Boxed warningThe FDA label of this medicine carries a boxed warning, the strongest warning the FDA gives. Read it under warnings and precautions.
Indications
Dexmethylphenidate Hydrochloride Extended-release Capsules is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies (14) ] . Dexmethylphenidate Hydrochloride Extended-release Capsules is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients aged 6 years and older
Contraindications
Hypersensitivity to methylphenidate or other components of Dexmethylphenidate Hydrochloride Extended-release Capsules. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate [see Adverse Reactions (6.1) ] . Concomitant treatment with monoamine oxidase inhibitors (MAOIs) or within 14 days following discontinuation of treatment with an MAOI, because of the risk of hypertensive crises [see Drug Interactions (7.1) ] .
Known hypersensitivity to methylphenidate or other components of Dexmethylphenidate Hydrochloride Extended-release Capsules ( 4 ) Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days ( 4 )
Warnings and precautions
Serious Cardiovascular Events: Sudden death has been reported in association with CNS stimulant treatment at usual doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infarction have been reported Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm arrhythmias, or coronary artery disease ( 5.2 ).
Blood Pressure and Heart Rate Increases: Monitor blood pressure and pulse. Consider the benefits and risk in patients for whom an increase in blood pressure or heart rate would be problematic ( 5.3 ). Psychiatric Adverse Reactions: Use of stimulants may cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with preexisting psychiatric illness. Evaluate for existing psychotic or bipolar disorder prior to Dexmethylphenidate Hydrochloride Extended-release Capsules use ( 5.4 ).
Priapism: Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed ( 5.5 ). Peripheral Vasculopathy, Including Raynaud’s Phenomenon: Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants ( 5.6 ).
Long-Term Suppression of Growth: Monitor height and weight at appropriate intervals in pediatric patients ( 5.7 ).
5.1Potential for Abuse and Dependence
CNS stimulants, including Dexmethylphenidate Hydrochloride Extended-release Capsules, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Boxed Warning , Drug Abuse and Dependence ( 9.2 , 9.3 )] .
5.2Serious Cardiovascular Reactions
Sudden death, stroke and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, and other serious heart problems.
Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Dexmethylphenidate Hydrochloride Extended-release Capsules treatment.
5.3Blood Pressure and Heart Rate Increases
CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia.
5.4Psychiatric Adverse Reactions Exacerbation of Preexisting Psychosis
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder CNS stimulants may induce a manic or mixed mood episode in patients. Prior to initiating treatment, screen patients for risk factors for developing manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).
New Psychotic or Manic Symptoms CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing Dexmethylphenidate Hydrochloride Extended-release Capsules. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0 in placebo-treated patients.
5.5Priapism Prolonged
and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.
5.6Peripheral Vasculopathy, Including Raynaud's Phenomenon
CNS stimulants, including Dexmethylphenidate Hydrochloride Extended-release Capsules, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment.
Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
5.7Long-Term Suppression of Growth
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. In a 7-week, double-blind, placebo-controlled study of dexmethylphenidate hydrochloride extended-release capsules, the mean weight gain was greater for pediatric patients (ages 6 to 17 years) receiving placebo (+0.4 kg) than for patients receiving dexmethylphenidate hydrochloride extended-release capsules (-0.5 kg).
Careful follow-up of weight and height in pediatric patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated patients over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated pediatric patients (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development.
Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including Dexmethylphenidate Hydrochloride Extended-release Capsules, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
Interactions
Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed ( 7.1 ). Halogenated Anesthetics: Avoid use of Dexmethylphenidate Hydrochloride Extended-release Capsules on the day of surgery if halogenated anesthetics will be used ( 7.1 ).
7.1Clinically Important Interactions with Dexmethylphenidate Hydrochloride Extended-Release Capsules Table
5 presents clinically important drug interactions with Dexmethylphenidate Hydrochloride Extended-release Capsules. Table 5: Clinically Important Drug Interactions with Dexmethylphenidate Hydrochloride Extended-Release Capsules Monoamine Oxidase Inhibitors (MAOI) Clinical Impact Concomitant use of MAOIs and CNS stimulants, including Dexmethylphenidate Hydrochloride Extended-Release Capsules, can cause hypertensive crisis.
Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see Contraindications (4) ] . Intervention Concomitant use of Dexmethylphenidate Hydrochloride Extended-Release Capsules with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Antihypertensive Drugs Clinical Impact Dexmethylphenidate Hydrochloride Extended-Release Capsules may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions (5.3) ] .
Intervention Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed. Examples Potassium-sparing and thiazide diuretics, calcium channel blockers, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta blockers, centrally acting alpha-2 receptor agonists Halogenated Anesthetics Clinical Impact Concomitant use of halogenated anesthetics and Dexmethylphenidate Hydrochloride Extended-Release Capsules may increase the risk of sudden blood pressure and heart rate increase during surgery.
