Focalin XR

Dosage Forms And Strengths

5 mg extended-release capsules
10 mg extended-release capsules
15 mg extended-release capsules
20 mg extended-release capsules
25 mg extended-release capsules
30 mg extended-release capsules
35 mg extended-release capsules
40 mg extended-release capsules

Storage And Handling

5 mg Extended-Release Capsules (NDC 0078-0430-05) light-blue, (imprinted NVR D5) supplied in bottles of 100

10 mg Extended-Release Capsules (NDC 0078-0431-05) light caramel (imprinted NVR D10) supplied in bottles of 100

15 mg Extended-Release Capsules (NDC 0078-0493-05) green (imprinted NVR D15) supplied in bottles of 100

20 mg Extended-Release Capsules (NDC 0078-0432-05) white (imprinted NVR D20) supplied in bottles of 100

25 mg Extended-Release Capsules (NDC 0078-0608-05) light-blue and white (imprinted NVR D25) supplied in bottles of 100

30 mg Extended-Release Capsules (NDC 0078-0433-05) light caramel and white (imprinted NVR D30) supplied in bottles of 100

35 mg Extended-Release Capsules (NDC 0078-0609-05) light-blue and light caramel (imprinted NVR D35) supplied in bottles of 100

40 mg Extended-Release Capsules (NDC 0078-0434-05) green and white (imprinted NVR D40) supplied in bottles of 100

Store FOCALIN XR at 25°C (77°F), excursions permitted 15°–30°C (59°–86°F). [See USP Controlled Room Temperature.]

Dispense in tight container (USP).

Manufactured for Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936, By Recro Gainesville LLC Gainesville, GA 30504. Revised: June 2015

Take Focalin XR exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. Your doctor will determine the best dose for you.

Capsules:

• For patients new to methylphenidate: Begin treatment with Focalin XR (dexmethylphenidate) at 5 mg/day for children and 10 mg/day for adults, increasing the dose weekly in 5 mg increments for children and in 10 mg increments for adults. Doses above 30 mg/day in children and 40 mg/day in adults have not been studied. 
• For patients already using methylphenidate: Start Focalin XR (dexmethylphenidate) therapy with half (1/2) the current total daily dose of methylphenidate.
• Patients already using Focalin XR  immediate-release tablets: Switch to the same daily dose of Focalin XR extended-release capsules.

Do not use dexmethylphenidate if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

You should not take this medication if you are allergic to dexmethylphenidate or methylphenidate (Ritalin, Concerta), or if you have:

• glaucoma;
• motor tics (twitches);
• a personal or family history of Tourette's syndrome; or
• if you have significant tension, agitation, or anxiety.

Some stimulants have caused sudden death in children and adolescents with serious heart problems or congenital heart defects. Before taking dexmethylphenidate, tell your doctor if you have any type of heart problems.

To make sure you can safely take dexmethylphenidate, tell your doctor if you have any of these other conditions:

• severe depression or a history of mental illness;
• a history of drug or alcohol addiction;
• seizures or epilepsy;
• high blood pressure;
• heart disease, heart rhythm problems, or congestive heart failure; or
• if you have recently had a heart attack.

FDA pregnancy category C. It is not known whether dexmethylphenidate will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether dexmethylphenidate passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Long-term use of dexmethylphenidate can slow a child's growth. Tell your doctor if the child using this medication is not growing or gaining weight properly.

Do not give this medicine to a child younger than 6 years old without medical advice.

Dexmethylphenidate may be habit forming and should be used only by the person for whom it was prescribed. Never share dexmethylphenidate with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

Focalin XR was administered to 46 children and 7 adolescents with ADHD for up to 7 weeks and 206 adults with ADHD in clinical studies. During the clinical studies, 101 adult patients were treated for at least 6 months.

Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and listings that follow, MedDRA terminology has been used to classify reported adverse events. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Adverse Events Associated With Discontinuation Of Treatment In Acute Clinical Studies With Focalin XR-Children

Overall, 50 of 684 children treated with Focalin immediate-release formulation (7.3%) experienced an adverse event 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). None of the 53 Focalin XR-treated pediatric patients discontinued treatment due to adverse events in the 7-week, placebo-controlled study.

Adverse Events Occurring At An Incidence Of 5% Or More Among Focalin XR-Treated Patients-Children

Table 1 enumerates treatment-emergent adverse events for the placebo-controlled, parallel-group study in children and adolescents with ADHD at flexible Focalin XR doses of 5-30 mg/day. The table includes only those events that occurred in 5% or more of patients treated with Focalin XR and for which the incidence in patients treated with Focalin XR was at least twice the incidence in placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse event incidence rate in the population studied.

