Methylphenidate Hydrochloride

Pronunciation

Pronunciation: meth-il-FEN-i-date HYE-droe-KLOR-ide
Class: CNS stimulant

Trade Names

Concerta
- Tablets, extended-release 18 mg
- Tablets, extended-release 27 mg
- Tablets, extended-release 36 mg
- Tablets, extended-release 54 mg

Daytrana
- Patch, transdermal 10 mg
- Patch, transdermal 15 mg
- Patch, transdermal 20 mg
- Patch, transdermal 30 mg

Metadate CD
- Capsules, extended-release 10 mg
- Capsules, extended-release 20 mg
- Capsules, extended-release 30 mg
- Capsules, extended-release 40 mg
- Capsules, extended-release 50 mg
- Capsules, extended-release 60 mg

Metadate ER
- Tablets, extended-release 10 mg
- Tablets, extended-release 20 mg

Methylin
- Tablets 5 mg
- Tablets 10 mg
- Tablets 20 mg
- Tablets, chewable 2.5 mg
- Tablets, chewable 5 mg
- Tablets, chewable 10 mg
- Solution, oral 5 mg per 5 mL
- Solution, oral 10 mg per 5 mL

Methylin ER
- Tablets, extended-release 10 mg
- Tablets, extended-release 20 mg

Ritalin
- Tablets 5 mg
- Tablets 10 mg
- Tablets 20 mg

Ritalin LA
- Capsules, extended-release 10 mg
- Capsules, extended-release 20 mg
- Capsules, extended-release 30 mg
- Capsules, extended-release 40 mg

Ritalin-SR
- Tablets, sustained-release 20 mg

Apo-Methylphenidate (Canada)
Apo-Methylphenidate SR (Canada)
Biphentin (Canada)
PMS-Methylphenidate (Canada)

Pharmacology

Exact mechanism of action unknown, but presumably activates brain stem cell arousal system and cortex to produce its stimulant effect. Methylphenidate is thought to block reuptake of norepinephrine and dopamine into the presynaptic neuron and increase release of these monoamines into extraneuronal space.

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Pharmacokinetics

Absorption

Readily absorbed. Absolute bioavailability is approximately 30% in children. T max is about 1.9 h for immediate-release (IR) tablets, and 4.7 h for extended-release (ER) and sustained-release (SR) tablets. T max for Concerta is between 6 and 10 h. T max for chewable tablets and oral solution is approximately 1 to 2 h. Presence of food delays T max of all doseforms by 1 to 2 h.

Daytrana : Mean peak plasma level is 39 ng/mL (range, 0 to 114 ng/mL), which varies inversely by patient age (eg, 25 ng/mL in patients 12 yr of age; 53 ng/mL in patients 6 yr of age). Mean peak concentrations of d-methylphenidate are 1.9-fold higher than observed with a once-daily oral formulation over a period of 7.5 to 10.5 h. When applied to inflamed skin, both rate and extent of drug absorption are increased.

Distribution

Protein binding is low (10% to 33%); Vd is about 6 L/kg.

Metabolism

Metabolized by de-esterification to d-ritalinic acid (inactive).

Daytrana : Because the first-pass effect is decreased with transdermal administration, a lower dose on a mg/kg basis may produce higher exposure of d-methylphenidate compared with oral administration.

Elimination

Approximately 90% recovered in urine (approximately 80% as ritalinic acid). The half-life of methylphenidate from IR tablets is about 2.9 h; about 3.4 h from ER and SR tablets and capsules; 6.8 h from Metadate CD .

Daytrana : Mean elimination half-life in children 6 to 12 yr of age is approximately 3 to 4 h.

Special Populations

Renal Function Impairment

Renal function is expected to have minimal effects on the pharmacokinetics of methylphenidate because less than 1% of a radiolabeled dose is excreted in the urine as unchanged compound, and the major metabolite has little or no pharmacologic activity.

Hepatic Function Impairment

Hepatic insufficiency is expected to have minimal effect on the pharmacokinetics of methylphenidate because it is metabolized primarily by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body.

Gender

Pharmacokinetics are similar between boys and girls.

Race

Differences in pharmacokinetics have not been defined.

Indications and Usage

Treatment of attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD); narcolepsy (except Concerta , Daytrana , Metadate CD , Ritalin LA ).

