Focalin® XR (dexmethylphenidate hydrochloride) extended-release capsules is an extended-release formulation of dexmethylphenidate with a bi-modal release profile. Focalin® XR uses the proprietary SODAS® (Spheroidal Oral Drug Absorption System) technology. Each bead-filled Focalin XR capsule contains half the dose as immediate-release beads and half as enteric-coated, delayed-release beads, thus providing an immediate release of dexmethylphenidate and a second delayed release of dexmethylphenidate. Focalin XR is available as 5, 10, 15, and 20 mg extended-release capsules. Focalin XR 5, 10, 15, and 20 mg extended-release capsules provide in a single dose the same amount of dexmethylphenidate as dosages of 2.5, 5, 7.5 or 10 mg of Focalin® given b.i.d. as tablets.
Dexmethylphenidate hydrochloride, the d-threo enantiomer of racemic methylphenidate hydrochloride, is a central nervous system (CNS) stimulant.
Dexmethylphenidate hydrochloride is methyl α-phenyl-2-piperidineacetate hydrochloride, (R,R’)-(+)-. Its empirical formula is C14H19NO2•HCl. Its molecular weight is 269.77 and its structural formula is
Note: * = asymmetric carbon centers
Dexmethylphenidate hydrochloride is a white to off white powder. Its solutions are acid to litmus. It is freely soluble in water and in methanol, soluble in alcohol, and slightly soluble in chloroform and in acetone.
Inactive ingredients: ammonio methacrylate copolymer, FD&C Blue #2 (5 mg and 15 mg strengths), FDA/E172 yellow iron oxide (10 mg and 15 mg strengths), gelatin, ink Tan SW-8010, methacrylic acid copolymer, polyethylene glycol, sugar spheres, talc, titanium dioxide, and triethyl citrate.
Dexmethylphenidate hydrochloride, the active ingredient in Focalin® XR (dexmethylphenidate hydrochloride) extended-release capsules, is a central nervous system stimulant. Dexmethylphenidate, the more pharmacologically active d-enantiomer of racemic methylphenidate, is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known.
The effectiveness of Focalin® XR (dexmethylphenidate hydrochloride) extended-release capsules in the treatment of ADHD was established in randomized, double-blind, placebo-controlled studies in children and adolescents and in adults who met Diagnostic and Statistical Manual 4th edition (DSM-IV) criteria for ADHD (see INDICATIONS AND USAGE).
The effectiveness of Focalin XR was established in a randomized, double-blind, placebo-controlled, parallel-group study in 103 pediatric patients (ages 6 to 12, n=86; ages 13 to 17, n=17) who met DSM-IV criteria for ADHD. Patients were randomized to receive either a flexible dose of Focalin XR (5 to 30 mg/day) or placebo once daily for 7 weeks. During the first 5 weeks of treatment patients were titrated to their optimal dose and in the last 2 weeks of the study patients remained on their optimal dose without dose changes or interruption.
Signs and symptoms of ADHD were evaluated by comparing the mean change from baseline to endpoint for Focalin XR– and placebo-treated patients using an intent-to-treat analysis of the primary efficacy outcome measure, the DSM-IV total subscale score of the Conners ADHD/DSM-IV Scales for teachers (CADS-T).
There was a statistically significant treatment effect in favor of Focalin XR. There were insufficient adolescents enrolled in this study to assess the efficacy for Focalin XR in the adolescent population. However, pharmacokinetic considerations and evidence of effectiveness of immediate-release Focalin in adolescents support the effectiveness of Focalin XR in this population.
In two additional studies in pediatric patients ages 6-12 who received 20 mg Focalin XR or placebo in a cross-over design, Focalin XR was found to have a statistically significant treatment effect versus placebo on the Swanson, Kotkin, Agler, M-Flynn & Pelham (SKAMP) rating scale combined score at all time points after dosing in each study (1, 2, 4, 6, 8, 9, 10, 11 and 12 hours in one study and 1, 3, 4, 5, 7, 9, 10, 11 and 12 hours in the other study.)
The effectiveness of Focalin XR was established in a randomized, double-blind, placebo-controlled, parallel-group study in 221 adult patients (ages 18 to 60) who met DSM-IV criteria for ADHD. Patients were randomized to receive either a fixed dose of Focalin XR (20, 30, or 40 mg/day) or placebo once daily for 5 weeks. Patients randomized to Focalin XR were initiated on a 10 mg/day starting dose and titrated in increments of 10 mg/week to the randomly assigned fixed dose. Patients were maintained on their fixed dose (20, 30 or 40 mg/day) for a minimum of 2 weeks.
