methylphenidate (Ritalin, Ritalin SR, Ritalin LA, Aptensio XR, Concerta, Daytrana, Metadate, Metadate CD, Metadate ER, Methylin, Quillivant XR, QuilliChew ER)
Classes: ADHD Agents; Stimulants
Dosing and uses of Ritalin, Concerta (methylphenidate)
Adult dosage forms and strengths
tablet: Schedule II
- Ritalin
- 5mg
- 10mg
- 20mg
capsule, extended-release: Schedule II
- 10mg (Aptensio XR, Ritalin LA, Metadate CD)
- 15mg (Aptensio XR)
- 20mg (Aptensio XR, Ritalin LA, Metadate CD)
- 30mg (Aptensio XR, Ritalin LA, Metadate CD)
- 40mg (Aptensio XR, Ritalin LA, Metadate CD)
- 50mg (Aptensio XR, Metadate CD)
- 60mg (Aptensio XR, Ritalin LA, Metadate CD)
tablet, extended-release: Schedule II
- 10mg (Methylin, generics)
- 18mg (Concerta)
- 20mg (Methylin, Ritalin SR, generics)
- 27mg (Concerta)
- 36mg (Concerta)
- 54mg (Concerta)
extended-release tablet, chewable (scored): Schedule II
- QuilliChew ER
- 20mg
- 30mg
- 40mg
tablet, chewable: Schedule II
- Methylin
- 2.5mg
- 5mg
- 10mg
transdermal patch: Schedule II
- Daytrana
- 10mg
- 15mg
- 20mg
- 30mg
oral solution: Schedule II
- Methylin
- 5mg/5mL
- 10mg/5mL
Attention Deficit Hyperactivity Disorder
Metadate CD: Initial, 20 mg PO qAM before breakfast; may increase in 10- to 20-mg increments, not to exceed 60 mg/day
Ritalin LA: Initial, 20 mg PO qAM; may adjust dose in weekly 10-mg increments, not to exceed 60 mg/day (patients requiring a lower initial dose may begin with 10 mg)
Concerta: Initial, 18-36 mg PO qDay; may increase by 18-mg increments at weekly intervals; maintenance dose is 18-72 mg/day
Metadate ER, Methylin ER, and Ritalin SR: Duration of action is approximately 8 hr; may use in place of methylphenidate IR tablets when 8-hr dosage of methylphenidate ER and SR tablets corresponds to the titrated 8-hour dosage of methylphenidate IR; not to exceed 60 mg/day
Methylin, Ritalin (immediate-release tablets, chewable tablets, and oral solution): 20-30 mg/day PO divided q8-12hr, 30-45 minutes before meals; may gradually increase dose at weekly intervals; some patients may require 40-60 mg/day; in others, 10-15 mg/day may be adequate
Aptensio XR: 10 mg PO qDay in AM; may increase weekly by 10-mg increments; not to exceed 60 mg/day
QuilliChew ER (chewable extended-release tablets): 20 mg PO qAM initially; may be titrated up or down weekly in increments of 10 mg, 15 mg or 20 mg, not to exceed 60 mg/day
Narcolepsy
Methylin, Ritalin (immediate-release tablets, chewable tablets, and oral solution): 20-30 mg/day PO divided q8-12hr, 30-45 minutes before meals; some patients may require 40-60 mg/day; in others, 10-15 mg/day may be adequate
Metadate ER, Methylin ER, and Ritalin SR: Duration of action is approximately 8 hr; may use in place of methylphenidate IR tablets when 8-hr dosage of methylphenidate ER and SR tablets corresponds to the titrated 8-hr dosage of methylphenidate Ir
Pediatric dosage forms and strengths
tablet: Schedule II
- Ritalin
- 5mg
- 10mg
- 20mg
capsule, extended-release: Schedule II
- 10mg (Aptensio XR, Ritalin LA, Metadate CD)
- 15mg (Aptensio XR)
- 20mg (Aptensio XR, Ritalin LA, Metadate CD)
- 30mg (Aptensio XR, Ritalin LA, Metadate CD)
- 40mg (Aptensio XR, Ritalin LA, Metadate CD)
- 50mg (Aptensio XR, Metadate CD)
- 60mg (Aptensio XR, Ritalin LA, Metadate CD)
tablet, extended-release: Schedule II
- 10mg (Methylin, generics)
- 18mg (Concerta)
- 20mg (Methylin, Ritalin SR, generics)
- 27mg (Concerta)
- 36mg (Concerta)
- 54mg (Concerta)
extended-release tablet, chewable (scored): Schedule II
- QuilliChew ER
- 20mg
- 30mg
- 40mg
tablet, chewable: Schedule II
- Methylin
- 2.5mg
- 5mg
- 10mg
transdermal patch: Schedule II
- Daytrana
- 10mg
- 15mg
- 20mg
- 30mg
oral solution: Schedule II
- Methylin
- 5mg/5mL
- 10mg/5mL
oral suspension, extended-release: Schedule II
- Quillivant XR
- 25mg/5mL (following reconstitution)
