FOCALIN 20mg. Capsules.

BOXED WARNING

Dexmethylphenidate has a high potential for abuse. Administration of stimulants for a prolonged period of time may lead to physical and psychological drug dependence. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. Caution is advisable in patients with a known history of substance abuse, including alcoholism. Psychotic episodes can occur, especially with parenteral abuse. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion. Symptoms of chronic abuse of dexmethylphenidate may include insomnia, irritability, change in personality, and psychotic symptoms that may be clinically indistinguishable from psychotic disorders, particularly with parenteral or inhalational abuse. Close supervision is required during drug withdrawal from misuse since severe depression may occur. Withdrawal or abrupt discontinuation after chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up. Drug ‘holidays’, the temporary discontinuation of drug during weekends, holidays, summer vacations and etc., is usually not associated with drug withdrawal symptoms, but such holidays are typically reserved for those patients with well-controlled ADHD symptoms. Dexmethylphenidate is not recommended for use in patients with a history of anorexia nervosa or other eating disorders due to its association with reduced appetite and weight loss. Dexmethylphenidate is not FDA-approved for obesity treatment. Misuse of stimulants in any nature may cause sudden death and serious cardiovascular events.

DEA CLASS

Rx, schedule II

DESCRIPTION

CNS stimulant; d-enantiomer of methylphenidate
Used for attention-deficit hyperactivity disorder (ADHD)

COMMON BRAND NAMES

Focalin, Focalin XR

HOW SUPPLIED

Dexmethylphenidate/Dexmethylphenidate Hydrochloride/Focalin Oral Tab: 2.5mg, 5mg, 10mg
Dexmethylphenidate/Dexmethylphenidate Hydrochloride/Focalin XR Oral Cap ER: 5mg, 10mg, 15mg, 20mg, 25mg, 30mg, 35mg, 40mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

20 mg/day PO immediate-release formulation; 40 mg/day PO extended-release formulation.

20 mg/day PO immediate-release formulation; 40 mg/day PO extended-release formulation.

20 mg/day PO immediate-release formulation and 30 mg/day PO extended-release formulation (FDA-approved labeling); however, up to 50 mg/day PO has been used off-label (both formulations).

6 years and older: 20 mg/day PO immediate-release formulation and 30 mg/day PO extended-release formulation (FDA-approved labeling); however, up to 50 mg/day PO has been used off-label (both formulations).
5 years and younger: Safety an efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; use with caution, as dexmethylphenidate is metabolized by the liver.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

ADMINISTRATION

STORAGE

Focalin:
– Protect from light
– Protect from moisture
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
Focalin XR:
– Store at 77 degrees F; excursions permitted to 59-86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

Dexmethylphenidate is contraindicated in patients with known hypersensitivity to dexmethylphenidate, methylphenidate, or any components of these products.

Dexmethylphenidate is contraindicated in patients with marked anxiety, tension, or agitation because the drug can aggravate the symptoms associated with these conditions. Stimulants should be used cautiously in those with bipolar disorder and/or mania due to the potential for manic episodes to occur. An assessment should be performed prior to initiation of therapy to determine the risk for bipolar disorder in patients presenting with symptoms of depression. Due to its toxic effects in overdose, dexmethylphenidate should only be used in those with major depression or suicidal ideation when absolutely necessary. Aggression, hostility, and suicidal ideation or behaviors have been reported in both clinical trials and post-marketing experience with ADHD medications. Although causality has not been established and these behaviors may be inherent to ADHD, close monitoring is recommended. Patients and their caregivers should be advised to promptly report any changes in mood or behavior. If suicide-related events emerge during treatment, consideration should be given to dose reduction or drug discontinuation, especially if symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. In patients with pre-existing psychosis (e.g., schizophrenia), dexmethylphenidate can exacerbate behavioral disturbances and thought disorders. New onset psychotic symptoms may occur in individuals without a prior history of psychosis. If such symptoms occur, discontinuation of treatment should be considered.

Dexmethylphenidate is contraindicated in patients with motor tics, Tourette’s syndrome, or a family history of Tourette’s syndrome because the drug may precipitate motor or phonetic tics.

