism: Hepatic via carboxylesterase CES1A1 to minimally active metabolite
Half-life elimination: d-methylphenidate: 3-4 hours; l-methylphenidate: 1-3 hours
Time to peak: Concerta®: Cmax: 6-8 hours; Daytrana™: 7.5-10.5 hours
Excretion: Urine (90% as metabolites and unchanged drug)
Dosage
ADHD:
Oral, immediate release products: Children ≥6 years and Adults: Initial: 5 mg/dose (~0.3 mg/kg/dose) given twice daily before breakfast and lunch; increase by 5-10 mg/day (0.2 mg/kg/day) at weekly intervals; maximum dose: 60 mg/day (2 mg/kg/day). Note: Discontinue periodically to re-evaluate or if no improvement occurs within 1 month.
Oral, extended release products:
Children 6-12 years and Adolescents 13-17 years: Concerta®:
Patients not currently taking methylphenidate: Initial dose: 18 mg once daily in the morning
Patients currently taking methylphenidate: Note: Initial dose: Dosing based on current regimen and clinical judgment; suggested dosing listed below:
- Patients taking methylphenidate 5 mg 2-3 times/day or methylphenidate SR 20 mg/day (Canadian labeling; not in U.S. labeling): 18 mg once every morning
- Patients taking methylphenidate 10 mg 2-3 times/day or methylphenidate SR 40 mg/day (Canadian labeling; not in U.S. labeling): 36 mg once every morning
- Patients taking methylphenidate 15 mg 2-3 times/day or methylphenidate SR 60 mg/day (Canadian labeling; not in U.S. labeling): 54 mg once every morning
- Patients taking methylphenidate 20 mg 2-3 times/day: 72 mg once every morning
Dose adjustment: May increase dose in increments of 18 mg; dose may be adjusted 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/day in children 6-12 years or 2 mg/kg/day (up to 72 mg/day) in adolescents 13-17 years
Canadian labeling: 54 mg/day in children and adolescents 6-18 years
Children ≥6 years and Adults:
Metadate® ER, Methylin® ER, Ritalin® SR: May be given in place of immediate release products, once the daily dose is titrated and the titrated 8-hour dosage corresponds to sustained or extended release tablet size; maximum: 60 mg/day
Metadate CD®, Ritalin LA®: Initial: 20 mg once daily; may be adjusted in 10-20 mg increments at weekly intervals; maximum: 60 mg/day
Adults: Concerta®:
Patients not currently taking methylphenidate: Initial dose:
U.S. labeling: 18-36 mg once every morning
Canadian labeling: 18 mg once every morning
Patients currently taking methylphenidate: Note: Initial dose: Dosing based on current regimen and clinical judgment; suggested dosing listed below:
- Patients taking methylphenidate 5 mg 2-3 times/day or methylphenidate SR 20 mg/day (Canadian labeling; not in U.S. labeling) : 18 mg once every morning
- Patients taking methylphenidate 10 mg 2-3 times/day or methylphenidate SR 40 mg/day (Canadian labeling; not in U.S. labeling): 36 mg once every morning
- Patients taking methylphenidate 15 mg 2-3 times/day or methylphenidate SR 60 mg/day (Canadian labeling; not in U.S. labeling): 54 mg once every morning
- Patients taking methylphenidate 20 mg 2-3 times/day: 72 mg once every morning
Dose adjustment: May increase dose in increments of 18 mg; dose may be adjusted 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/day.
Transdermal (Daytrana™): Children 6-12 years and Adolescents 13-17 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/day; for example, the 18.75 mg patch has been investigated to have the same effect as 22.5 mg/day of the immediate release preparation, 27 mg/day of the osmotic release preparation, or 20 mg/day of the encapsulated bead preparation (Arnold, 2010).
Narcolepsy: Oral: Adults: 10 mg 2-3 times/day, up to 60 mg/day
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/day; may be divided (ie, 7 AM and 12 noon), but should not be given after noon; do not use sustained release product
Administration: Oral
Do not crush or allow patient to chew sustained or extended release dosage form. To effectively avoid insomnia, dosing should be completed by noon.
Concerta®: Administer dose once daily in the morning. May be taken with or without food, but must be taken with water, milk, or juice.
Metadate CD®, Ritalin LA®: Capsules may be opened and the contents sprinkled onto a small amount (equal to 1 tablespoon) of cold applesauce. Swallow applesauce without chewing. Do not crush or chew capsule contents.
Methylin® chewable tablet: Administer with at least 8 ounces of water or other fluid.
Administration: 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.
Monitoring Parameters
Blood pressure, heart rate, signs and symptoms of depression, aggression, or hostility; CBC, differential and platelet counts, liver function tests; 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).
