Focalin

Dexmethylphenidate may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• stomach pain
• loss of appetite
• nausea
• vomiting
• heartburn
• weight loss
• dry mouth
• difficulty falling asleep or staying asleep
• dizziness
• drowsiness
• nervousness or jitteriness
• headache

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

• fast, pounding, or irregular heartbeat
• chest pain
• shortness of breath
• excessive tiredness
• slow or difficult speech
• dizziness or faintness
• weakness or numbness of an arm or leg
• changes in vision or blurred vision
• seizures
• believing things that are not true
• feeling unusually suspicious of others
• aggressive behavior
• hallucinations (seeing things or hearing voices that do not exist)
• mood changes
• depression
• motor tics or verbal tics
• swelling of the face, throat, tongue, lips, or eyes
• rash
• hives
• itching
• purple blotches under the skin
• fever
• blistering or peeling skin
• joint pain
• frequent, painful erections
• erection that lasts longer than 4 hours
• numbness, pain, or sensitivity to temperature in the fingers or toes
• skin color change from pale to blue to red in the fingers or toes
• unexplained wounds on the fingers or toes

Dexmethylphenidate may cause sudden death in children and teenagers, especially children and teenagers with heart defects or serious heart problems. This medication also may cause sudden death, heart attack, or stroke in adults, especially adults with heart defects or serious heart problems. Talk to your doctor about the risks of taking this medication.

Dexmethylphenidate may slow children's growth or weight gain. Your child's doctor will watch his or her growth carefully. Talk to your child's doctor if you have concerns about your child's growth or weight gain while he or she is taking this medication. Talk to your child's doctor about the risks of giving dexmethylphenidate to your child.

Dexmethylphenidate may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Yes

Focalin is a prescription medication used to treat attention deficit hyperactivity disorder (ADHD).

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information. 

Focalin is part of the drug class:

• Centrally acting sympathomimetics

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Focalin there are no specific foods that you must exclude from your diet when receiving Focalin.

• Take Focalin exactly as prescribed. Your doctor may adjust the dose until it is right for you.
• Take Focalin tablets twice daily with or without food.
• From time to time, your doctor may stop Focalin treatment for a while to check ADHD symptoms.
• Your doctor may do regular checks of the blood, heart, and blood pressure while taking Focalin. Children should have their height and weight checked often while taking Focalin. Focalin treatment may be stopped if a problem is found during these check-ups.

• Store in a safe place at room temperature, 59 to 86° F (15 to 30° C). 
• Keep and all medicines out of the reach of children.
• Medicines are sometimes prescribed for purposes other than those descibed here. Do not use this medication for a condition for which it was not prescribed. Do not give Focalin to other people, even if they have the same condition. It may harm them and it is against the law.

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.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.1 4

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

• If you have an allergy to dexmethylphenidate, methylphenidate, or any other part of Focalin.
• 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.

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.

Pharmacodynamics

Dexmethylphenidate hydrochloride is a central nervous system stimulant. Focalin, the more pharmacologically active enantiomer of the d- and l-enantiomers, 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.

Effects on QT Interval

The effect of Focalin® XR on the QT interval was evaluated in a double-blind, placebo- and open label active (moxifloxacin)-controlled study following single doses of Focalin XR 40mg in 75 healthy volunteers. ECGs were collected up to 12 hours postdose. Frederica’s method for heart rate correction was employed to derive the corrected QT interval (QTcF). The maximum mean prolongation of QTcF intervals was <5 ms, and the upper limit of the 90% confidence interval was below 10 ms for all time matched comparisons versus placebo. This was below the threshold of clinical concern and there was no evident-exposure response relationship.

Pharmacokinetics

Dexmethylphenidate hydrochloride is readily absorbed following oral administration of Focalin. In patients with ADHD, plasma dexmethylphenidate concentrations increase rapidly, reaching a maximum in the fasted state at about 1 to 1.5 hours postdose. No differences in the pharmacokinetics of Focalin were noted following single and repeated twice daily dosing, thus indicating no significant drug accumulation in children with ADHD.