Dexmethylphenidate is contraindicated in patients with glaucoma, due to the ability of the drug to increase sympathetic stimulation and to raise intraocular pressure. Occasionally, a visual disturbance, such as changes in visual accommodation or blurred vision, has been reported in other individuals without ocular disease.

Dexmethylphenidate has a high potential for abuse. Administration of stimulants for a prolonged period of time may lead to physical and psychological drug dependence. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. Caution is advisable in patients with a known history of substance abuse, including alcoholism. Psychotic episodes can occur, especially with parenteral abuse. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion. Symptoms of chronic abuse of dexmethylphenidate may include insomnia, irritability, change in personality, and psychotic symptoms that may be clinically indistinguishable from psychotic disorders, particularly with parenteral or inhalational abuse. Close supervision is required during drug withdrawal from misuse since severe depression may occur. Withdrawal or abrupt discontinuation after chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up. Drug ‘holidays’, the temporary discontinuation of drug during weekends, holidays, summer vacations and etc., is usually not associated with drug withdrawal symptoms, but such holidays are typically reserved for those patients with well-controlled ADHD symptoms. Dexmethylphenidate is not recommended for use in patients with a history of anorexia nervosa or other eating disorders due to its association with reduced appetite and weight loss. Dexmethylphenidate is not FDA-approved for obesity treatment. Misuse of stimulants in any nature may cause sudden death and serious cardiovascular events.

Use stimulant medications, such as dexmethylphenidate, with caution in patients with pre-existing hypertension, tachycardia, cardiac rhythm disturbances (e.g., ventricular arrhythmias), or other conditions in which a modest increase in blood pressure or heart rate could be detrimental. Stimulant medications cause a modest increase in average blood pressure (approximately 2—4 mmHg) and average heart rate (approximately 3—6 bpm); however, some individuals may have larger increases. Elevated blood pressure may require a dose reduction, discontinuation, and/or initiation of appropriate antihypertensive medication. Periodic blood pressure and heart rate monitoring is recommended in all patients taking dexmethylphenidate.

The FDA recommends that, in general, stimulant medications such as dexmethylphenidate not be used in patients with known serious cardiac structural abnormalities, a history of acute myocardial infarction, aortic stenosis, prosthetic heart valves, valvular heart disease, cardiomyopathy, ventricular dysfunction or heart failure, cardiac arrhythmias, coronary artery disease, advanced arteriosclerosis, or other serious cardiac problems. Stimulant medications may increase blood pressure or heart rate in some individuals; more serious cardiac effects have also been associated with stimulant use. Sudden unexplained death (SUD) and myocardial infarction have occurred in adults receiving stimulants at standard dosages for attention-deficit hyperactivity-disorder (ADHD). Sudden death has also been associated with stimulant medications at usual doses in pediatrics with structural cardiac abnormalities or other serious heart problems. A large retrospective cohort study including over 1.2 million children and young adults 2—24 years of age did not find an increased risk of serious cardiovascular events in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31—1.85). Similar results were seen when current users of ADHD drugs were compared to former users and when current users with severe underlying cardiovascular disease were included in the analysis. The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. The American Heart Association (AHA) states that it is reasonable to consider the use of these medications in pediatric patients with congenital heart disease without current hemodynamic or arrhythmic concerns or congenital heart disease that is considered stable by the patient’s pediatric cardiologist, unless the cardiologist has specific concerns. However, these patients should be closely monitored and treatment discontinuation should be considered if the patient develops any of the following conditions: heart condition associated with sudden cardiac death (SCD), arrhythmia requiring cardiopulmonary resuscitation, direct current cardioversion/defibrillation or overdrive pacing, arrhythmia associated with SCD, any clinically significant arrhythmia that is not treated or controlled, QTc on electrocardiogram (ECG) > 0.46 sec, or heart rate or blood pressure > 2 SD above the mean for age. All patients being considered for treatment with stimulant medications should have a careful history taken, including assessment for a family history of sudden death or ventricular arrhythmias, and a physical exam to assess for the presence of cardiac disease. If cardiac disease is suspected, further cardiac evaluation including an ECG and echocardiogram is warranted. For pediatric patients, the AHA states that it is reasonable to obtain a baseline ECG as a part of the initial evaluation. If a child or adolescent has any significant findings on physical examination, ECG, or family history, consult a pediatric cardiologist before initiating the stimulant medication. Once the medication is started, a repeat ECG may be helpful if the original ECG was obtained before the child was 12 years old, if cardiac symptoms develop, or there is a change in family history.

