DEXMETHYLPHENIDATE Drug Interactions: What You Need to Know

INTERACTIONS Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed ( 7.1 ).

Halogenated

Anesthetics: Avoid use of dexmethylphenidate hydrochloride tablets on the day of surgery if halogenated anesthetics will be used ( 7.1 ).

7.1 Clinically Important Drug Interactions With Dexmethylphenidate Hydrochloride Tablets Table 2 presents clinically important drug interactions with dexmethylphenidate hydrochloride tablets.

Table

2: Clinically Important Drug Interactions With Dexmethylphenidate Hydrochloride Tablets Monoamine Oxidase Inhibitors (MAOIs)

Clinical Impact

Concomitant use of MAOIs and CNS stimulants, including dexmethylphenidate hydrochloride tablets, 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 tablets 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 tablets may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions ( 5.3 )].

Intervention

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 tablets may increase the risk of sudden blood pressure and heart rate increase during surgery.

Intervention

Monitor blood pressure and avoid use of dexmethylphenidate hydrochloride tablets in patients being treated with anesthetics on the day of surgery. Examples halothane, isoflurane, enflurane, desflurane, sevoflurane Risperidone Clinical Impact Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS)

Intervention

Monitor for signs of EPS

Agitation, marked anxiety, and tension ( 4.1 ) Known hypersensitivity to methylphenidate or product components ( 4.2 ) Glaucoma ( 4.3 ) History of motor tics or a family history or diagnosis of Tourette’s syndrome ( 4.4 ) During, or within a minimum of 14 days following discontinuation of treatment with a monoamine oxidase inhibitor (MAOI) ( 4.5 )

4.1 Agitation Dexmethylphenidate hydrochloride extended-release is contraindicated in patients with marked anxiety, tension, and agitation, since the drug may aggravate these symptoms.

4.2 Hypersensitivity to Methylphenidate Dexmethylphenidate hydrochloride extended-release is contraindicated in patients known to be hypersensitive to methylphenidate, or other components of the product. Hypersensitivity reactions, including angioedema and anaphylactic reactions, have been observed in patients treated with methylphenidate <span class="opacity-50 text-xs">[see Adverse Reactions (6.5 , 6.6 )]</span>.

4.3 Glaucoma Dexmethylphenidate hydrochloride extended-release is contraindicated in patients with glaucoma.

4.4 Tics Dexmethylphenidate hydrochloride extended-release is contraindicated in patients with motor tics or with a family history or diagnosis of Tourette’s syndrome <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>.

4.5 Monoamine Oxidase Inhibitors Dexmethylphenidate hydrochloride extended-release is contraindicated during treatment with monoamine oxidase inhibitors, and also within a minimum of 14 days following discontinuation of treatment with a monoamine oxidase inhibitor (hypertensive crises may result).

AND PRECAUTIONS Serious Cardiovascular Events: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Stimulant products generally should not be used in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious heart problems. ( 5.1 )

Increased Blood

Pressure and Heart Rate: have been reported. Monitor patients for changes in blood pressure and heart rate. Caution should be exercised in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate. ( 5.2 )

Assess Cardiovascular

Status: Prior to stimulant treatment, assess for cardiac disease with history and exam and, if suggested by findings, conduct further cardiac evaluation. Patients with emerging symptoms suggestive of cardiac disease should undergo a prompt cardiac evaluation. ( 5.3 )

Psychotic

Symptoms: may be exacerbated in patients with psychotic disorders. ( 5.4 )

Bipolar

Disorder: Use with particular care in ADHD patients with comorbid Bipolar Disorder. Before initiating stimulant therapy, obtain a detailed psychiatric history for patients with comorbid depressive symptoms, in order to determine risk for Bipolar Disorder. ( 5.5 ) Emergence of New Psychotic or Manic Symptoms: Treatment-emergent psychotic or manic symptoms without a prior history can be caused by stimulants at usual doses. Discontinuation of stimulant therapy may be indicated. ( 5.6 ) Aggression: Monitor for appearance of or worsening of aggressive behavior or hostility. ( 5.7 ) Long-Term Suppression of Growth: Monitor height and weight in pediatric patients at appropriate intervals. Patients who are not growing or gaining weight as expected may need to have their treatment interrupted. ( 5.8 ) Seizures: The threshold for seizures may be lowered. In the presence of seizure, discontinue treatment. ( 5.9 ) 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. ( 5.10 )

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. ( 5.11 )

Visual

Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment. ( 5.12 )

Hematologic

Monitoring: Periodic monitoring of CBC with differential is advised during prolonged therapy. ( 5.14 )

5.1 Sudden Death and Preexisting Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

Adults

Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.

5.2 Hypertension and Other Cardiovascular Conditions Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmHg) and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with preexisting hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.

5.3 Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). 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.

5.4 Preexisting Psychosis Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder.

5.5 Bipolar Illness Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

5.6 Emergence of New Psychotic or Manic Symptoms Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3,482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.

5.7 Aggression Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the post marketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility.

5.8 Long-Term Suppression of Growth Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or nonmedication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and nonmedication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (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. In the 7-week, double-blind, placebo-controlled study of dexmethylphenidate hydrochloride extended-release, the mean weight gain was greater for patients receiving placebo (+0.4 kg) than for patients receiving dexmethylphenidate hydrochloride extended-release (-0.5 kg). Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

5.9 Seizures There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

5.10 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.

5.11 Peripheral Vasculopathy, Including Raynaud’s Phenomenon Stimulants, including dexmethylphenidate hydrochloride extended-release, 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.

5.12 Visual Disturbance Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

5.13 Use in Children Under Six Years of Age Dexmethylphenidate hydrochloride extended-release should not be used in children under 6 years of age, since safety and efficacy in this age group have not been established.

5.14 Hematologic Monitoring Periodic CBC, differential, and platelet counts are advised during prolonged therapy.