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Focalin® (dexmethylphenidate hydrochloride) is the d-threo-enantiomer of racemic methylphenidate hydrochloride, which is a 50/50 mixture of the d-threo and l-threo-enantiomers. Focalin is a central nervous system (CNS) stimulant, available in 3 tablet strengths. Each tablet contains dexmethylphenidate hydrochloride 2.5, 5, or 10 mg for oral administration. Dexmethylphenidate hydrochloride is methyl αphenyl-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.
Focalin also contains the following inert 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.
Focalin is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies].
Prior to treating patients with Focalin, assess:
The recommended starting dose of Focalin for pediatric patients who are not currently taking racemic methylphenidate, or for patients who are on stimulants other than methylphenidate, is 5 mg daily (2.5 mg twice daily) with or without food.
The recommended starting dose of Focalin for pediatric patients currently using methylphenidate is half (½) the total daily dose of racemic methylphenidate.
The dose may be titrated weekly in increments of 2.5 mg to 5 mg to a maximum of 20 mg daily (10 mg twice daily). The dose should be individualized according to the needs and response of the patient.
Focalin is administered orally twice daily, at least 4 hours apart.
If paradoxical aggravation of symptoms or other adverse reactions occur, reduce the dosage, or if necessary, discontinue Focalin. If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.
Focalin (dexmethylphenidate hydrochloride) tablets are D-shaped, embossed “D” on upper convex face and dosage strength on lower convex face in the following colors:
Focalin (dexmethylphenidate hydrochloride) tablets (D-shaped, embossed “D” on upper convex face and dosage strength on lower convex face) are available as follows:
2.5 mg tablets (NDC 0078-0380-05) blue, supplied in bottles of 100
5 mg tablets (NDC 0078-0381-05) yellow, supplied in bottles of 100
10 mg tablets (NDC 0078-0382-05) white, supplied in bottles of 100
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
Dispense in tight, light-resistant container (USP).
Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936. Revised: Oct 2023
The following are discussed in more detail in other sections of the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety data in this section is based on data related to Focalin exposure during the premarketing development program 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 open-label long-term safety studies.
Most Common Adverse Reactions (incidence of greater than or equal to 5% and at least twice placebo): abdominal pain, fever, anorexia, and nausea
Adverse Reactions Leading to Discontinuation: Overall, 50 of 684 (7.3%) pediatric patients treated with Focalin experienced an adverse reaction 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 adverse reactions for two, placebo-controlled, parallel group studies in pediatric patients with ADHD taking Focalin doses of 5, 10, and 20 mg/day. The table includes only those reactions that occurred in patients treated with Focalin for which the incidence was at least 5% and twice the incidence among placebo-treated patients.
Table 1: Common Adverse Reactions in Pediatric Patients (6 to 17 years of age) With ADHD
| System organ class | Adverse reactions | Focalin (N = 79) |
Placebo (N = 82) |
| Body as a whole | Abdominal pain | 15% | 6% |
| Fever | 5% | 1% | |
| Digestive system | Anorexia | 6% | 1% |
| Nausea | 9% | 1% | |
| Abbreviation: ADHD, attention deficit hyperactivity disorder. | |||
Abbreviation: ADHD, attention deficit hyperactivity disorder.
The following additional adverse reactions have been identified during postapproval use of dexmethylphenidate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Musculoskeletal: rhabdomyolysis
Immune System Disorders: hypersensitivity reactions, such as angioedema, anaphylactic reactions
The following adverse reactions associated with the use of all Ritalin and Focalin formulations were identified in clinical trials, spontaneous reports, and literature. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.
