Dexmethylphenidate Hydrochloride (Page 2 of 8)
5.3 Blood 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 beats per minute). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia.
5.4 Psychiatric 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.
5.5 Priapism
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.
5.6 Peripheral 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 postmarketing 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.
5.7 Long-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.
6 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)]
6.1 Clinical 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 The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (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 hydrochloride 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 to 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.
| System Organ Class Adverse Reaction | Dexmethylphenidate Hydrochloride Extended-Release 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% |
| Abbreviation: ADHD, attention deficit hyperactivity disorder. | ||
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.
| System Organ Class Adverse Reaction | Dexmethylphenidate Hydrochloride Extended-Release Capsules | Dexmethylphenidate Hydrochloride Extended-Release Capsules | Dexmethylphenidate Hydrochloride Extended-Release Capsules | |
| 10 mg/day | 20 mg/day | 30 mg/day | Placebo | |
| N = 64 | N = 60 | 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% |
| Abbreviation: ADHD, attention deficit hyperactivity disorder. | ||||
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 capsule-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.
| System Organ Class Adverse Reaction | Dexmethylphenidate Hydrochloride Extended-Release Capsules, 20 mg | Dexmethylphenidate Hydrochloride Extended-Release Capsules, 30 mg | Dexmethylphenidate Hydrochloride Extended-Release Capsules, 40 mg | Placebo |
| N = 57 | N = 54 | N = 54 | 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 capsules in the treatment of ADHD.
| Dexmethylphenidate Hydrochloride Extended-Release Capsules, 20 mg (N = 57) | Dexmethylphenidate Hydrochloride Extended-Release Capsules, 30 mg (N = 54) | Dexmethylphenidate Hydrochloride Extended-Release Capsules, 40 mg (N = 54) | Placebo (N = 53) | |
| Pulse (bpm) | 3.1 ± 11.1 | 4.3 ± 11.7 | 6.0 ± 10.1 | -1.4 ± 9.3 |
| Diastolic BP (mmHg) | -0.2 ± 8.2 | 1.2 ± 8.9 | 2.1 ± 8.0 | 0.3 ± 7.8 |
| Weight (kg) | -1.4 ± 2.0 | -1.2 ± 1.9 | -1.7 ± 2.3 | -0.1 ± 3.9 |
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