Unlabeled Uses

Depression in medically ill elderly patients; alleviation of neurobehavioral symptoms after traumatic brain injury; improvement in pain control, sedation, or both in patients receiving opiates.

Contraindications

Marked anxiety, agitation, and tension; glaucoma; motor tics; family history or diagnosis of Tourette syndrome; concurrent treatment with MAOIs and within a minimum of 14 days following discontinuation of an MAOI; hypersensitivity to methylphenidate or other components of the products; severe hypertension; angina pectoris; cardiac arrhythmias; heart failure; recent MI; hyperthyroidism or thyrotoxicosis.

Dosage and Administration

IR Tablets, Chewable Tablets, and Oral Solution
Adults

PO 10 to 60 mg/day in 2 to 3 divided doses.

Children 6 yr of age and older

PO 5 mg before breakfast and lunch initially; increase by increments of 5 to 10 mg/wk (max, 60 mg/day).

ER and SR Tablets
Adults and Children older than 6 yr of age

PO May be used in place of IR tablets when the 8-h dosage of ER or SR tablets corresponds to the titrated 8-h dose of IR methylphenidate. Administer at 8-h intervals.

Concerta
Patients New to Methylphenidate Adults

PO 18 or 36 mg once daily in morning initially; may increase by 18 mg/wk (max, 72 mg/day).

Children older than 6 yr of age

PO 18 mg once daily in morning initially; may increase by 18 mg/wk (max, 54 mg once daily in children 6 to 12 yr of age; 72 mg once daily in children 13 to 17 yr of age, not to exceed 2 mg/kg/day).

Patients Currently Receiving Methylphenidate Adults and Children older than 6 yr of age

PO Start with 18 mg once daily every morning in patients receiving methylphenidate 5 mg twice daily or 3 times daily; start with 36 mg every morning in patients receiving methylphenidate 10 mg twice daily or 3 times daily; start with 54 mg every morning in patients receiving methylphenidate 15 mg twice daily or 3 times daily. Start with 72 mg every morning in patients receiving methylphenidate 20 mg twice or 3 times daily. After conversion, adjust dosages to a max of 72 mg/day once daily in the morning.

Metadate CD
Adults and Children older than 6 yr of age

PO 20 mg once daily every morning before breakfast initially; increase in 10 to 20 mg increments/wk (max, 60 mg once daily in the morning).

Ritalin LA
Patients New to Methylphenidate Adults and Children older than 6 yr of age

PO 10 or 20 mg once daily in morning before breakfast initially; increase in 10 mg increments/wk (max, 60 mg once daily in the morning).

Patients Currently Receiving Methylphenidate Adults and Children older than 6 yr of age

PO Start with 10 mg once daily every morning in patients receiving methylphenidate 5 mg twice daily; start with 20 mg once daily every morning in patients receiving methylphenidate 10 mg twice daily or 20 mg SR; start with 30 mg every morning in patients receiving methylphenidate 15 mg twice daily; start with 40 mg every morning in patients receiving methylphenidate 20 mg twice daily or 40 mg SR; start with 60 mg every morning in patients receiving 30 mg twice daily or 60 mg SR.

Transdermal System
Adults and Children 6 yr of age and older

Transdermal Dosage should be titrated to effect. The patch size may be increased weekly if the response is not maximized. The recommended dosing schedule is: Week 1: Patch size 12.5 cm 2 , which delivers 10 mg per 9 h (1.1 mg/h); Week 2: Patch size 18.75 cm 2 , which delivers 15 mg per 9 h (1.6 mg/h); Week 3: Patch size 25 cm 2 , which delivers 20 mg per 9 h (2.2 mg/h); Week 4: Patch size 37.5 cm 2 , which delivers 30 mg per 9 h (3.3 mg/h).