Infections and Infestations: nasopharyngitis
Blood and the Lymphatic System Disorders: leukopenia, thrombocytopenia, anemia
Immune System Disorders: hypersensitivity reactions, including angioedema and anaphylaxis
Metabolism and Nutrition Disorders: decreased appetite, reduced weight gain, and suppression of growth during prolonged use in pediatric patients
Psychiatric Disorders: insomnia, anxiety, restlessness, agitation, psychosis (sometimes with visual and tactile hallucinations), depressed mood, depression
Nervous System Disorders: headache, dizziness, tremor, dyskinesia, including choreoatheetoid movements, drowsiness, convulsions, cerebrovascular disorders (including vasculitis, cerebral hemorrhages, and cerebrovascular accidents), serotonin syndrome in combination with serotonergic drugs
Eye Disorders: blurred vision, difficulties in visual accommodation
Cardiac Disorders: tachycardia, palpitations, increased blood pressure, arrhythmias, angina pectoris
Respiratory, Thoracic, and Mediastinal Disorders: cough
Gastrointestinal Disorders: dry mouth, nausea, vomiting, abdominal pain, dyspepsia
Hepatobiliary Disorders: abnormal liver function, ranging from transaminase elevation to severe hepatic injury
Skin and Subcutaneous Tissue Disorders: hyperhidrosis, pruritus, urticaria, exfoliative dermatitis, scalp hair loss, erythema multiforme rash, thrombocytopenic purpura
Musculoskeletal and Connective Tissue Disorders: arthralgia, muscle cramps, rhabdomyolysis, trismus
Investigations: weight loss (adult ADHD patients)
Vascular Disorders: peripheral coldness, Raynaud's phenomenon
The list below shows adverse reactions not listed with Ritalin and Focalin formulations that have been reported with other methylphenidate products based on clinical trials data and post-marketing spontaneous reports.
Blood and Lymphatic Disorders: pancytopenia
Immune System Disorders: hypersensitivity reactions, such as auricular swelling
Psychiatric Disorders: affect lability, mania, disorientation, libido changes
Nervous System Disorders: migraine, motor and verbal Tics
Eye Disorders: diplopia, increased intraocular pressure, mydriasis
Cardiac Disorders: sudden cardiac death, myocardial infarction, bradycardia, extrasystole, supraventricular tachycardia, ventricular extrasystole
Respiratory, Thoracic, and Mediastinal Disorders: pharyngolaryngeal pain, dyspnea
Gastrointestinal Disorders: diarrhea, constipation
Skin and Subcutaneous Tissue Disorders: angioneurotic edema, erythema, fixed drug eruption
Musculoskeletal, Connective Tissue, and Bone Disorders: myalgia, muscle twitching
Renal and Urinary Disorders: hematuria
Reproductive System and Breast Disorders: gynecomastia
General Disorders: fatigue
Urogenital Disorders: priapism
Table 2 presents clinically important drug interactions with Focalin.
Table 2: Clinically Important Drug Interactions with Focalin
| Monoamine Oxidase Inhibitors (MAOIs) | |
| Clinical impact | Concomitant use of MAOIs and CNS stimulants, including Focalin, can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see CONTRAINDICATIONS]. |
| Intervention | Concomitant use of Focalin with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. |
| Antihypertensive Drugs | |
| Clinical impact | Focalin may decrease the effectiveness of drugs used to treat hypertension [see WARNINGS AND PRECAUTIONS]. |
| Intervention | Adjust the dosage of the antihypertensive drug as needed. |
| Halogenated Anesthetics | |
| Clinical impact | Concomitant use of halogenated anesthetics and Focalin may increase the risk of sudden blood pressure and heart rate increase during surgery. |
| Intervention | Monitor blood pressure and avoid use of Focalin in patients being treated with anesthetics on the day of surgery. |
| Risperidone | |
| Clinical impact | Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS) |
| Intervention | Monitor for signs of EPS |
Focalin contains dexmethylphenidate hydrochloride, a Schedule II controlled substance.
Focalin has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see WARNINGS AND PRECAUTIONS]. Focalin can be diverted for non-medical use into illicit channels or distribution.
Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.
Misuse and abuse of methylphenidate may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including Focalin, can result in overdose and death [see OVERDOSAGE], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Physical Dependence
Focalin may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including Focalin include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
Tolerance
Focalin may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Included as part of the PRECAUTIONS section.
Focalin has a high potential for abuse and misuse. The use of Focalin exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Focalin can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse And Dependence]. Misuse and abuse of CNS stimulants, including Focalin, can result in overdose and death [see OVERDOSAGE], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing Focalin, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug. Advise patients to store Focalin in a safe place, preferably locked, and instruct patients to not give Focalin to anyone else. Throughout Focalin treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage.
Avoid Focalin use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 beats per minute). Some patients may have larger increases.
Monitor all Focalin-treated patients for hypertension and tachycardia.
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder.
CNS stimulants may induce a manic or mixed mood episode in patients. Prior to initiating Focalin treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).
CNS stimulants, at the recommended dosage, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic, or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0% of placebo-treated patients. If such symptoms occur, consider discontinuing Focalin.
Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate use in both adult and pediatric male patients. Although priapism was not reported with methylphenidate initiation, it developed after some time on methylphenidate, often subsequent to an increase in dosage. Priapism also occurred during methylphenidate withdrawal (drug holidays or during discontinuation).