Table 1: Treatment-Emergent Adverse Events1 Occurring During Double-Blind Treatment-Pediatric Patients

Table 2 below enumerates the incidence of dose-related adverse events that occurred during a fixed-dose, double-blind, placebo-controlled trial of Focalin XR up to 30mg/day versus placebo in children and adolescents with ADHD.

Table 2: Dose-related Adverse Events from a Fixed-dose Study of Double-Blind Treatment in Pediatric Patients by Organ-System and Preferred Term

Adverse Events Associated With Discontinuation Of Treatment In Clinical Studies With Focalin XR-Adults

In the adult placebo-controlled study, 10.7% of the Focalin XR-treated patients and 7.5% of the placebo-treated patients discontinued for adverse events. Among Focalin XR-treated patients, insomnia (1.8%, n=3), feeling jittery (1.8%, n=3), anorexia (1.2%, n=2), and anxiety (1.2%, n=2) were the reasons for discontinuation reported by more than 1 patient.

Adverse Events Occurring At An Incidence Of 5% Or More Among Focalin XR-Treated Patients-Adults

Table 3 enumerates treatment-emergent adverse events for the placebo-controlled, parallel-group study in adults with ADHD at fixed Focalin XR doses of 20, 30, and 40 mg/day. The table includes only those events that occurred in 5% or more of patients in a Focalin XR dose group and for which the incidences in patients treated with Focalin XR appeared to increase with dose. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.

Table 3: Treatment-Emergent Adverse Events1 Occurring During Double-Blind Treatment-Adults

Two other adverse reactions occurring in clinical trials with Focalin XR 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 Focalin XR in the treatment of ADHD.

Table 4: Changes (Mean ± SD) in Vital Signs and Weight by Randomized Dose During Double-Blind Treatment-Adults

Postmarketing Experience

The following additional adverse reactions have been identified during postapproval use of Focalin XR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency:

Musculoskeletal: rhabdomyolysis

Immune System Disorders: hypersensitivity reactions, including angioedema and anaphylaxis

Adverse Events With Other Methylphenidate HCl Dosage Forms

Nervousness and insomnia are the most common adverse reactions reported with other methylphenidate products. In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia may occur more frequently; however, any of the other adverse reactions listed below may also occur.

Other reactions include:

Cardiac: angina, arrhythmia, palpitations, pulse increased or decreased, tachycardia

Gastrointestinal: abdominal pain, nausea

Immune: hypersensitivity reactions including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura

Metabolism/Nutrition: anorexia, weight loss during prolonged therapy

Nervous System: dizziness, drowsiness, dyskinesia, headache, rare reports of Tourette's syndrome, toxic psychosis

Vascular: blood pressure increased or decreased, cerebral arteritis and/or occlusion

Although a definite causal relationship has not been established, the following have been reported in patients taking methylphenidate:

Blood/Lymphatic: leukopenia and/or anemia

Hepatobiliary: abnormal liver function, ranging from transaminase elevation to hepatic coma

Psychiatric: transient depressed mood, aggressive behavior, libido changes

Skin/Subcutaneous: scalp hair loss

Urogenital: priapism

Very rare reports of neuroleptic malignant syndrome (NMS) have been received, and, in most of these, patients were concurrently receiving therapies associated with NMS. In a single report, a 10-year-old boy who had been taking methylphenidate for approximately 18 months experienced an NMS-like event within 45 minutes of ingesting his first dose of venlafaxine. It is uncertain whether this case represented a drug-drug interaction, a response to either drug alone, or some other cause.

Read the entire FDA prescribing information for Focalin XR (Dexmethylphenidate Hydrochloride)

Dexmethylphenidate is used to treat attention deficit hyperactivity disorder (ADHD). It belongs to the group of medicines called central nervous system (CNS) stimulants.

Dexmethylphenidate increases attention and decreases restlessness in patients who are hyperactive, cannot concentrate, or are easily distracted. It is used as part of a total treatment program that also includes social, educational, and psychological therapy.

This medicine is available only with a doctor's prescription. Prescriptions cannot be refilled. A new prescription must be obtained from your doctor each time you need this medicine.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Fast, pounding, or irregular heartbeat

• Blurred vision
• vision changes

• Convulsions
• jerking of the arms and legs
• muscle spasm
• sudden loss of consciousness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• belching
• heartburn
• indigestion
• loss of appetite
• nausea
• stomach discomfort, upset, or pain
• throat pain
• weight loss

• Twitching

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• If you have an allergy to dexmethylphenidate, methylphenidate, or any other part of Focalin XR.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you or a family member have any of these health problems: Blood vessel disease, high blood pressure, heart structure problems or other heart problems, or Tourette's syndrome or tics.
• If you have any of these health problems: Glaucoma; nervous, anxious, or tense state; or overactive thyroid.
• If you have ever had any of these health problems: Drug abuse or stroke.
• If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.
• If you are taking any of these drugs: Linezolid or methylene blue.