When given to children as capsules in single doses of 2.5 mg, 5 mg, and 10 mg, Cmax and AUC0-inf of dexmethylphenidate were proportional to dose. In the same study, plasma dexmethylphenidate levels were comparable to those achieved following single dl-threo-methylphenidate HCl doses given as capsules in twice the total mg amount (equimolar with respect to Focalin).

In a single dose study conducted in adults, coadministration of 2 x 10 mg Focalin with a high fat breakfast resulted in a dexmethylphenidate tmax of 2.9 hours postdose as compared to 1.5 hours postdose when given in a fasting state. Cmax and AUC0-inf were comparable in both the fasted and nonfasted states.

Plasma dexmethylphenidate concentrations in children decline exponentially following oral administration of Focalin.

In humans, dexmethylphenidate is metabolized primarily to d-α-phenyl-piperidine acetic acid (also known as d-ritalinic acid) by de-esterification. This metabolite has little or no pharmacological activity. There is little or no in vivo interconversion to the l-threo-enantiomer, based on a finding of minute levels of l-threo-methylphenidate being detectable in a few samples in only 2 of 58 children and adults. After oral dosing of radiolabeled racemic methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was ritalinic acid, accountable for approximately 80% of the dose.

In vitro studies showed that dexmethylphenidate did not inhibit cytochrome P450 isoenzymes.

The mean plasma elimination half-life of dexmethylphenidate is approximately 2.2 hours.

Special Populations

Pharmacokinetic parameters were similar for boys and girls (mean age 10 years).

In a single dose study conducted in adults, the mean dexmethylphenidate AUC0-inf values (adjusted for body weight) following single 2 x 10 mg doses of Focalin were 25%-35% higher in adult female volunteers (n=6) compared to male volunteers (n=9). Both tmax and t1/2 were comparable for males and females.

There is insufficient experience with the use of Focalin to detect ethnic variations in pharmacokinetics.

The pharmacokinetics of dexmethylphenidate after Focalin administration have not been studied in children less than 6 years of age. When single doses of Focalin were given to children between the ages of 6 to 12 years and healthy adult volunteers, Cmax of dexmethylphenidate was similar, however, children showed somewhat lower AUCs compared to the adults.

There is no experience with the use of Focalin in patients with renal insufficiency. After oral administration of radiolabeled racemic methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of ritalinic acid. Since very little unchanged drug is excreted in the urine, renal insufficiency is expected to have little effect on the pharmacokinetics of Focalin.

There is no experience with the use of Focalin in patients with hepatic insufficiency (see PRECAUTIONS, Drug Interactions).

Clinical Studies

Focalin was evaluated in 2 double-blind, parallel-group, placebo-controlled trials in untreated or previously treated patients aged 6 to 17 years old with a DSM-IV diagnosis of Attention Deficit Hyperactivity Disorder (ADHD). Both studies included all 3 subtypes of ADHD, i.e., Combined Type, Predominantly Inattentive Type, or Predominantly Hyperactive-Impulsive Type. While both children and adolescents were included, the sample was predominantly children, thus, the findings are most pertinent to this age group. In both studies, the primary comparison of interest was Focalin versus placebo.

Focalin (5, 10, or 20 mg/day total dose), dl-threo-methylphenidate HCl (10, 20, or 40 mg/day total dose), and placebo were compared in a multicenter, 4-week, parallel group study in n=132 patients. Patients took the study medication twice daily, 3.5 to 5.5 hours between doses. Treatment was initiated with the lowest dose, and doses could be doubled at weekly intervals, depending on clinical response and tolerability, up to the maximum dose. The change from baseline to week 4 of the averaged score (an average of 2 ratings during the week) of the teacher’s version of the SNAP-ADHD Rating Scale, a scale for assessing ADHD symptoms, was the primary outcome. Patients treated with Focalin showed a statistically significant improvement in symptom scores from baseline over patients who received placebo.