Intervention Avoid use of Dexmethylphenidate Hydrochloride Extended-Release Capsules in patients being treated with anesthetics on the day of surgery. Examples halothane, isoflurane, enflurane, desflurane, sevoflurane
Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including Dexmethylphenidate Hydrochloride Extended-release Capsules, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy registry for ADHD medications at 1-866-961-2388 or visit https://womensmentalhealth.org/adhdmedications/. Risk Summary Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate.
Published studies and post-marketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There may be risks to the fetus associated with the use of CNS stimulants use during pregnancy ( see Clinical Considerations ). Embryo-fetal development studies in rats showed delayed fetal skeletal ossification at doses up to 5 times the maximum recommended human dose (MRHD) of 20 mg/day given to adults based on plasma levels.
A decrease in pup weight in males was observed in a pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 5 times the MRHD of 20 mg/day given to adults based on plasma levels ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions CNS stimulants such as Dexmethylphenidate Hydrochloride Extended-release Capsules, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers.
Animal Data In embryo-fetal development studies conducted in rats and rabbits, dexmethylphenidate was administered orally at doses of up to 20 and 100 mg/kg/day, respectively, during the period of organogenesis. No evidence of malformations was found in either the rat or rabbit study; however, delayed fetal skeletal ossification was observed at the highest dose level in rats. When dexmethylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 20 mg/kg/day, postweaning body weight gain was decreased in male offspring at the highest dose, but no other effects on postnatal development were observed.
At the highest doses tested, plasma levels [area under the curve (AUCs)] of dexmethylphenidate in pregnant rats and rabbits were approximately 5 and 1 times, respectively, those in adults dosed with 20 mg/day. Plasma levels in adults were comparatively similar to plasma levels in adolescents. Racemic methylphenidate has been shown to cause malformations (increased incidence of fetal spina bifida) in rabbits when given in doses of 200 mg/kg/day throughout organogenesis.
Adverse reactions
The following are discussed in more detail in other sections of the labeling: Abuse and Dependence [see Boxed Warning , Warnings and Precautions (5.1) , Drug Abuse and Dependence ( 9.2 , 9.3 )] Known hypersensitivity to methylphenidate or other ingredients of Dexmethylphenidate Hydrochloride Extended-release Capsules [see Contraindications (4) ] Hypertensive Crisis with Concomitant Use of Monoamine Oxidase Inhibitors [see Contraindications (4) , Drug Interactions (7.1) ] Serious Cardiovascular Reactions [see Warnings and Precautions (5.2) ] Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3) ] Psychiatric Adverse Reactions [see Warnings and Precautions (5.4) ] Priapism [see Warnings and Precautions (5.5) ] Peripheral Vasculopathy, including Raynaud’s Phenomenon [see Warnings and Precautions (5.6) ] Long-Term Suppression of Growth [see Warnings and Precautions (5.7) ] The most common adverse reactions (greater than or equal to 5% and twice the rate of placebo): Pediatric patients 6 to 17 years: dyspepsia, decreased appetite, headache, and anxiety ( 6.1 ).
Adults: dry mouth, dyspepsia, headache, pharyngolaryngeal pain, and anxiety ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Clinical Trials Experience with Dexmethylphenidate Hydrochloride Extended-Release Capsules in Pediatric Patients with ADHD The safety data in this section is based on data from a 7-week controlled clinical study of dexmethylphenidate hydrochloride extended-release capsules in 100 (103 randomized) pediatric patients with ADHD ages 6 to 17 years (ages 6 to 12, n = 86; ages 13 to 17, n = 17).
This study was a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the time of onset, duration of efficacy, tolerability, safety of dexmethylphenidate hydrochloride extended-release capsules 5 mg to 30 mg/day who met DSM-IV criteria for ADHD [ see Clinical Studies (14.1) ] . Most Common Adverse Reactions (incidence of greater than or equal to 5% and at least twice placebo): dyspepsia, decreased appetite, headache and anxiety.
Adverse Reactions Leading to Discontinuation : 50 of 684 (7.3%) pediatric patients treated with dexmethylphenidate immediate-release tablets experienced an adverse reaction that resulted in discontinuation. The most common reasons for discontinuation were twitching (described as motor or vocal tics), anorexia, insomnia, and tachycardia (approximately 1% each). Table 1 enumerates adverse reactions for the placebo-controlled, parallel-group study in children and adolescents with ADHD at flexible dexmethylphenidate hydrochloride extended-release capsules doses of 5–30 mg/day.
The table includes only those events that occurred in 5% or more of patients treated with dexmethylphenidate hydrochloride extended-release capsules and for which the incidence in patients treated with dexmethylphenidate hydrochloride extended-release capsules was at least twice the incidence in placebo-treated patients. Table 1: Common Adverse Reactions in Pediatric Patients (6 to 17 years of age) with ADHD Abbreviation: attention deficit hyperactivity disorder.