This is not a list of all drugs or health problems that interact with Focalin XR.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

     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.

     Hypertension and Other Cardiovascular Conditions

Stimulant medications cause a modest increase in average blood pressure (about 2-4 mmHg) and average heart rate (about 3-6 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.

     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.

     Preexisting Psychosis

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

     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.

     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.

     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.

     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 Focalin XR, the mean weight gain was greater for patients receiving placebo (+0.4 kg) than for patients receiving Focalin XR (-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.

     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.

     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.

     Peripheral Vasculopathy, Including Raynaud’s Phenomenon

Stimulants, including Focalin XR, 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.

     Visual Disturbance

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

     Use in Children Under Six Years of Age

Focalin XR should not be used in children under 6 years of age, since safety and efficacy in this age group have not been established.

     Hematologic Monitoring

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

Applies to dexmethylphenidate: oral capsule extended release, oral tablet

Along with its needed effects, dexmethylphenidate (the active ingredient contained in Focalin XR) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking dexmethylphenidate:

• Fast, pounding, or irregular heartbeat

• Blurred vision
• vision changes

• Convulsions
• jerking of the arms and legs
• muscle spasm
• sudden loss of consciousness

Some side effects of dexmethylphenidate may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• belching
• heartburn
• indigestion
• loss of appetite
• nausea
• stomach discomfort, upset, or pain
• throat pain
• weight loss

• Twitching

Applies to dexmethylphenidate: oral capsule extended release, oral tablet

Cardiovascular

Frequency not reported: Angina, arrhythmia, palpitations, increased or decreased pulse, tachycardia, increased or decreased blood pressure, cerebral arteritis and/or occlusion
Postmarketing reports: Peripheral vasculopathy (including Raynaud's phenomenon)[Ref]

Psychiatric

Very common (10% or more): Psychiatric disorders (up to 46%), insomnia (up to 17%), feeling jittery (up to 12%), anxiety (up to 11%)
Common (1% to 10%): Depression, mood swings, irritability
Frequency not reported: Transient depressed mood, aggressive behavior, libido changes (all reported by patients taking methylphenidate)[Ref]

Nervous system

Very common (10% or more): Nervous system disorders (up to 50%), headache (up to 39%)
Common (1% to 10%): Dizziness
Frequency not reported: Drowsiness, dyskinesia, headache, Tourette's syndrome, toxic psychosis, neuroleptic malignant syndrome (reported by patients taking methylphenidate)[Ref]

Hypersensitivity

Frequency not reported: Hypersensitivity reactions (including angioedema, anaphylaxis, skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura)[Ref]

Musculoskeletal

Postmarketing reports: Rhabdomyolysis

Gastrointestinal

Very common (10% or more): GI disorders (up to 44%), dry mouth (up to 20%), abdominal pain (up to 15%)
Common (1% to 10%): Dyspepsia, nausea, vomiting[Ref]

Metabolic

Very common (10% or more): Metabolism/nutrition disorders (up to 34%), decreased appetite (up to 30%)
Common (1% to 10%): Anorexia
Frequency not reported: Weight loss during prolonged therapy[Ref]

Respiratory

Very common (10% or more): Respiratory/thoracic/mediastinal disorders (up to 16%)
Common (1% to 10%): Nasal congestion, pharyngolaryngeal pain[Ref]

Dermatologic

Common (1% to 10%): Pruritus
Frequency not reported: Scalp hair loss (reported by patients taking methylphenidate)[Ref]

Other

Common (1% to 10%): Fever[Ref]

Genitourinary

Frequency not reported: Priapism (reported by patients taking methylphenidate)

Hematologic

Frequency not reported: Leukopenia and/or anemia (reported by patients taking methylphenidate)[Ref]

Hepatic

Frequency not reported: Abnormal liver function (ranging from transaminase elevation to hepatic coma; reported by patients taking methylphenidate)[Ref]

General

Nervousness and insomnia are the most common adverse reactions reported with other methylphenidate products. In children, the following adverse reactions may occur more frequently: loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia.

Some side effects of Focalin XR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Avoid taking dexmethylphenidate in the evening because it may cause sleep problems (insomnia).

This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.