Figure 1  Mean Change from Baseline in Teacher SNAP-ADHD Scores in a 4-week Double-Blind Placebo-Controlled Study of Focalin*

*Figure 1: Error bars represent the standard error of the mean.

The other study, involving n=75 patients, was a multicenter, placebo-controlled, double-blind, 2-week treatment withdrawal study in children who were responders during a 6-week, open label initial treatment period. Children took study medication twice a day separated by a 3.5 to 5.5 hour interval. The primary outcome was proportion of treatment failures at the end of the 2-week withdrawal phase, where treatment failure was defined as a rating of 6 (much worse) or 7 (very much worse) on the Investigator Clinical Global Impression - Improvement (CGI-I). Patients continued on Focalin showed a statistically significant lower rate of failure over patients who received placebo.

Figure 2  Percent of Treatment Failures Following a 2-week Double-Blind Placebo-Controlled Withdrawal of Focalin

The premarketing development program for Focalin included exposures in a total of 696 participants in clinical trials (684 patients, 12 healthy adult subjects). These participants received Focalin 5, 10, or 20 mg/day. The 684 ADHD patients (ages 6 to 17 years) were evaluated in 2 controlled clinical studies, 2 clinical pharmacology studies, and 2 uncontrolled long-term safety studies. Safety data on all patients are included in the discussion that follows. Adverse reactions were assessed by collecting adverse events, and results of physical examinations, vital sign and body weight measurements, and laboratory analyses.

Adverse events during exposure were primarily obtained 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 tabulations that follow, standard COSTART dictionary 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 Findings in Clinical Trials with Focalin

No Focalin-treated patients discontinued due to adverse events in 2 placebo-controlled trials. Overall, 50 of 684 children treated with Focalin (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).

Table 1 enumerates treatment-emergent adverse events for 2, placebo-controlled, parallel group trials in children with ADHD at Focalin doses of 5, 10, and 20 mg/day. The table includes only those events that occurred in 5% or more of patients treated with Focalin where the incidence in patients treated with Focalin 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 non-drug factors to the adverse event incidence rate in the population studied.

1 Events, regardless of causality, for which the incidence for patients treated with Focalin was at least 5% and twice the incidence among placebo-treated patients. Incidence has been rounded to the nearest whole number.

Adverse Events from 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 Products

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: nausea

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

Nervous System: dizziness, drowsiness, dyskinesia, headache, rare reports of Tourette’s syndrome, serotonin syndrome in combination with serotonergic drugs, 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 severe hepatic injury

Psychiatric: transient depressed mood, aggressive behavior, libido changes

Skin/subcutaneous: scalp hair loss

Urogenital System: 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.

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 above may also occur.

Controlled Substance Class

Focalin, like other methylphenidate products, is classified as a Schedule II controlled substance by Federal regulation.

Abuse, Dependence, and Tolerance

See WARNINGS for boxed warning containing drug abuse and dependence information.

Focalin®

(dexmethylphenidate hydrochloride tablets) CII

Read the Medication Guide that comes with Focalin® 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.

What Is Focalin?

Focalin is a central nervous system stimulant prescription medicine. It is used for the treatment of attention deficit and hyperactivity disorder (ADHD). Focalin may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.

Focalin should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.

Who should not take Focalin?

Focalin should not be taken if you or your child:

• are very anxious, tense, or agitated
  
• have an eye problem called glaucoma
  
• have tics or Tourette’s syndrome, or a family history of Tourette’s syndrome. Tics are hard to control repeated movements or sounds.
  
• are taking or have taken within the past 14 days an anti-depression medicine called a monoamine oxidase inhibitor or MAOI.
  
• are allergic to anything in Focalin. See the end of this Medication Guide for a complete list of ingredients.

Focalin should not be used in children less than 6 years old because it has not been studied in this age group.

Focalin may not be right for you or your child. Before starting Focalin tell your or your child’s doctor about all health conditions (or a family history of) including:

• heart problems, heart defects, high blood pressure
  
• mental problems including psychosis, mania, bipolar illness, or depression
  
• tics or Tourette’s syndrome
  
• seizures or have had an abnormal brain wave test (EEG)
• circulation problems in fingers or toes

Tell your doctor if you or your child is pregnant, planning to become pregnant, or breastfeeding.