Test Interactions
May interfere with urine detection of amphetamines/methamphetamines (false-positive).
Dietary Considerations
Should be taken 30-45 minutes before meals. Concerta® is not affected by food. Some products may contain phenylalanine.
Patient Education
Response may take some time. Do not crush or chew long-acting forms. Tablets and sustained release tablets should be taken 30-45 minutes before meals. Concerta® may be taken with or without food, but must be taken with water, milk, or juice. Metadate CD® and Ritalin LA® capsules may be opened and the contents sprinkled onto a small amount (equal to 1 tablespoon) of applesauce; swallow applesauce without chewing. Transdermal: Apply to clean, dry skin, immediately after removing from package. Firmly press in place and hold for 30 seconds. Avoid exposing application site to external heat sources. Total wear time should not exceed 9 hours. Avoid alcohol and caffeine. You may experience decreased appetite or weight loss, restlessness, impaired judgment, or dizziness, especially during early therapy. Report unresolved rapid heartbeat, chest pain, difficulty breathing, and fainting; excessive agitation or nervousness; insomnia, tremors, or dizziness; or skin rash.
Geriatric Considerations
Methylphenidate is often useful in treating elderly patients who are discouraged, withdrawn, apathetic, or disinterested in their activities. In particular, it is useful in patients who are starting a rehabilitation program but have resigned themselves to fail; these patients may not have a major depressive disorder; will not improve memory or cognitive function; use with caution in patients with dementia who may have increased agitation and confusion.
Additional Information
Treatment with methylphenidate may include “drug holidays” or periodic discontinuation in order to assess the patient's requirements and to decrease tolerance and limit suppression of linear growth and weight. Specific patients may require 3 doses/day for treatment of ADHD (ie, additional dose at 4 PM).
Concerta® is an osmotic controlled release formulation (OROS®) of methylphenidate. The tablet has an immediate-release overcoat that provides an initial dose of methylphenidate within 1 hour. The overcoat covers a trilayer core. The trilayer core is composed of two layers containing the drug and excipients, and one layer of osmotic components. As water from the gastrointestinal tract enters the core, the osmotic components expand and methylphenidate is released.
Metadate CD® capsules contain a mixture of immediate release and extended release beads, designed to release 30% of the dose immediately and 70% over an extended period.
Ritalin LA® uses a combination of immediate release and enteric coated, delayed release beads.
Cardiovascular Considerations
Amphetamines should be avoided in patients with known or suspected cardiovascular disease. They may precipitate marked increases in blood pressure, tachycardia, and tachyarrhythmias. These drugs are often used recreationally and inappropriately, particularly for appetite suppressant effects. Recreational use of amphetamines should be considered in otherwise healthy patients with new onset hypertension, tachycardia, or tachyarrhythmias.
ADHD: Cardiovascular Evaluation: In an effort to reduce the rate of sudden cardiac death especially in pediatric patients receiving stimulant medications for the treatment of attention-deficit/hyperactivity disorder (ADHD), the American Heart Association (AHA) issued a statement in April 2008 (Vetter, 2008) recommending that all children diagnosed with ADHD who may be candidates for stimulant medications have a thorough cardiovascular assessment (including a combination of a thorough medical history, family history, and physical examination with the intent to identify risk factors for sudden death) prior to initiation of drug therapy. Although not mandatory, physicians should consider obtaining an ECG. These recommendations are based on the Food and Drug Administration (FDA) reports of serious cardiovascular adverse events (including sudden death) in patients (both children and adults) taking usual doses of stimulant medications. Most of these patients were found to have underlying structural heart disease (eg, hypertrophic obstructive cardiomyopathy). Stimulant medications theoretically increase cardiovascular risk due to potential effects on blood pressure elevation and increased heart rate. These effects have generally been considered clinically insignificant in most children; however, may be detrimental in certain patients with underlying cardiovascular disease. In a large retrospective cohort study involving 1,200,438 children and young adults (aged 2-24 years), none of the currently available stimulant medications or atomoxetine were shown to increase the risk of serious cardiovascular events (ie, acute MI, sudden cardiac death, or stroke) in current (adjusted hazard ratio: 0.75; 95% CI: 0.31-1.85) or former (adjusted hazard ratio: 1.03; 95% CI: 0.57-1.89) users compared to nonusers (Cooper, 2011). Results from studies involving adults (aged 25-64 years) are forthcoming.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Up to 10% of patients taking amphetamine-like drugs may present with hypertension. Monitor blood pressure prior to using local anesthetic with vasoconstrictors.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Nursing: Physical Assessment/Monitoring
Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance. Evaluate periodically for need for continued use. After long-term use, taper dosage slowly when discontinuing. In children, monitor growth pattern. If growth/weight gain is not as expected, may need to discontinue medication. Perform careful cardiovascular assessment prior to initiating therapy. Assess vital signs at beginning of therapy and periodically throughout.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, extended release, oral, as hydrochloride [bi-modal release]: 20 mg [generic for Ritalin LA®], 30 mg [generic for Ritalin LA®], 40 mg [generic for Ritalin LA®]
Metadate CD®: 10 mg [contains sucrose; 3 mg immediate release, 7 mg extended release]
Metadate CD®: 20 mg [contains sucrose; 6 mg immediate release, 14 mg extended release]
Metadate CD®: 30 mg [contains sucrose; 9 mg immediate release, 21 mg extended release]
Metadate CD®: 40 mg [contains sucrose; 12 mg immediate release, 28 mg extended release]
Metadate CD®: 50 mg [contains sucrose; 15 mg immediate release, 35 mg extended release]
Metadate CD®: 60 mg [contains sucrose; 18 mg immediate release, 42 mg extended release]
Ritalin LA®: 10 mg [5 mg immediate release, 5 mg extended release]
Ritalin LA®: 20 mg [10 mg immediate release, 10 mg extended release]
Ritalin LA®: 30 mg [15 mg immediate release, 15 mg extended release]
Ritalin LA®: 40 mg [20 mg immediate release, 20 mg extended release]
Patch, transdermal:
Daytrana®: 10 mg/9 hours (30s) [12.5 cm2, total methylphenidate 27.5 mg]
Daytrana®: 15 mg/9 hours (30s) [18.75 cm2, total methylphenidate 41.3 mg]
Daytrana®: 20 mg/9 hours (30s) [25 cm2, total methylphenidate 55 mg]
Daytrana®: 30 mg/9 hours (30s) [37.5 cm2, total methylphenidate 82.5 mg]
Solution, oral, as hydrochloride: 5 mg/5 mL (500 mL); 10 mg/mL (500 mL)
Methylin®: 5 mg/5 mL (500 mL); 10 mg/5 mL (500 mL) [grape flavor]
Tablet, oral, as hydrochloride: 5 mg, 10 mg, 20 mg
Methylin®: 5 mg [DSC]
Methylin®: 10 mg [DSC], 20 mg [DSC] [scored]
Ritalin®: 5 mg
Ritalin®: 10 mg, 20 mg [scored]
Tablet, chewable, oral, as hydrochloride:
Methylin®: 2.5 mg [contains phenylalanine 0.42 mg/tablet; grape flavor]
Methylin®: 5 mg [contains phenylalanine 0.84 mg/tablet; grape flavor]
Methylin®: 10 mg [scored; contains phenylalanine 1.68 mg/tablet; grape flavor]
Tablet, extended release, oral, as hydrochloride: 10 mg, 20 mg
Metadate® ER: 20 mg [contains lactose]
Methylin® ER: 10 mg [DSC], 20 mg [DSC]
Tablet, extended release, oral, as hydrochloride [bi-modal release]: 18 mg, 27 mg, 36 mg, 54 mg
Concerta®: 18 mg [4 mg immediate release, 14 mg extended release]
Concerta®: 27 mg [6 mg immediate release, 21 mg extended release]
Concerta®: 36 mg [8 mg immediate release, 28 mg extended release]
Concerta®: 54 mg [12 mg immediate release, 42 mg extended release]
Tablet, sustained release, oral, as hydrochloride: 20 mg
Ritalin-SR®: 20 mg [dye free]
Pricing: U.S. (www.drugstore.com)
Capsule, 24-hour (Ritalin LA)
10 mg (20): $100.99
20 mg (20): $100.99
30 mg (20): $100.99
40 mg (20): $101.98
Capsule, controlled release (Metadate CD)
10 mg (20): $98.99
20 mg (20): $98.99
30 mg (20): $98.99
60 mg (20): $162.99
Patch (Daytrana)
10 mg/9 hrs (30): $185.98
15 mg/9 hrs (30): $187.99
20 mg/9 hrs (30): $182.22
30 mg/9 hrs (30): $189.00
Tablet, controlled release (Concerta)
18 mg (20): $119.99
27 mg (20): $133.99
36 mg (20): $130.98
54 mg (20): $140.99
Tablet, controlled release (Metadate ER)
10 mg (20): $31.99
20 mg (20): $48.99
Tablet, controlled release (Methylin ER)
10 mg (20): $21.99
Tablet, controlled release (Methylphenidate HCl)
18 mg (20): $115.99
27 mg (20): $115.99
36 mg (20): $119.99
54 mg (20): $129.99
Tablet, controlled release (Methylphenidate HCl CR)
20 mg (20): $35.99
Tablet, controlled release (Ritalin SR)
20 mg (20): $59.99
Tablets (Methylin)
10 mg (20): $13.99
Tablets (Methylphenidate HCl)
5 mg (20): $29.99
10 mg (20): $22.24
20 mg (20): $20.99
Tablets (Ritalin)
5 mg (20): $41.20
10 mg (20): $29.99
20 mg (20): $42.39
References
Arnold LE, Lindsay RL, López FA, et al, "Treating Attention-Deficit/Hyperactivity Disorder With a Stimulant Transdermal Patch: The Clinical Art," Pediatrics, 2007, 120(5):1100-6.