Attention Deficit Hyperactivity Disorder
<6 years: Safety and efficacy not established
≥6 years:
Methylin, Ritalin (immediate-release tablets, chewable tablets, and oral solution): 5 mg PO BID 30-45 minutes before breakfast and lunch initially; may increase by 5-10 mg/day at weekly intervals; not to exceed 60 mg/day divided BID/TId
Metadate ER, Methylin ER, and 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 SR or ER tablet size; not to exceed 60 mg/day
Metadate CD, Ritalin LA: Initial, 20 mg PO qAM; may increase by 10 mg (Ritalin LA) or 10-20 mg (Metadate CD) qWeek to not to exceed 60 mg/day
Quillivant XR (6-12 years): 20 mg PO qAM initially; may titrate at weekly intervals by weekly 10- to 20-mg increments; not to exceed 60 mg/day
Aptensio XR: 10 mg PO qDay in AM; may increase weekly by 10-mg increments; not to exceed 60 mg/day
QuilliChew ER (chewable extended-release tablets): 20 mg PO qAM initially; may be titrated up or down weekly in increments of 10 mg, 15 mg or 20 mg, not to exceed 60 mg/day
Immediate-release weight-based dosing
- Initial: 0.3 mg/kg/dose PO before breakfast and lunch; may increase by 0.1 mg/kg/dose qWeek
- Maintenance: 0.3-1 mg/kg PO before breakfast and lunch; not to exceed 2 mg/kg/day PO divided q12hr
Concerta (methylphenidate-naïve)
- Trilayer core tablets; extended-release core with immediate release
- Initial: 18 mg PO qDay; dosage may be increased by 18 mg/day at weekly intervals
- Do not exceed 54 mg/day in children (6-12 years) and 72 mg/day in adolescents (13-17 years)
Concerta (patients taking methylphenidate)
- 18 mg PO qAM (if switching from methylphenidate 5 mg PO q8-12hr)
- 36 mg PO qAM (if switching from methylphenidate 10 mg q8-12hr)
- 54 mg PO qAM (if switching from methylphenidate 15 mg PO q8-12hr)
- 72 mg PO qAM (if switching from methylphenidate 20 mg PO q8-12hr)
Transdermal patch (Daytrana)
- Indicated for children aged 6-12 years and adolescents aged 13-17 years
- Recommended starting dose for patients new to or converting from another formulation of methylphenidate is 10 mg
- Apply patch on hip 2 hours before desired onset; remove after 9 hours; alternate application site
- Dose titration, final dosage, and wear time should be individualized according to the needs and response of the patient
- Titrate to effect for best results, following are Manufacturer's recommendations
- Week 1: 10 mg (12.5 cm² patch); releases 1.1 mg/hr
- Week 2: 15 mg (18.75 cm² patch); releases 1.6 mg/hr
- Week 3: 20 mg (25 cm² patch); releases 2.2 mg/hr
- Week 4: 30 mg (37.5 cm² patch); releases 3.3 mg/hr
Narcolepsy
<6 years
- Safety & efficacy not established
≥6 years
- Methylin, Ritalin (immediate-release tablets, chewable tablets, and oral solution): 5 mg PO q12hr; may increase by 5-10 mg/day weekly; not to exceed 60 mg/day
- Metadate ER, Methylin ER, and 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 SR or ER tablet size; not to exceed 60 mg/day
Ritalin, Concerta (methylphenidate) adverse (side) effects
Frequency not defined
Headache
Hypertension
Nausea
Nervousness
Toxic psychosis
Seizures
Tachycardia
Angina
Cardiac arrhythmia
Cerebral occlusion
Increased/decreased pulse
Cerebral arteritis
Cerebral hemorrhage
Raynaud's phenomenom
Vasculitis
Anxiety
Anger
Agitation
Irritability
Vertigo
Fatigue
Erythema multiform
Hyperhidrosis
Rash
Urticaria
Exfoliative dermatitis
Dysmenorrhea
Constipation
Xerostomia
Vomiting
Weight loss
Erectile dysfunction
Muscle tightness
Paresthesia
Blurred vision
Necrotizing vasculitis
Increased cough
Dyspnea
Sinusitis
Upper respiratory tract infection
Postmarketing reports
Musculoskeletal: Rhabdomyolysis
Somnolence
Lethargy
Warnings
Black box warnings
Chronic abuse can lead to a marked tolerance and psychological dependence, with varying degrees of abnormal behavior
Frank psychotic episodes can occur, especially with parenteral abuse