Can Focalin be taken with other medicines?

Tell your doctor about all of the medicines that you or your child takes including prescription and nonprescription medicines, vitamins, and herbal supplements. Focalin 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.

Your doctor will decide whether Focalin can be taken with other medicines.

Especially tell your doctor if you or your child takes:

• anti-depression medicines including MAOIs
  
• seizure medicines
  
• blood thinner medicines
  
• blood pressure medicines
  
• cold or allergy medicines that contain decongestants

Know the medicines that you or your child takes. Keep a list of your medicines with you to show your doctor and pharmacist.

Do not start any new medicine while taking Focalin without talking to your doctor first.

How should Focalin be taken?

• Take Focalin exactly as prescribed. Your doctor may adjust the dose until it is right for you or your child.
  
• Take Focalin twice a day, at least 4 hours apart.
  
• Focalin can be taken with or without food.
  
• From time to time, your doctor may stop Focalin treatment for a while to check ADHD symptoms.
  
• Your doctor may do regular checks of the blood, heart, and blood pressure while taking Focalin. Children should have their height and weight checked often while taking Focalin. Focalin treatment may be stopped if a problem is found during these check-ups.
  
• If you or your child takes too much Focalin or overdoses, call your doctor or poison control center right away, or get emergency treatment.

What are possible side effects of Focalin?

See “What is the most important information I should know about Focalin?” for information on reported heart and mental problems.

Other serious side effects include:

• serious allergic reactions (symptoms can be difficulty breathing, swelling of the face, neck and throat, rashes and hives, fever)
  
• slowing of growth (height and weight) in children
  
• seizures, mainly in patients with a history of seizures
  
• eyesight changes or blurred vision
  
• painful and prolonged erections (priapism) have occurred with methylphenidate. If you or your child develop priapism, seek medical help right away. Because of the potential for lasting damage, priapism should be evaluated by a doctor immediately.

Common side effects include:

• stomach ache       • decreased appetite
  
• nausea             • fever

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 list of possible side effects. Ask your doctor or pharmacist for more information.

How should I store Focalin?

• Store Focalin in a safe place at room temperature, 59°F to 86°F (15°C to 30°C).
  
• Keep Focalin and all medicines out of the reach of children.

General information about Focalin

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Focalin for a condition for which it was not prescribed. Do not give Focalin 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. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Focalin that was written for healthcare professionals. For more information about Focalin call 1-888-669-6682.

What are the ingredients in Focalin?

Active Ingredient: dexmethylphenidate hydrochloride

Inactive Ingredients: pregelatinized starch, lactose monohydrate, sodium starch glycolate, microcrystalline cellulose, magnesium stearate, and FD&C Blue No.1 #5516 aluminum lake (2.5 mg tablets), D&C Yellow Lake #10 (5 mg tablets); the 10 mg tablet contains no dye.

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

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:

Novartis Pharmaceuticals Corporation

East Hanover, NJ 07936

By:

Mikart, Inc.
Atlanta, GA 30318

© Novartis

T2013-120
December 2013

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Dexmethylphenidate may be habit-forming. Never share Focalin 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. Selling or giving away this medicine is against the law.

You may take Focalin with or without food. Take the regular tablet twice daily, at least 4 hours apart. Take the extended-release Focalin XR capsule once daily in the morning.

Do not crush, chew, break, or open an extended-release capsule. Swallow the capsule whole.

To make swallowing easier, you may open the Focalin XR capsule and sprinkle the medicine into a spoonful of applesauce. Swallow right away without chewing. Do not save the mixture for later use.

While using Focalin, your doctor will need to check your progress at regular visits. Your heart rate, blood pressure, height and weight may also need to be checked often.

Store at room temperature away from moisture, heat, and light.

Keep track of your medicine. Dexmethylphenidate is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.