General Advice

  • Tablets and oral solution
  • Administer IR tablets, chewable tablets, and oral solution 30 to 45 min before meals. Administer with food if GI upset occurs.
  • Administer chewable tablets with at least 240 mL (8 oz) of water or other fluid to prevent choking.
  • Measure and administer prescribed dose of oral solution using dosing syringe, dosing spoon, or dosing cup.
  • Administer ER and SR tablets without regard to meals. Administer with food if GI upset occurs.
  • Swallow ER and SR tablets whole with the aid of liquids (eg, water, juice). Do not crush, chew, or split ER or SR tablets.
  • Capsules
  • Administer ER capsules once daily in the morning before breakfast.
  • For patients having difficulty swallowing ER capsules, capsules may be carefully opened and beads sprinkled over a spoonful of cool or cold applesauce. The mixture should be consumed immediately without chewing. Fluids (eg, water) should follow intake of applesauce mixture. Do not prepare the drug and applesauce mixture ahead of time and store for future use.
  • Transdermal Patch
  • Apply patch to hip area 2 h before an effect is needed. Remove patch 9 h after application.
  • Apply transdermal patch to a clean, dry area of hip that is not oily, damaged, or irritated.
  • Avoid applying transdermal patch to the waistline because clothing may cause patch to rub off.
  • If possible, do not apply transdermal patch to same hip on consecutive days.
  • Apply transdermal patch immediately after opening pouch and removing protective lining.
  • Press transdermal patch firmly in place with the palm of the hand for approximately 30 sec.
  • After proper application, bathing, swimming, or showering should not affect transdermal patch adherence.
  • If transdermal patch falls off, a new patch may be applied at a different site, but total recommended wear time for the day should remain at 9 h.

Storage/Stability

Store Concerta and Metadate ER at 59° to 86°F. Protect from moisture. Store Daytrana transdermal system at 59° to 86°F. Do not store patches outside the pouch. Do not store patches in refrigerator or freezer. Store Methylin chewable tablets at 68° to 77°F. Protect from moisture. Store Methylin tablets and Methylin ER tablets at 68° to 77°F. Protect from light. Protect form moisture. Store Methylin oral solution at 68° to 77°F. Store Ritalin LA capsules at 59° to 86°F. Store Metadate CD and Ritalin-SR at 59° to 86°F. Protect from light. Protect from moisture. Store Ritalin tablets at 59° to 86°F. Protect from light.

Drug Interactions

Alcohol

Methylphenidate plasma concentrations may be elevated, increasing the risk of adverse reactions, including abuse liability.

Antacids/Acid suppressant ( Ritalin LA only)

Coadministration could alter the release of methylphenidate.

Anticonvulsants (eg, phenobarbital, phenytoin, primidone), coumarin anticoagulants (eg, warfarin), SSRIs (eg, fluoxetine), tricyclic antidepressants (eg, imipramine)

Plasma levels of these agents may be increased by methylphenidate, increasing the risk of adverse reactions.

Antihypertensive agents (eg, guanethidine)

The antihypertensive effects of guanethidine and other antihypertensives may be decreased.

Clonidine

Risk of serious adverse reactions may be increased.

Food

High-fat meals may delay the T max and increase the AUC of orally administered methylphenidate.

MAOIs (eg, phenelzine)

Because of the risk of hypertensive crisis, methylphenidate is contraindicated in patients receiving MAOIs and for a minimum of 14 days after discontinuation of an MAOI.

Vasopressor agents (eg, phenylephrine)

Risk of adverse effects may be increased, including hypertension and excessive stimulation.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Cardiac arrhythmias; cerebral arteritis and/or occlusion; changes in pulse and BP; tachycardia (5%); palpitations (3%); angina pectoris, bradycardia, cardiac arrest, extrasystoles, Raynaud phenomenon, supraventricular tachycardia, ventricular extrasystoles (postmarketing).

CNS

Headache (22%); insomnia (12%); anxiety (8%); dizziness (7%); irritability (6%); depressed mood (4%); nervousness, restlessness, tremor (3%); aggression, agitation, decreased libido, depression, teeth grinding, vertigo (2%); affect lability, confusional state, paresthesia, sedation, tension, tension headache (1%); drowsiness; dyskinesia; NMS; toxic psychosis; abnormal behavior, auditory hallucinations, convulsions, disorientation, dyskinesia, grand mal convulsions, hallucinations, hyperactivity, mania, reversible ischemic neurologic deficit, suicidal behavior including suicide, visual hallucinations (postmarketing).

Transdermal

Insomnia (30%); headache (28%); tic (7%); affect lability (6%).