Signs and symptoms of ADHD were evaluated by comparing the mean change from baseline to endpoint for Focalin XR– and placebo-treated patients using an intent-to-treat analysis of the primary efficacy outcome measure, the investigator-administered DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS).
All three Focalin XR doses were statistically significantly superior to placebo. There was no obvious increase in effectiveness with increasing dose.
Focalin® XR (dexmethylphenidate hydrochloride) extended-release capsules is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients aged 6 years and older.
The effectiveness of Focalin XR in the treatment of ADHD in patients aged 6 years and older was established in two placebo-controlled studies in patients meeting DSM-IV criteria for ADHD (see CLINICAL STUDIES).
A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor ulener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; “on the go”; excessive talking; blurting answers; can’t wait turn; intrusive. The Combined Types requires both inattentive and hyperactive-impulsive criteria to be met.
Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the child and not solely on the presence of the required number of DSM-IV characteristics.
Focalin XR is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all children with this syndrome. Stimulants are not intended for use in the child who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician’s assessment of the chronicity and severity of the child’s symptoms.
The effectiveness of Focalin XR for long-term use, i.e., for more than 7 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Focalin XR for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).
Focalin® XR (dexmethylphenidate hydrochloride) extended-release capsules is contraindicated in patients with marked anxiety, tension, and agitation, since the drug may aggravate these symptoms.
Focalin XR is contraindicated in patients known to be hypersensitive to methylphenidate, or other components of the product.
Focalin XR is contraindicated in patients with glaucoma.
Focalin XR is contraindicated in patients with motor tics or with a family history or diagnosis of Tourette’s syndrome. (See ADVERSE REACTIONS.)
Focalin XR 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).
Focalin XR should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during withdrawal from abusive use, since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.
Periodic CBC, differential, and platelet counts are advised during prolonged therapy.
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with dexmethylphenidate and should counsel them in its appropriate use. A patient Medication Guide is available for Focalin XR. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its spans. Patients should be given the opportunity to discuss the spans of the Medication Guide and to obtain answers to any questions they may have. The complete div of the Medication Guide is reprinted at the end of this document.
Focalin XR should not be used in patients being treated (currently or within the preceding two weeks) with MAO Inhibitors (see CONTRAINDICATIONS, Monoamine Oxidase Inhibitors).
Because of possible effects on blood pressure, Focalin XR should be used cautiously with pressor agents.
Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Dexmethylphenidate is metabolized primarily to d-ritalinic acid by de-esterification and not through oxidative pathways.
The effects of gastrointestinal pH alterations on the absorption of dexmethylphenidate from Focalin XR have not been studied. Since the modified release characteristics of Focalin XR are pH dependent, the coadministration of antacids or acid suppressants could alter the release of dexmethylphenidate.
Human pharmacologic studies have shown that racemic methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and tricyclic drugs (e.g., imipramine, clomipramine, desipramine). Downward dose adjustments of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentration (or, in the case of coumarin, coagulation times), when initiating or discontinuing methylphenidate.
Serious adverse events have been reported in concomitant use with clonidine, although no causality for the combination has been established. The safety of using methylphenidate in combination with clonidine or other centrally-acting alpha-2-agonists has not been systematically evaluated.
Lifetime carcinogenicity studies have not been carried out with dexmethylphenidate. In a lifetime carcinogenicity study carried out in B6C3F1 mice, racemic methylphenidate caused an increase in hepatocellular adenomas, and in males only, an increase in hepatoblastomas at a daily dose of approximately 60 mg/kg/day. Hepatoblastoma is a relatively rare rodent malignant tumor type. There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown.
Racemic methylphenidate did not cause any increase in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day.
In a 24-week study of racemic methylphenidate in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Mice were fed diets containing the same concentrations as in the lifetime carcinogenicity study; the high-dose group was exposed to 60-74 mg/kg/day of racemic methylphenidate.
Dexmethylphenidate was not mutagenic in the in vitro Ames reverse mutation assay, the in vitro mouse lymphoma cell forward mutation assay, or the in vivo mouse bone marrow micronucleus test.
Racemic methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or the in vitro mouse lymphoma cell forward mutation assay, and was negative in vivo in the mouse bone marrow micronucleus assay. However, sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay of racemic methylphenidate in cultured Chinese Hamster Ovary (CHO) cells.
Racemic methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week Continuous Breeding study. The study was conducted at doses of up to 160 mg/kg/day.
It is not known whether dexmethylphenidate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if Focalin XR is administered to a nursing woman.
