methylphenidate (Ritalin, Ritalin SR, Ritalin LA, Aptensio XR, Concerta, Daytrana, Metadate, Metadate CD, Metadate ER, Methylin, Quillivant XR, QuilliChew ER)

Dosing and uses of Ritalin, Concerta (methylphenidate)

• Adult
• Pediatric

 

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