System Organ Class Adverse Reaction Dexmethylphenidate HCl ER Capsules N=53 Placebo N=47 Gastrointestinal Disorders 38% 19% Dyspepsia 8% 4% Metabolism and Nutrition Disorders 34% 11% Decreased Appetite 30% 9% Nervous System Disorders 30% 13% Headache 25% 11% Psychiatric Disorders 26% 15% Anxiety 6% 0% Table 2 below enumerates the incidence of dose-related adverse reactions that occurred during a fixed-dose, double-blind, placebo-controlled trial in pediatric patients with ADHD taking dexmethylphenidate hydrochloride extended-release capsules up to 30 mg daily versus placebo.
The table includes only those reactions that occurred in patients treated with dexmethylphenidate hydrochloride extended-release capsules for which the incidence was at least 5% and greater than the incidence among placebo-treated patients. Table 2: Dose-Related Adverse Reactions in Pediatric Patients (6 to 17 years of age) with ADHD Abbreviation: attention deficit hyperactivity disorder. System Organ Class Adverse Reaction Dexmethylphenidate HCl ER Capsules Dexmethylphenidate HCl ER Capsules Dexmethylphenidate HCl ER Capsules Placebo 10 mg/d N=64 20 mg/d N=60 30 mg/d N=58 N=63 Gastrointestinal Disorders 22% 23% 29% 24% Vomiting 2% 8% 9% 0% Metabolism and Nutritional Disorders 16% 17% 22% 5% Anorexia 5% 5% 7% 0% Psychiatric Disorders 19% 20% 38% 8% Insomnia 5% 8% 17% 3% Depression 0% 0% 3% 0% Mood Swings 0% 0% 3% 2% Other Adverse Reactions Irritability 0% 2% 5% 0% Nasal Congestion 0% 0% 5% 0% Pruritus 0% 0% 3% 0% Clinical Trials Experience With Dexmethylphenidate Hydrochloride Extended-Release Capsules in Adult Patients With ADHD The safety data in this section is based on data from a 5-week controlled clinical study of dexmethylphenidate hydrochloride extended-release capsules in 218 adult patients (221 randomized) with ADHD ages 18 to 60 years.
In this study, 101 adult patients were treated for at least 6 months. This study was a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and tolerability of dexmethylphenidate hydrochloride extended-release capsules 20 mg, 30 mg, or 40 mg daily who met DSM-IV criteria for ADHD [ see Clinical Studies (14.2) ] . Most Common Adverse Reactions (incidence of greater than or equal to 5% and at least twice placebo): dry mouth, dyspepsia, headache, anxiety, and pharyngolaryngeal pain.
Adverse Reactions Leading to Discontinuation : During the double-blind phase of the study, 10.7% of the dexmethylphenidate hydrochloride extended-release capsules - treated patients and 7.5% of the placebo-treated patients discontinued due to adverse reactions. Three patients (1.8%) in the dexmethylphenidate hydrochloride extended-release capsules discontinued due to insomnia and jittery, respectively and two patients (1.2%) in the dexmethylphenidate hydrochloride extended-release capsules discontinued due to anorexia and anxiety, respectively.
Table 3 enumerates adverse reactions for the placebo-controlled, parallel-group study in adults with ADHD at fixed dexmethylphenidate hydrochloride extended-release capsules doses of 20, 30, and 40 mg/day. The table includes only those events that occurred in 5% or more of patients in a dexmethylphenidate hydrochloride extended-release capsules dose group and for which the incidences in patients treated with dexmethylphenidate hydrochloride extended-release capsules appeared to increase with dose.
Table 3: Dose-Related Adverse Reactions in Adult Patients (18 to 60 years of age) with ADHD System Organ Class Adverse Reaction Dexmethylphenidate HCl ER Capsules 20 mg N=57 Dexmethylphenidate HCl ER Capsules 30 mg N=54 Dexmethylphenidate HCl ER Capsules 40 mg N=54 Placebo N=53 Gastrointestinal Disorders 28% 32% 44% 19% Dry Mouth 7% 20% 20% 4% Dyspepsia 5% 9% 9% 2% Nervous System Disorders 37% 39% 50% 28% Headache 26% 30% 39% 19% Psychiatric Disorders 40% 43% 46% 30% Anxiety 5% 11% 11% 2% Respiratory, Thoracic and Mediastinal Disorders 16% 9% 15% 8% Pharyngolaryngeal Pain 4% 4% 7% 2% Two other adverse reactions occurring in clinical trials with dexmethylphenidate hydrochloride extended-release capsules at a frequency greater than placebo, but which were not dose related were: feeling jittery (12% and 2%, respectively) and dizziness (6% and 2%, respectively).
Table 4 summarizes changes in vital signs and weight that were recorded in the adult study (N = 218) of dexmethylphenidate hydrochloride extended-release
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
DEXMETHYLPHENIDATE HYDROCHLORIDE 15MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