The safety and efficacy of Focalin XR in children under 6 years old have not been established. Long-term effects of Focalin in children have not been well established (see WARNINGS).
In a study conducted in young rats, racemic methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (Postnatal Day 7) and continuing through sexual maturity (Postnatal Week 10). When these animals were tested as adults (Postnatal Weeks 13-14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 6 times the maximum recommended human dose [MRHD] of racemic methylphenidate on a mg/m2 basis) or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose (12 times the racemic MRHD on a mg/m2 basis). The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (half the racemic MRHD on a mg/m2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.
Focalin® XR (dexmethylphenidate hydrochloride) extended-release capsules 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 ulings 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 uled. An event was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.
Focalin® XR (dexmethylphenidate hydrochloride) extended-release capsules, like other methylphenidate products, is classified as a Schedule II controlled substance by Federal regulation.
See WARNINGS for boxed warning containing drug abuse and dependence information.
Signs and symptoms of acute methylphenidate overdosage, resulting principally from overstimulation of the CNS and from excessive sympathomimetic effects, may include the following: vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous membranes.
The physician may wish to consider contacting a poison control center for up-to-date information on the management of overdosage with methylphenidate.
As with the management of all overdosage, the possibility of multiple drug ingestion should be considered.
When treating overdose, practitioners should bear in mind that there is a prolonged release of dexmethylphenidate from Focalin® XR (dexmethylphenidate hydrochloride) extended-release capsules.
Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Gastric spans may be evacuated by gastric lavage as indicated. Before performing gastric lavage, control agitation and seizures if present and protect the airway. Other measures to detoxify the gut include administration of activated charcoal and a cathartic. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for hyperpyrexia.
Efficacy of peritoneal dialysis for Focalin overdosage has not been established.
Focalin® XR (dexmethylphenidate hydrochloride) extended-release capsules is for oral administration once daily in the morning.
Focalin XR may be swallowed as whole capsules or alternatively may be administered by sprinkling the capsule spans on a small amount of applesauce (see specific instructions below). Focalin XR and/or their spans should not be crushed, chewed, or divided.
The capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The mixture of drug and applesauce should be consumed immediately in its entirety. The drug and applesauce mixture should not be stored for future use.
Dosage should be individualized according to the needs and responses of the patients.
The recommended starting dose of Focalin XR for patients who are not currently taking dexmethylphenidate or racemic methylphenidate, or for patients who are on stimulants other than methylphenidate, is 5 mg/day for pediatric patients and 10 mg/day for adult patients.
Dosage may be adjusted in 5 mg increments to a maximum of 20 mg/day for pediatric patients and in 10 mg increments to a maximum of 20 mg/day for adult patients. In general, dosage adjustments may proceed at approximately weekly intervals. The patient should be observed for a sufficient duration at a given dose to ensure that a maximal benefit has been achieved before a dose increase is considered.
For patients currently using methylphenidate, the recommended starting dose of Focalin XR is half the total daily dose of racemic methylphenidate. Patients currently using Focalin (dexmethylphenidate) may be switched to the same daily dose of Focalin XR. The maximum recommended dose is 20 mg/day for pediatric and adult patients.
There is no body of evidence available from controlled trials to indicate how long the patient with ADHD should be treated with Focalin XR. It is generally agreed, however, that pharmacological treatment of ADHD may be needed for extended periods. Nevertheless, the physician who elects to use Focalin XR for extended periods in patients with ADHD should periodically reevaluate the long-term usefulness of the drug for the individual patient with periods off medication to assess the patient’s functioning without pharmacotherapy. Improvement may be sustained when the drug is either temporarily or permanently discontinued.
If paradoxical aggravation of symptoms or other adverse events occur, the dosage should be reduced, or, if necessary, the drug should be discontinued.
If improvement is not observed after appropriate dosage adjustment over a 1-month period, the drug should be discontinued.
Focalin XR capsules 5 mg: light blue (imprinted NVR D5)
Bottles of 100………………………………………………………NDC 0078-0430-05
Focalin XR capsules 10 mg: light caramel (imprinted NVR D10)
Bottles of 100………………………………………………………NDC 0078-0431-05
Focalin XR capsules 15 mg: green (imprinted NVR D15)
Bottles of 100………………………………………………………NDC 0078-0493-05
Focalin XR capsules 20 mg: white (imprinted NVR D20)
Bottles of 100………………………………………………………NDC 0078-0432-05
Store at 25°C (77°F), excursions permitted 15°-30°C (59°-86°F). [See USP Controlled Room Temperature.]