Withdrawal from abusive use may result in depression
Give cautiously to patients with a history of drug dependence or alcoholism
Potential for drug dependency; withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up
Contraindications
Hypersensitivity
Glaucoma
Family history of Tourette's syndrome, motor tics
Marked anxiety, tension, agitation
Within 2 weeks of taking MAOIs: Risk of severe hypertensive reaction
Metadate CD and Metadate Er
- Heart failure, severe hypertension, arrhythmia, hyperthyroidism, recent MI or angina concomitant use of halogenated anesthetics
Cautions
Use caution in hypertension
Stimulants used to treat ADHD are associated with serious cardiovascular events including sudden death, stroke, and MI; avoid in patients with structural cardiac abnormalities or other serious heart problems
Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud phenomenon; may improve with dose reduction or discontinuation
Difficulties with accommodation and blurring of vision have been reported with stimulant treatment
Sudden deaths, stroke, and myocardial infarction reported in patients with structural cardiac abnormalities or other serious heart problems taking stimulants at usual doses
Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation
Particular care should be taken in using stimulants to treat ADHD patients with comorbid bipolar disorder because of concern for possible induction of mixed/manic episode in such patients
Aggressive behavior or hostility is often observed in children and adolescents with ADHD; monitor for the appearance of or worsening of aggressive behavior or hostility
Monitor growth during treatment of children with stimulants; may need to interrupt therapy in patients not growing or gaining weight as expected
Stimulants may lower convulsive threshold in patients with prior history of seizure, patients with prior EEG abnormalities in absence of seizures, and very rarely, patients without a history of seizures and no prior EEG evidence of seizures; discontinue therapy in the presence of seizures
Use with caution in patients who use other sympathomimetic drugs
Amphetamines may exacerbate motor and phonic tics and Tourette’s syndrome; perform clinical evaluation for tics and Tourette’s syndrome in children and their families prior to treating with stimulant medications
Rare instances of prolonged and sometimes painful erections (priapism), sometimes requiring surgical intervention, reported with methylphenidate products; typically not reported during initiation, but often subsequent to an increase in dose; seek immediate medical attention for abnormally sustained or frequent and painful erections
Carefully supervise during withdrawaL
Possibility of tolerance, psychologic dependence, and strange behavior
Monitor blood pressure and pulse; consider benefits and risks in patients for whom increase in blood pressure or heart rate would be problem
CNS stimulants may cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychiatric illness; evaluate for bipolar disorder prior to initiating therapy
Do not use Concerta with pre-existing severe gastrointestinal narrowing conditions, including esophageal motility disorders, cystic fibrosis, history of peritonitis, small bowel disease, or chronic intestinal pseudo-obstruction, or Meckel's diverticulum
Transdermal patch
- Chemical leukoderma (permanent loss of skin pigmentation) may occur at and around application site; loss of pigmentation, in some cases, has been reported at other sites distant from the application site; patients or their caregivers should watch for new areas of lighter skin, especially under the drug patch, and immediately report these changes to their health care professional; discontinue therapy if it occurs
- Acts faster on inflamed skin
