Dexmethylphenidate Hydrochloride

Pronunciation

Class: Respiratory and CNS Stimulants
VA Class: CN802
Brands: Focalin

Warning(s)

Special Alerts:

[Posted 12/17/2013] ISSUE: FDA is warning that methylphenidate products, one type of stimulant drug used to treat attention deficit hyperactivity disorder (ADHD), may in rare instances cause prolonged and sometimes painful erections known as priapism. Based on a recent review of methylphenidate products, FDA updated drug labels and patient Medication Guides to include information about the rare but serious risk of priapism. If not treated right away, priapism can lead to permanent damage to the penis.

Priapism can occur in males of any age and happens when blood in the penis becomes trapped, leading to an abnormally long-lasting and sometimes painful erection. Another ADHD drug, Strattera (atomoxetine), has also been associated with priapism in children, teens, and adults.

Priapism appears to be more common in patients taking atomoxetine than in those taking methylphenidate products; however, because of limitations in available information, FDA does not know how often priapism occurs in patients taking either type of product.

See the FDA Drug Safety Communication for additional information, including a Data Summary

BACKGROUND: Methylphenidate products are central nervous system (CNS) stimulants used to treat attention deficit hyperactivity disorder (ADHD).

RECOMMENDATION: Healthcare professionals should talk to male patients and their caregivers to make sure they know the signs and symptoms of priapism and stress the need for immediate medical treatment should it occur. Younger males, especially those who have not yet reached puberty, may not recognize the problem or may be embarrassed to tell anyone if it occurs.

Encourage your patients to read the Medication Guide they receive with every filled prescription. Use caution when considering switching patients from methylphenidate to atomoxetine. Patients should not stop taking a methylphenidate product without first discussing it with your health care professional.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.

For more information visit the FDA website at: and .

Introduction

Stimulant; the more pharmacologically active (d-threo) enantiomer of racemic methylphenidate; pharmacologic actions qualitatively similar to those of amphetamines.1 4

Uses for Dexmethylphenidate Hydrochloride

Attention Deficit Hyperactivity Disorder (ADHD)

Treatment of ADHD, alone or combined with behavioral treatment, as an adjunct to psychological, educational, social, and other remedial measures in carefully selected children ≥6 years of age, adolescents, and adults.1 4

Slideshow: Does Your Child Have ADHD? Recognizing Signs & Treatment Options

Dexmethylphenidate Hydrochloride Dosage and Administration

General

  • Carefully adjust dosage according to individual requirements and response.1 4

  • For patients whose symptoms are not severe outside school, may attempt drug holidays for all or part of the summer to assess continuing efficacy and need for therapy, as well as to minimize adverse effects.5

  • Discontinue therapy if a beneficial effect is not attained after appropriate dosage adjustment over 1 month.1 4

  • If paradoxical aggravation of symptoms occurs, reduce dosage or discontinue the drug.1 4

  • Periodically discontinue therapy to assess the patient’s condition; improvement may be maintained temporarily or permanently after the drug is discontinued.1 4

Administration

Oral Administration

Conventional Tablets

Administer orally twice daily without regard to meals; administer doses at least 4 hours apart.1

Extended-release Capsules

Administer orally once daily in the morning with or without food.4 6

Swallow capsules intact.4 6 Do not crush, chew, or subdivide the capsule contents.4 6

Alternatively, open capsule(s) and sprinkle entire contents on a small amount (e.g., 1 spoonful) of applesauce immediately prior to administration.4 6 Do not store the sprinkle/applesauce mixture for later use.4 6

Dosage

Available as dexmethylphenidate hydrochloride; dosage expressed in terms of the salt.1

Pediatric Patients

ADHD
Conventional Tablets
Oral

Children ≥6 years of age: Initially, 2.5 mg twice daily for children who currently are not receiving racemic methylphenidate or are receiving stimulants other than methylphenidate.1 Increase dosage by 2.5–5 mg daily at weekly intervals (up to maximum dosage of 20 mg daily).1

Children ≥6 years of age: Initially administer one-half the current methylphenidate hydrochloride dosage in children who are being transferred from racemic methylphenidate to dexmethylphenidate therapy.1

Extended-release Capsules
Oral

Children ≥6 years of age: Initially, 5 mg once daily for children who currently are not receiving dexmethylphenidate or racemic methylphenidate or who are receiving stimulants other than methylphenidate.4 Increase dosage by 5 mg daily at weekly intervals (up to maximum dosage of 20 mg daily).4

Children ≥6 years of age: Substitute extended-release capsules for conventional tablets at same total daily dosage.4