Bond WS, “Recognition and Treatment of Attention Deficit Disorder,” Clin Pharm, 1987, 6(8):617-24.
Cooper WO, Habel LA, Sox CM, et al, “ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults,” N Engl J Med, 2011, 365(20):1896-904.
Emptage RE and Semla TP, “Depression in the Medically Ill Elderly: A Focus on Methylphenidate,” Ann Pharmacother, 1996, 30(2):151-7.
Greenhill LL, “Pharmacologic Treatment of Attention Deficit Hyperactivity Disorder,” Psychiatr Clin North Am, 1992, 15(1):1-27.
Gurian B and Rosowsky E, “Low-Dose Methylphenidate in the Very Old,” J Geriatr Psychiatry Neurol, 1990, 3(3):152-4.
Habel LA, Cooper WO, Sox CM, et al, “ADHD Medications and Risk of Serious Cardiovascular Events in Young and Middle-Aged Adults,” 2011, JAMA, 306(24):2673-83.
Hackett LP, Kristensen JH, Hale TW, et al, “Methylphenidate and Breast-Feeding,” Ann Pharmacother, 2006, 40(10):1890-1.
Katon W and Raskind M, “Treatment of Depression in the Medically Ill Elderly With Methylphenidate,” Am J Psychiatry, 1980, 137(8):963-5.
Kelly DP and Aylward GP, “Attention Deficits in School-Aged Children and Adolescents,” Pediatr Clin North Am, 1992, 39(3):487-512.
Lazarus LW, Moberg PJ, Langsley PR, et al, “Methylphenidate and Nortriptyline in the Treatment of Poststroke Depression: A Retrospective Comparison,” Arch Phys Med Rehabil, 1994, 75(4):403-6.
Manzi S, Law T, Shannon MW, et al, “Methylphenidate Produces a False-Positive Urine Amphetamine Screen,” Pediatr Emerg Care, 2002, 18(5):401.
Modi NB, Lindemulder B, and Gupta SK, “ Single- and Multiple-Dose Pharmacokinetics of an Oral Once-a-day Osmotic Controlled-release OROS (Methylphenidate HCl) Formulation,” J Clin Pharmacol, 2000, 40(4):379-88.
National Institute for Health and Clinical Excellence (NICE), National Collaborating Centre for Mental Health , “Attention Deficit Hyperactivity Disorder, The NICE Guideline on Diagnosis and Management of ADHD in Children, Young People and Adults,” National Clinical Practice Guideline Number 72, 2008:1-664. Available at www.nice.org.uk/cg072
Nissen SE, “ADHD and Cardiovascular Risk,” N Engl J Med, 2006, 354(14):1445-8.
Shaywitz SE and Shaywitz BA, “Diagnosis and Management of Attention Deficit Disorder: A Pediatric Perspective,” Pediatr Clin North Am, 1984, 31(2):429-57.
Spigset O, Brede WR, and Zahlsen K, “Excretion of Methylphenidate in Breast Milk,” Am J Psychiatry, 2007, 164(2):348.
Vetter VL, Elia J, Erickson CH, et al, “Cardiovascular Monitoring of Children and Adolescents With Heart Disease Receiving Stimulant Drugs. A Scientific Statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing,” Circulation, 2008, 117:2407-23.
Wallace AE, Kofoed LL and West AN, “Double-Blind, Placebo-Controlled Trial of Methylphenidate in Older, Depressed, Medically Ill Patients,” Am J Psychiatry, 1995, 152(6):929-31.
Weiss MD and Weiss JR, “A Guide to the Treatment of Adults With ADHD,” J Clin Psychiatry, 2004, 65(Suppl 3):27-37.
Wilens TE and Biederman J, “The Stimulants,” Psychiatr Clin North Am, 1992, 15(1):191-222.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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