- Use of transdermal methylphenidate may lead to contact sensitization; discontinue treatment if contact sensitization is suspected; erythema is commonly seen with use of transdermal methylphenidate and is not by itself an indication of sensitization; suspect sensitization if erythema is accompanied by evidence of a more intense local reaction, like edema, papules, and vesicles and do not significantly improve within 48 hr or spreads beyond patch site
- Avoid exposing application site to direct external heat sources; heat applied after patch application, increases both the rate and extent of absorption
- Perform periodic CBC, differential, and platelet counts during prolonged therapy
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown; avoid during breastfeeding; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ritalin, Concerta (methylphenidate)
Mechanism of action
Unknown; may block reuptake of norepinephrine and dopamine into presynaptic neurons; may stimulate CNS similar to amphetamines; may stimulate cerebral cortex and subcortical structures
Absorption
Bioavailability: ~30%; large individual differences (11-52%)
Duration: 3-6 hr (IR); 3-8 hr (ER, SR); 8-12 hr (CD, LA, Concerta)
Peak plasma time: 6-8 hr (PO); 7.5-10.5 hr; (patch)
Peak plasma concentration: 3.7 ng/mL (PO); 0-114 ng/mL (patch)
Onset of action
- Immediate release: ~2hr
- Sustained-release tablet: 4-7 hr
- Extended-release tablet (Concerta): 1-2 hr
- Transdermal: ~2 hr; applied heat may expedite onset
Distribution
Protein bound: 10-33%
VD: d-Methylphenidate (2.65 L/kg); l-methylphenidate (1.80 L/kg)
Metabolism
Metabolized mostly to a-phenyl-2-piperidine acetic acid (PPAA)
Elimination
Excretion: Urine (90%), mainly as PPAA
Half-life elimination
- d-Methylphenidate: 3-4 hr
- l-Methylphenidate: 1-3 hr
Pharmacogenomics
Preliminary (and sometimes conflicting) reports have investigated whether genotypes change pharmacologic response to methylphenidate
Genes studied to determine their role in methylphenidate response include the following: SLC6A3/DAT1, DRD4, ADRA2A, and COMPt
Administration
Instructions
QuilliChew Er
- Extended-release chewable tablet
- Take once in morning
- May take with or without food
- Switching from other methylphenidate products
- If switching from other methylphenidate products, discontinue that treatment, and titrate with QuilliChew ER using the titration schedule (see Pediatric Dosing)
- Do not substitute for other methylphenidate products on an mg-per-mg basis, because of different methylphenidate base compositions and differing pharmacokinetic profiles
Methylin
- Chewable tablet: Take with at least 8 ounces (a full glass) of water or other fluid; taking without enough liquid may cause choking
- Methylin ER tablet: Swallow whole; do not crush or chew
- Take all formulations 30-45 minutes before meals
Ritalin
- Ritalin, Ritalin SR tablets: Swallow whole, do not crush or chew
- Ritalin LA capsule: Swallow whole, do not crush or chew; may open capsule and sprinkle contents on applesauce and consumed immediately
- Take all formulations 30-45 minutes before meals
Metadate
- Metadate ER: Swallow whole, do not crush or chew; administer twice daily before breakfast and lunch
- Metadate CD: Swallow whole, do not crush or chew; may open capsule and sprinkle contents on applesauce and consumed immediately; administer once daily in AM
Quillivant Xr
- Oral extended-release suspension
- Shake bottle vigorously for at least 10 seconds before measuring dose
- May take with or without food
Aptensio Xr
- May take with or without food
- Advise patients to establish a routine pattern with regard to meals
- Capsules may be swallowed whole or opened and the entire contents sprinkled onto applesauce and consume immediately
Daytrana
- Apply patch on hip 2 hr before desired onset; remove after 9 hr; alternate application site