Children ≥6 years of age: Initially administer one-half the current methylphenidate hydrochloride dosage in children who are being transferred from racemic methylphenidate to dexmethylphenidate therapy.4

Adults

ADHD
Extended-release Capsules
Oral

Initially, 10 mg once daily for patients who currently are not receiving dexmethylphenidate or racemic methylphenidate or who are receiving stimulants other than methylphenidate.4 Increase dosage by 10 mg daily after 1 week (up to maximum dosage of 20 mg daily).4

Substitute extended-release capsules for conventional tablets at same total daily dosage.4

Initially administer one-half the current methylphenidate hydrochloride dosage in patients who are being transferred from racemic methylphenidate to dexmethylphenidate therapy.4

Prescribing Limits

Pediatric Patients

ADHD
Oral

Maximum 20 mg daily.1 4

Long-term use (>6 weeks for conventional tablets or >7 weeks for extended-release capsules) has not been studied systematically.1 4 If used for long-term therapy, periodically reevaluate the usefulness of the drug.1 4

Adults

ADHD
Oral

Maximum 20 mg daily.1 4

Long-term use (>6 weeks for conventional tablets or >7 weeks for extended-release capsules) has not been studied systematically.1 4 If used for long-term therapy, periodically reevaluate the usefulness of the drug.1 4

Special Populations

Hepatic Impairment

No specific dosage recommendations.1 4 (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage recommendations.1 4 (See Renal Impairment under Cautions.)

Cautions for Dexmethylphenidate Hydrochloride

Contraindications

  • Marked anxiety, tension, and agitation.1 4

  • Glaucoma.1 4

  • Motor tics or a family history or a diagnosis of Tourette’s syndrome.1 3 4 However, the AAP states that the presence of tics before or during medical management of ADHD is not an absolute contraindication to stimulant drug use.3

  • Concomitant or recent (within 14 days) administration of MAO inhibitors.1 4 (See MAO Inhibitors under Interactions.)

  • Known hypersensitivity to dexmethylphenidate, methylphenidate, or any ingredient in the formulation.1 4

Warnings/Precautions

Warnings

Dexmethylphenidate shares the toxic potentials of racemic methylphenidate; observe the usual precautions of racemic methylphenidate therapy.1 4

Abuse Potential

Tolerance and psychological dependence may occur with chronic abuse.1 4

Psychotic episodes can occur, particularly with parenteral abuse.1 4

Use with caution in patients with a history of drug or alcohol dependence.1 4 5 Caution may be indicated in patients with comorbid conduct disorder or a chaotic family.5 If the risk of drug abuse by the patient or the patient’s peers or family is considered high, a nonstimulant drug may be preferable.5

Withdrawal Effects

Abrupt withdrawal of therapy following prolonged administration may unmask severe depression.1 4 Long-term follow-up may be required.1 4

Sudden Death and Serious Cardiovascular Events

Sudden unexplained death, stroke, and MI reported in adults with ADHD receiving usual dosages of stimulants; sudden death also reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of the drugs.1 4

Epidemiologic data suggest a possible association between use of stimulants and sudden unexplained death in healthy children and adolescents.8 9 10 FDA unable to conclude that these data affect evaluation of overall risk and benefit of stimulants used to treat ADHD in children and adolescents.8 FDA is conducting an ongoing safety review of amphetamines and other stimulants to evaluate possible link between use of these agents and sudden death in children.8 9 10 Pediatric patients with ADHD and their parents should avoid discontinuing the child’s use of such stimulants before consulting a clinician.8

Thoroughly review medical history (including evaluation for family history of sudden death or ventricular arrhythmia) and perform physical examination in all children, adolescents, and adults being considered for stimulant therapy; if initial findings suggest presence of cardiac disease, perform further cardiac evaluation (e.g., ECG, echocardiogram).1 4

In general, avoid use of CNS stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, CAD, or other serious cardiac conditions.1 4

Patients who develop exertional chest pain, unexplained syncope, or other manifestations suggestive of cardiac disease during stimulant therapy should undergo prompt cardiac evaluation.1 4

Effects on BP and Heart Rate

Possible modest increases in average BP (i.e., by about 2–4 mm Hg) and heart rate (i.e., by about 3–6 bpm); larger increases may occur.1 4 Modest increases not expected to have short-term sequelae; however, monitor all patients for larger changes in BP and heart rate.1 4

Caution advised in patients with underlying medical conditions that might be affected by increases in BP or heart rate (e.g., hypertension, heart failure, recent MI, ventricular arrhythmia).1 4