Dermatologic

Alopecia, erythema, erythema multiforme, exfoliative dermatitis, fixed drug eruption, itching, purpura, rash, urticaria; bullous conditions, eruptions, exanthemas, pruritus (postmarketing).

Transdermal

Erythema.

EENT

Nasopharyngitis (3%); pharyngolaryngeal pain (2%); diplopia, mydriasis, visual disturbances (postmarketing).

Transdermal

Nasal congestion (6%); nasopharyngitis (5%).

GI

Dry mouth (14%); nausea (13%); upper abdominal pain (6%); vomiting (3%); dyspepsia (2%); constipation (1%); abdominal pain.

Transdermal

Nausea (12%); vomiting (10%).

Hematologic-Lymphatic

Anemia and/or leukopenia; pancytopenia, thrombocytopenia, thrombocytopenic purpura (postmarketing).

Hepatic

Abnormal liver function.

Hypersensitivity

Hypersensitivity reactions including anaphylactic reactions, angioedema, auricular swelling, bullous conditions, exfoliative conditions (postmarketing).

Lab Tests

Abnormal WBC count, decreased platelet count, increased bilirubin, increased blood alkaline phosphatase, increased hepatic enzymes (postmarketing).

Metabolic-Nutritional

Decreased appetite (25%); decreased weight (7%); anorexia (2%).

Transdermal

Anorexia (46%); decreased appetite (26%).

Musculoskeletal

Muscle tightness (2%); arthralgia, muscle twitching, myalgia (postmarketing).

Respiratory

Cough, upper respiratory tract infection (2%).

Miscellaneous

Hyperhidrosis (5%); fever (3%); hyperpyrexia (2%); Tourette syndrome; chest discomfort, chest pain, decreased drug effects, decreased therapeutic response, peripheral coldness, sudden death (postmarketing).

Transdermal

Viral infection (28%).

Precautions

Warnings

Use with caution in emotionally unstable patients, such as those with a history of alcoholism or drug dependence, because such patients may increase dosage on their own initiative. Chronically abusive use can lead to marked tolerance and psychic dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral use. Careful supervision is needed during drug withdrawal because severe depression and the effects of chronic over activity can be unmasked. Long-term follow-up may be needed because of the patient's basic personality disturbances.


Monitor

Monitor CBC, differential, and platelet counts periodically during prolonged therapy. Monitor BP in all patients taking methylphenidate. Monitor growth and weight during long-term therapy. Monitor for appearance of hostility or aggressive behavior at the beginning of therapy.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 6 yr of age.

Aggression

Aggressive behavior or hostility has been observed in children and adolescents with ADHD in postmarketing experience of some drugs used to treat ADHD.

Bipolar illness

Use with caution in patients with concurrent bipolar illness because of possible induction of a mixed/manic episode.

Contact sensitization

Use of transdermal system may lead to contact sensitization and should be discontinued if sensitization is suspected.

Dose reduction/discontinuation

Reduce dose, or discontinue therapy if necessary, if paradoxical aggravation of symptoms or other adverse reactions occur. If improvement in ADD, ADHD, or narcolepsy symptoms is not observed after appropriate dosage adjustment over a 1-mo period, discontinue the drug. Use of transdermal patch may lead to contact sensitization; discontinue if sensitization occurs. Drug treatment need not be indefinite and usually may be discontinued after puberty.

Emergence of psychotic or manic symptoms

Treatment-emergent psychotic or manic symptoms in children or adolescents without a prior history of such conditions can be caused by stimulants.

GI obstruction

Because the Concerta tablet is nondeformable and does not change shape in the GI tract, do not administer to patients with preexisting, severe GI narrowing.

Growth suppression

Has been reported with long-term use of stimulants in children. Consider interrupting treatment in patient who is not growing or gaining weight as expected.

Hypertension/CV disease

Use drug with caution.

Maintenance/Extended treatment

Periodically evaluate long-term usefulness with periods off medication to assess patient's functioning without pharmacotherapy.

Phenylketonuria

Chewable tablets contain phenylalanine: 0.42 mg in 2.5 mg tablet; 0.84 mg in 5 mg tablet; 1.68 mg in 10 mg tablet.

Psychosis

May exacerbate symptoms of behavior disturbance and thought disorders.