Dispense in tight container (USP).
Focalin® XR is a trademark of Novartis AG
SODAS® is a trademark of Elan Corporation, plc.
This product is covered by US patents including 5,837,284, 5,908,850, 6,228,398, 6,355,656, and 6,635,284.
American Psychiatric Association. Diagnosis and Statistical Manual of Mental Disorders. 4th ed. Washington DC: American Psychiatric Association 1994.
REV: APRIL 2007 T2007-22
(dexmethylphenidate hydrochloride) extended-release capsules CII
Read the Medication Guide that comes with FOCALIN XR® before you or your child starts taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your or your child’s treatment with FOCALIN XR®.
|What is the most important information I should know about FOCALIN XR®?|
The following have been reported with use of dexmethylphenidate hydrochloride and other stimulant medicines.
1. Heart-related problems:
Tell your doctor if you or your child have any heart problems, heart defects, high blood pressure, or a family history of these problems.
Your doctor should check you or your child carefully for heart problems before starting FOCALIN XR®.
Your doctor should check your or your child’s blood pressure and heart rate regularly during treatment with FOCALIN XR®.
Call your doctor right away if you or your child has any signs of heart problems such as chest pain, shortness of breath, or fainting while taking FOCALIN XR®.
2. Mental (Psychiatric) problems:
Children and Teenagers
Tell your doctor about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression.
Call your doctor right away if you or your child have any new or worsening mental symptoms or problems while taking FOCALIN XR®, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.
What Is FOCALIN XR®?
FOCALIN XR® is a central nervous system stimulant prescription medicine. It is used for the treatment of attention deficit and hyperactivity disorder (ADHD). FOCALIN XR® may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.
FOCALIN XR® should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.
|FOCALIN XR® is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep FOCALIN XR® in a safe place to prevent misuse and abuse. Selling or giving away FOCALIN XR® may harm others, and is against the law. |
Tell your doctor if you or your child have (or have a family history of) ever abused or been dependent on alcohol, prescription medicines or street drugs.
Who should not take FOCALIN XR®?
FOCALIN XR® should not be taken if you or your child:
FOCALIN XR® should not be used in children less than 6 years old because it has not been studied in this age group.
FOCALIN XR® may not be right for you or your child. Before starting FOCALIN XR® tell your or your child’s doctor about all health conditions (or a family history of) including:
Tell your doctor if you or your child is pregnant, planning to become pregnant, or breast-feeding.
Can FOCALIN XR® be taken with other medicines?
Tell your doctor about all of the medicines that you or your child take including prescription and nonprescription medicines, vitamins, and herbal supplements. FOCALIN XR® and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking FOCALIN XR®.
Your doctor will decide whether FOCALIN XR® can be taken with other medicines.
Especially tell your doctor if you or your child takes:
Know the medicines that you or your child takes. Keep a ul of your medicines with you to show your doctor and pharmacist.
Do not start any new medicine while taking FOCALIN XR® without talking to your doctor first.
How should FOCALIN XR® be taken?
What are possible side effects of FOCALIN XR®?
See “What is the most important information I should know about FOCALIN XR®?” for information on reported heart and mental problems.
Other serious side effects include:
Common side effects include:
Talk to your doctor if you or your child has side effects that are bothersome or do not go away.
This is not a complete ul of possible side effects. Ask your doctor or pharmacist for more information.
How should I store FOCALIN XR®?
General information about FOCALIN XR®
Medicines are sometimes prescribed for purposes other than those uled in a Medication Guide. Do not use FOCALIN XR® for a condition for which it was not prescribed. Do not give FOCALIN XR® to other people, even if they have the same condition. It may harm them and it is against the law.
This Medication Guide summarizes the most important information about FOCALIN XR®. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about FOCALIN XR® that was written for healthcare professionals. For more information about FOCALIN XR® call 1-888-669-6682.
What are the ingredients in FOCALIN XR®?
Active Ingredient: dexmethylphenidate hydrochloride
Inactive Ingredients: ammonio methacrylate copolymer, FD&C Blue #2 (5 mg and 15mg strengths), FDA/E172 yellow iron oxide (10 mg and 15mg strengths), gelatin, ink Tan SW-8010, methacrylic acid copolymer, polyethylene glycol, sugar spheres, talc, titanium dioxide, and triethyl citrate.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
REV: APRIL 2007 T2007-37
REV: APRIL 2007 Printed in U.S.A. T2007-22/T2007-37
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936
By ELAN HOLDINGS INC.
Gainesville, GA 30504