Exacerbation or Precipitation of Psychotic Symptoms

May exacerbate symptoms of behavior disturbance and thought disorder in patients with preexisting psychotic disorder.1 4

Psychotic symptoms (e.g., hallucinations, delusional thinking) may occur with usual dosages in children and adolescents without prior history of psychotic illness.1 4 If psychotic symptoms occur, consider causal relationship to stimulants, and discontinue therapy as appropriate.1 4

Precipitation of Manic Symptoms

May precipitate mixed or manic episodes in ADHD patients with comorbid bipolar disorder; use with caution in these patients.1 4 Prior to initiating therapy, carefully screen patients with ADHD and comorbid depressive symptoms to identify risk for bipolar disorder; screening should include a detailed psychiatric history (e.g., family history of suicide, bipolar disorder, or depression).1 4

Manic symptoms may occur with usual dosages in children and adolescents without prior history of mania.1 4 If manic symptoms occur, consider causal relationship to stimulants, and discontinue therapy as appropriate.1 4

Aggression

Aggressive behavior and hostility (frequently observed in children and adolescents with ADHD) reported in patients receiving drug therapy for ADHD.1 4 No systematic evidence that stimulants cause these adverse effects; however, monitor patients beginning treatment for ADHD for onset or worsening of aggressive behavior or hostility.1 4

Growth Suppression

Long-term (i.e., >14 months) administration expected to cause at least a temporary suppression of normal weight and/or height patterns in some children and adolescents.1 4

Manufacturer recommends monitoring growth during treatment; patients not growing or gaining weight as expected may require temporary discontinuance of treatment.1 4 However, AAP states that studies of stimulants in children found little or no decrease in expected height, with any decrease in growth early in treatment being compensated for later on.3

Seizures

Possible lowering of seizure threshold in patients with history of seizures, in those with prior EEG abnormalities but no history of seizures, and, very rarely, in those without history of seizures and with no prior evidence of EEG abnormalities.1 4 If seizures occur, discontinue therapy.1 4

Visual Disturbances

Visual disturbances (difficulty with accommodation, blurred vision) reported with stimulants.1 4

General Precautions

Hematologic Monitoring

Manufacturer recommends periodic monitoring of CBC (with differential) and platelet counts during prolonged therapy;1 4 however, AAP and many clinicians consider routine hematologic monitoring unnecessary in patients receiving recommended stimulants (e.g., methylphenidate, amphetamines) in the absence of clinical signs (e.g., fever, sore throat, unusual bleeding or bruising) suggestive of hematologic toxicity.3

Specific Populations

Pregnancy

Category C.1 4

Lactation

Not known whether dexmethylphenidate is distributed into milk; caution advised if used in nursing women.1 4

Pediatric Use

Safety and efficacy not established in children <6 years of age.1 4

Aggressive behavior, hostility, and psychotic (e.g., hallucinations, delusional thinking) or manic symptoms reported in children and adolescents receiving stimulants for management of ADHD.1 4 (See Warnings under Cautions.)

Sudden death reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of stimulants.1 4 Epidemiologic data also suggest a possible association between use of stimulants and sudden death in healthy children and adolescents.8 9 10 (See Sudden Death and Serious Cardiovascular Events under Cautions.)

Long-term administration expected to cause at least a temporary suppression of normal weight and/or height patterns in some children and adolescents.1 4 (See Growth Suppression under Cautions.)

Hepatic Impairment

Safety and efficacy not established.1 4

Renal Impairment

Safety and efficacy not established.1 4

Common Adverse Effects

Conventional tablets: Abdominal pain, fever, anorexia, nausea.1

Extended-release capsules: Decreased appetite, headache, dyspepsia, dry mouth, anxiety, pharyngolaryngeal pain.4

Interactions for Dexmethylphenidate Hydrochloride

Does not inhibit CYP isoenzymes in vitro.1 4

MAO Inhibitors

Pharmacologic interaction (potentiation of pressor effects, possible hypertensive crisis); dexmethylphenidate is contraindicated in patients currently or recently (i.e., within 14 days) receiving MAO inhibitors.1 4

Pressor Agents

Possible pharmacologic interaction (increased hypertensive effects); use with caution.1 4

Drugs Affecting GI pH

Studies to evaluate the effects of changes in gastric pH on absorption of dexmethylphenidate hydrochloride extended-release capsules have not been performed.4 However, potential exists for pharmacokinetic interaction (altered release of dexmethylphenidate hydrochloride) between Focalin XR extended-release capsules and drugs that alter gastric pH (e.g., antacids, acid suppressants).4