Seizures

May lower convulsive threshold and induce seizure activity in patients with history of seizures, prior electroencephalogram (EEG) abnormalities in absence of seizures, and, very rarely, in the absence of history of seizures and no prior EEG abnormalities. Discontinue therapy if seizures occur.

Sudden death

Sudden death has occurred in association with CNS-stimulant treatment at usual doses in children with structural cardiac abnormalities.

Visual disturbances

Blurring of vision and difficulties with accommodation may occur.

Overdosage

Symptoms

Agitation, cardiac arrhythmias, coma, confusion, convulsions, delirium, dry mucous membranes, euphoria, flushing, hallucinations, headache, hyperpyrexia, hyperreflexia, hypertension, muscle twitching, mydriasis, palpitations, sweating, tachycardia, tremors, vomiting.

Patient Information

  • Advise patient or caregiver to read patient information leaflet provided with medication before starting therapy and with each refill.
  • Advise patient or caregiver that this drug is part of a total treatment program for ADD or ADHD that should also include psychological, educational, and social interventions.
  • Advise patient or caregiver to notify school or day care personnel about medication use and administration.
  • Advise patient or caregiver that health care provider may periodically change the dose to obtain maximal benefit, and to take as prescribed and not to stop taking or change the dose unless advised by health care provider.
  • Advise patient or caregiver that health care provider may periodically discontinue medication to assess behavior and determine need to continue therapy.
  • Caution patient that drug may cause dizziness or drowsiness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patient or caregiver to notify health care provider if vision changes, appetite loss, nervousness, or difficulty sleeping occur and are bothersome, or if any unusual or unexplained symptoms or feelings are noted.
  • IR Tablets
  • Advise patient or caregiver that tablets should be taken 30 to 45 min before meals, but to take with food if stomach upset occurs.
  • Advise patient or caregiver that last dose should be taken before 6 PM to avoid sleeplessness.
  • ER Tablets
  • Advise patient or caregiver that prescribed dose should be taken once daily in the morning with the aid of liquids.
  • Caution patient or caregiver that tablets must be swallowed whole and not to crush, chew, or split the tablets.
  • Advise patient or caregiver that the tablet shell passes through the intestine and is not absorbed and may appear in their stool. Inform patient that this is normal and not to be concerned.
  • ER Capsules
  • Advise patient or caregiver that prescribed dose should be taken once daily in the morning before breakfast with the aid of liquids.
  • Caution patient or caregiver that capsules should be swallowed whole and not crushed or chewed, and the contents should not be divided.
  • If patient has difficulty swallowing capsules, advise patient or caregiver that capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The mixture should be consumed immediately without chewing and then followed by fluids (eg, water). Caution patient or caregiver not to prepare drug and applesauce mixture ahead of time and store for future use.
  • Chewable Tablet
  • Advise patient or caregiver that chewable tablets should be taken 30 to 45 min before a meal with a full glass (8 oz) of water to help prevent choking.
  • Instruct patient to immediately seek medical attention if experiencing any of the following after taking the chewable tablet: chest pain, vomiting, or difficulty swallowing or breathing.
  • Advise patient with phenylketonuria that the chewable tablet contains phenylalanine.
  • Oral Solution
  • Advise patient or caregiver that oral solution should be taken 30 to 45 min before a meal.
  • Advise patient or caregiver to measure and administer prescribed dose of oral solution using a dosing syringe, dosing spoon, or dosing cup.
  • Transdermal Patch
  • Advise patient to avoid exposing patch application site to direct external heat sources (eg, heating pads, electric blankets) while wearing the patch.
  • Advise patient to cleanse the patch area after removal to remove any remaining adhesive.
  • Encourage parent or caregiver to use administration chart included with each carton of transdermal patches to monitor application and removal times, and method of disposal.
  • Advise patient that if appetite loss or insomnia occur, to try removing the patch at an earlier time before decreasing the patch size.
  • Advise patients and caregivers to avoid touching adhesive during application, and to immediately wash hands if adhesive is touched.
  • Advise patient to use only intact patches and not to cut the patches.
  • Advise patient or caregiver to fold patch over onto itself upon removal and to flush down the toilet or to dispose of in an appropriate lidded container.

Copyright © 2009 Wolters Kluwer Health.

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