Stroke has occurred in adults receiving stimulants at usual doses for ADHD ; therefore, patients with cerebrovascular disease should be closely monitored. Stimulant medications may increase blood pressure or heart rate in some individuals.

Children 6 years of age and older have been successfully treated for attention-deficit hyperactivity disorder (ADHD) with dexmethylphenidate; clinical use in infants and children younger than 6 years is not FDA-approved. It should be noted that not all children with ADHD will require medication; non-drug measures are often instituted concurrently with drug therapy. Monitoring of the effectiveness of stimulant therapy by the health care prescriber, parents, and teachers is important; periodic reassessment of the need for medication is recommended. Appropriate stimulant therapy should not suppress normal emotions or intellectual ability; the occurrence of certain side effects may indicate a need for dosage reduction. In psychotic children, dexmethylphenidate may exacerbate behavioral disturbances, psychosis, or thought disorders. New onset psychotic or manic symptoms may develop in children and adolescents receiving therapeutic doses of stimulants. Discontinuation of therapy may be required. Although a direct causal relationship has not been established, aggressive behavior and hostility have been reported during use of some stimulants for ADHD in children. It is recommended to monitor for signs of aggression or worsening of pre-existing aggressive behavior when treatment is initiated. The potential for growth inhibition in pediatric patients should be monitored during stimulant therapy. Monitor height and weight parameters relative to age at treatment initiation and periodically thereafter (at minimum yearly). Patients who are not growing or gaining weight as expected may need to have their treatment interrupted. Data obtained on the effects of stimulants on growth suppression in children 7 to 10 years of age suggested that regularly medicated children (7 days/week) had a temporary average slowing in growth of 2 cm in height and 2.7 kg in weight over 3 years. Data are inadequate to determine whether chronic use of stimulants causes long-term growth inhibition. Although data are limited, available studies do not indicate that stimulant use compromises the attainment of normal adult height and weight in most children. Sudden death has been reported in association with CNS stimulant treatment at usual doses in children with structural cardiac abnormalities or other serious heart problems (e.g., aortic stenosis, cardiomyopathy, congenital heart disease, prosthetic heart valves, valvular heart disease, ventricular dysfunction). Some case reports have involved concomitant medications, such as tricyclic antidepressants. A large retrospective cohort study including over 1.2 million pediatric patients and young adults 2 to 24 years of age did not find an increased risk of serious cardiovascular events, including sudden cardiac death, myocardial infarction, or stroke in current users of drugs for the treatment of ADHD compared to nonusers (adjusted hazard ratio 0.75; 95% CI 0.31 to 1.85). The authors concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. Although some structural cardiac abnormalities alone may carry an increased risk of sudden death, stimulant products generally should not be used in patients with known structural cardiac abnormalities or other serious heart conditions. Exceptions to this warning do exist, but careful screening and monitoring is recommended by the American Heart Association (see separate paragraph detailing cardiac contraindications and precautions).

Caution is advisable during use of dexmethylphenidate in patients with hyperthyroidism or thyrotoxicosis, as sympathomimetic stimulation may induce cardiac arrhythmias or other side effects.

Use dexmethylphenidate with caution in patients with a history of a seizure disorder because the seizure threshold can be reduced, particularly during excess CNS stimulation (i.e., overdosage). The effects of amphetamines on the seizure threshold in normal therapeutic dosages are less clear. Seizure threshold may be reduced in those with EEG abnormalities and rarely in patients without a seizure history or EEG abnormalities. If seizures occur, discontinuation of therapy is recommended.

Dexmethylphenidate is classified as FDA pregnancy risk category C. There are no adequate studies in human pregnancy. It is unclear what effect, if any, the use of stimulants such as dexmethylphenidate would have on the developing fetal central nervous system. Therefore, dexmethylphenidate should be used in pregnancy only when the potential benefit to the mother clearly outweighs the potential risk to the fetus. Teratogenesis has not been observed in animal studies; however, non-teratogenic effects have been noted including delayed skeletal ossification and decreased post-weaning weight gain. At the highest doses tested, plasma levels of dexmethylphenidate in pregnant animals were approximately 1 to 5 times those in adults dosed with 20 mg/day. Teratogenic effects (increased incidence of fetal spina bifida) were observed in rabbits given racemic methylphenidate at a dose 40 times the maximum recommended human dose on a mg/m2 basis. The effects of dexmethylphenidate during labor and delivery are unknown.