Interactions Involving Methylphenidate

The possibility that drug interactions reported with racemic methylphenidate also could occur with dexmethylphenidate should be considered.1 4

Drug

Interaction with Methylphenidate

Comments

Anticonvulsants (e.g., phenobarbital, phenytoin, primidone)

Possible inhibition of anticonvulsant metabolism1 4

Monitor plasma anticonvulsant concentrations when initiating or discontinuing methylphenidate; reduction of anticonvulsant dosage may be required during concomitant therapy1 4

Clonidine

Serious adverse effects reported; causality not established1 4

Coumarin anticoagulants (e.g., warfarin)

Possible inhibition of anticoagulant metabolism1 4

Monitor PT when initiating or discontinuing methylphenidate; reduction of anticoagulant dosage may be required during concomitant therapy1 4

Hypotensive agents

Antagonism of hypotensive effect1 4

Serotonin-reuptake inhibitors

Possible inhibition of antidepressant metabolism1

Reduction of antidepressant dosage may be required during concomitant therapy1

Tricyclic antidepressants (e.g., clomipramine, desipramine, imipramine)

Possible inhibition of antidepressant metabolism1 4

Reduction of antidepressant dosage may be required during concomitant therapy1 4

Dexmethylphenidate Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Readily absorbed following oral administration.1 Mean absolute bioavailability is 22–25% due to high first-pass metabolism.4

Peak plasma concentrations for conventional tablets are achieved within 60–90 minutes following oral administration in fasting patients.1

Peak plasma concentrations for extended-release capsules (Focalin XR) are attained at 1.5 hours and again at 6.5 hours after a dose.4

Extended-release capsules are absorbed more slowly but to the same extent as conventional tablets.4 AUC is similar for extended-release capsules (administered once daily) and conventional tablets (same daily dosage administered in 2 divided doses 4 hours apart).4

Comparable plasma concentrations achieved following single-dose administration of dexmethylphenidate hydrochloride capsules or single-dose administration of racemic methylphenidate hydrochloride capsules at equimolar doses (twice the total mg amount of dexmethylphenidate hydrochloride).1

Food

Conventional tablets: High-fat meal slows rate of absorption but does not alter peak concentration or extent of absorption compared with administration in fasting state.1

Extended-release capsules: Effects of food on absorption characteristics not studied but thought to be similar to those observed with similar extended-release formulation of racemic methylphenidate.4 Administration of extended-release racemic methylphenidate formulation with high-fat meal results in delayed absorption during first and second absorption phases and lower peak concentration during second absorption phase; extent of absorption not affected.4 Plasma concentration-time profile is similar following administration of extended-release racemic methylphenidate formulation with applesauce compared with administration under fasting conditions.4

Special Populations

Following administration of conventional tablets, AUC is higher in women than in men; pharmacokinetics parameters are similar between boys and girls.1 Following administration of extended-release capsules, peak plasma concentration during first absorption phase is higher in women than in men.4

Following administration of conventional tablets, AUC is lower in children than in adults.1 Pharmacokinetics of extended-release capsules not studied in children; however, following administration of a similar formulation of racemic methylphenidate, between-peak minimum and second peak concentrations were delayed and more variable in children than in adults.4

Distribution

Extent

Not known whether dexmethylphenidate crosses placenta or distributes into milk.1

Elimination

Metabolism

Metabolized principally by de-esterification to form d-ritalinic acid, which has little or no pharmacologic activity.1 4

Elimination Route

Excreted in urine, principally as ritalinic acid.1 4

Half-life

2–3 hours in children or 2–4.5 hours in adults.1 4

Stability

Storage

Oral

Conventional Tablets

25°C (may be exposed to 15–30°C).1 Protect from light and moisture.1

Extended-release Capsules

Tight container at 25°C (may be exposed to 15–30°C).4

Actions

  • Appears to block norepinephrine and dopamine reuptake into the presynaptic neuron and increases their release into the extraneuronal space.1 4 Mechanism of action for treatment of ADHD not determined.1 4

Advice to Patients

  • Provide patient or caregiver with a copy of manufacturer’s patient information (medication guide); discuss and answer questions about its contents as needed.1 4 Instruct patient or caregiver to read and understand contents of medication guide before initiating therapy and each time the prescription is refilled.1 4 6 7

  • Importance of informing clinicians immediately of any adverse cardiovascular (e.g., chest pain, shortness of breath, fainting) or psychiatric effects (e.g., hallucinations, delusional thinking, mania).6 7

  • Importance of taking the drug exactly as prescribed.6 7

  • Importance of not chewing or crushing the beads contained in the capsules and of not storing the sprinkle/food mixture for later use.4 6

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products, as well as any concomitant illnesses/conditions (e.g., glaucoma, cardiac/cardiovascular disease, mental/psychiatric disorder, seizures, suicidal ideation or behaviors, history of substance abuse).1 4 6 7

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 4 6 7

  • Importance of informing patients of other important precautionary information.1 4 6 7 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.1 4

Dexmethylphenidate Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release (containing beads)

5 mg (beads, delayed-release, enteric-coated extended-release 2.5 mg with immediate-release 2.5 mg)

Focalin XR ( C-II)

Novartis

10 mg (beads, delayed-release, enteric-coated extended-release 5 mg with immediate-release 5 mg)

Focalin XR ( C-II)

Novartis

15 mg (beads, delayed-release, enteric-coated extended-release 7.5 mg with immediate-release 7.5 mg)

Focalin XR ( C-II)

Novartis

20 mg (beads, delayed-release, enteric-coated extended-release 10 mg with immediate-release 10 mg)

Focalin XR ( C-II)

Novartis

Tablets

2.5 mg

Focalin ( C-II)

Novartis

5 mg

Focalin ( C-II)

Novartis

10 mg

Focalin ( C-II; dye-free)

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Dexmethylphenidate HCl 10MG Tablets (TEVA PHARMACEUTICALS USA): 30/$43.99 or 90/$119.96

Dexmethylphenidate HCl 2.5MG Tablets (TEVA PHARMACEUTICALS USA): 20/$21.99 or 30/$31.48

Focalin 10MG Tablets (NOVARTIS): 20/$36.97 or 30/$55.46

Focalin 5MG Tablets (NOVARTIS): 20/$28.88 or 30/$43.32

Focalin XR 10MG 24-hr Capsules (NOVARTIS): 20/$121.99 or 30/$181.97

Focalin XR 15MG 24-hr Capsules (NOVARTIS): 20/$121.99 or 30/$182.97

Focalin XR 30MG 24-hr Capsules (NOVARTIS): 20/$126.99 or 30/$187.97

Focalin XR 40MG 24-hr Capsules (NOVARTIS): 30/$199.99 or 90/$575.97

Focalin XR 5MG 24-hr Capsules (NOVARTIS): 20/$116.99 or 30/$173.22

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 2, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Novartis. Focalin (dexmethylphenidate hydrochloride) tablets prescribing information. East Hanover, NJ; 2007 Apr.

2. FDA approval package, Medical review (part 2). Rockville, MD; 2001. From the FDA website.

3. American Academy of Pediatrics Committee on Quality Improvement and Subcommittee on Attention-Deficit/Hyperactivity Disorder. Clinical treatment guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics. 2001; 108:1033-44. [IDIS 470916] [PubMed 11581465]

4. Novartis. Focalin XR (dexmethylphenidate hydrochloride) extended-release capsules prescribing information. East Hanover, NJ; 2007 Apr.

5. American Academy of Child and Adolescent Psychiatry. Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1997; 36(Suppl):85-121S. [PubMed 9000785]

6. Novartis. Focalin XR (dexmethylphenidate hydrochloride) extended-release capsules medication guide. East Hanover, NJ; 2007 Apr.

7. Novartis. Focalin (dexmethylphenidate hydrochloride) tablets medication guide. East Hanover, NJ; 2007 Apr.

8. Food and Drug Administration. FDA Alert: Information for healthcare professionals: Communication about an ongoing safety review of stimulant medications [dexmethylphenidate (marketed as Focalin, Focalin XR), dextroamphetamine (marketed as Dexedrine, Dexedrine Spansules, Dextrostat, and generics), lisdexamfetamine (marketed as Vyvanse), methamphetamine (marketed as Desoxyn), methylphenidate (marketed as Concerta, Daytrana, Metadate CD, Metadate ER, Methylin, Methylin ER, Ritalin, Ritalin-LA, and Ritalin-SR), mixed salts amphetamine (marketed as Adderall and Adderall XR), and pemoline (marketed as Cylert and generics)] used in children with attention-deficit/hyperactivity disorder (ADHD). Rockville, MD; 2009 Jun 23. From the FDA website.

9. Gould MS, Walsh BT, Munfakh JL et al. Sudden death and use of stimulant medications in youths. Am J Psychiatry. 2009; 166:992-1001. [PubMed 19528194]

10. Vitiello B, Towbin K. Stimulant treatment of ADHD and risk of sudden death in children. Am J Psychiatry. 2009; 166:955-7. [PubMed 19528196]

Hide
(web4)