According to the manufacturer, it is unknown if dexmethylphenidate is excreted into breast milk, and caution is advisable if the drug is administered to a nursing woman. Dexmethylphenidate has a low molecular weight and should be expected to be excreted in human breast milk by the lactating mother. The effect of stimulant medication exposure via breast milk on the neurological development of the infant has not been well studied. Based on limited information from 4 case reports on the use of racemic methylphenidate during breast-feeding at maternal doses of 35 to 80 mg/day, the calculated infant daily dose for an exclusively breast-fed infant would be about 0.2% to 0.7% of the maternal weight adjusted dose. Although methylphenidate may be considered as an alternative to dexmethylphenidate in breast-feeding women, the medical use of stimulant medications has not been formally evaluated in controlled studies. The AAP has previously considered other stimulants, such as the amphetamines, when used as drugs of abuse, to be contraindicated in breast-feeding due to concerns of irritability and poor sleeping pattern in the infant. If breast-feeding cannot be avoided during the use of stimulant medications, the nursing infant should be monitored for signs of central nervous system hyperactivity, including decreased appetite, insomnia, and irritability. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

The use of dexmethylphenidate may cause dizziness, mask signs of fatigue or the need for rest, or impair the ability of a patient to participate in activities that require mental alertness. Patients should not perform such tasks, including driving or operating machinery, until they are aware of how this medication affects them.

The use of inhalational anesthetics during surgery may sensitize the cardiovascular system to the effects of dexmethylphenidate.

Psychostimulants lower the seizure threshold. Because of a potential increased risk of seizures, psychostimulants should not be used during intrathecal radiographic contrast administration. Dexmethylphenidate therapy should be discontinued 48 hours before and not restarted until at least 24 hours after myelography.

Dexmethylphenidate has not been evaluated in patients with hepatic disease, and caution is recommended.

Debilitated or geriatric patients may be more susceptible to the CNS and sympathomimetic side effects of dexmethylphenidate; use with caution in elderly patients, given the greater incidence of cardiac disease or other conditions in these patients. Extended-release dexmethylphenidate (Focalin XR) has not been systematically studied in the geriatric population. Stimulant medications are used as the treatments of choice in the adult patient over 50 years of age with ADHD when behavioral and lifestyle modifications alone have failed to improve concerns associated with inattention, such as task focus and completion, or organization and time management. Medication should be titrated with low doses initially and with a slow increase. Debilitated or geriatric patients may be more susceptible to the CNS and sympathomimetic side effects of the amphetamines; use with caution in the older adult. Side effects of amphetamines or other stimulants are usually mild but may include mood or behavior changes, tremor, insomnia, increased blood pressure, headache, or gastroesophageal reflux or other GI complaints. Adults should have their blood pressure and heart rate checked at baseline and periodically during treatment. If treatment is considered necessary, periodically re-evaluate the long-term usefulness of the drug for the individual patient. According to the Beers Criteria, methylphenidate and its derivatices are considered potentially inappropriate medications (PIM) for use in geriatric patients with insomnia and should be avoided due to the potential for drug-induced CNS stimulant effects; dexmethylphenidate should be treated with the same caution in patients with insomnia.

Dexmethylphenidate is contraindicated in patients who have received MAOI therapy within the past 14 days because of the possibility of precipitating a hypertensive crisis.

Stimulant medications are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Worsening of peripheral vascular disease is possible. Effects on circulation have been observed with therapeutic doses at different times throughout therapy in all age groups. Signs and symptoms are usually intermittent and mild and generally improve after reduction in dose or discontinuation of drug. However, very rare sequelae include digital skin ulcer and/or soft tissue breakdown. Carefully monitor all patients for digital changes during treatment with stimulant medications, especially those with pre-existing circulation problems. Instruct patients to seek immediate medical attention if any new digital numbness, pain, skin discoloration, or temperature sensitivity occur, or if unexplained wounds appear on their fingers or toes. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.