Focalin-treated patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.
CNS stimulants, including Focalin, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports and at the therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant.
Careful observation for digital changes is necessary during Focalin treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for Focalin-treated patients who develop signs or symptoms of peripheral vasculopathy.
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.
Careful follow-up of weight and height in patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated patients over 36 months (to the ages of 10 to 13 years), suggests that pediatric patients who received methylphenidate for 7 days per week throughout the year had 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 development period.
Closely monitor growth (weight and height) in Focalin-treated pediatric patients. Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
There have been reports of angle closure glaucoma associated with methylphenidate treatment.
Although the mechanism is not clear, Focalin-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.
There have been reports of an elevation of intraocular pressure (IOP) associated with methylphenidate treatment [see ADVERSE REACTIONS].
Prescribe Focalin to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor Focalin-treated patients with a history of abnormally increased IOP or open angle glaucoma.
CNS stimulants, including methylphenidate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported [see ADVERSE REACTIONS].
Before initiating Focalin, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor Focalin-treated patients for the emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically appropriate.
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Educate patients and their families about the risks of abuse, misuse, and addiction of Focalin, which can lead to overdose and death, and proper disposal of any unused drug [see WARNINGS AND PRECAUTIONS, Drug Abuse And Dependence, OVERDOSAGE]. Advise patients to store Focalin in a safe place, preferably locked, and instruct patients to not give Focalin to anyone else.
Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with Focalin use. Instruct patients to contact a healthcare provider immediately if they develop symptoms, such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see WARNINGS AND PRECAUTIONS].
Instruct patients that Focalin can cause elevations of their blood pressure and pulse rate [see WARNINGS AND PRECAUTIONS].
Advise patients that Focalin, at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania [see WARNINGS AND PRECAUTIONS].
Advise patients of the possibility of painful or prolonged penile erections (priapism). Instruct them to seek immediate medical attention in the event of priapism [see WARNINGS AND PRECAUTIONS].
Instruct patients beginning treatment with Focalin about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red. Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.
Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking Focalin. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients [see WARNINGS AND PRECAUTIONS].
Advise patients that Focalin may cause slowing of growth and weight loss [see WARNINGS AND PRECAUTIONS].
Advise patients that IOP and glaucoma may occur during treatment with Focalin [see WARNINGS AND PRECAUTIONS].
Advise patients that motor and verbal tics and worsening of Tourette’s Syndrome may occur during treatment with Focalin. Instruct patients to notify their healthcare provider if emergence of new tics or worsening of tics or Tourette’s syndrome occurs [see WARNINGS AND PRECAUTIONS].
Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to ADHD medications, including Focalin, during pregnancy [see Use In Specific Populations].
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 was seen at a daily dose of approximately 60 mg/kg/day. This dose is approximately 2 times the MRHD of 60 mg/day of racemic methylphenidate given to children on a mg/m² basis. 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, which is approximately 4 times the MRHD (children) of 60 mg/day of racemic methylphenidate on a mg/m² basis.
In a 24-week carcinogenicity study with racemic methylphenidate in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female 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, in the in vitro mouse lymphoma cell forward mutation assay, or in the in vivo mouse bone marrow micronucleus test. In an in vitro assay using cultured Chinese Hamster Ovary cells treated with racemic methylphenidate, sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response.
No human data on the effect of methylphenidate on fertility are available.
Fertility studies have not been conducted with dexmethylphenidate. 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, approximately 10 times the MRHD of 60 mg/day of racemic methylphenidate given adolescents on a mg/m² basis.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including Focalin, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhdmedications/.
Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There may be risks to the fetus associated with the use of CNS stimulants during pregnancy (see Clinical Considerations). Embryo-fetal development studies in rats showed delayed fetal skeletal ossification at doses up to 5 times the maximum recommended human dose (MRHD) of 20 mg/day given to adults based on plasma levels. A decrease in pup weight in males was observed in a pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 5 times the MRHD of 20 mg/day given to adults based on plasma levels. Plasma levels in adults were comparatively similar to plasma levels in adolescents (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Fetal/Neonatal Adverse Reactions
CNS stimulants, such as Focalin, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers.
Animal Data
In embryo-fetal development studies conducted in rats and rabbits, dexmethylphenidate was administered orally at doses of up to 20 and 100 mg/kg/day, respectively, during the period of organogenesis. No evidence of malformations was found in either the rat or rabbit study; however, delayed fetal skeletal ossification was observed at the highest dose level in rats. When dexmethylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 20 mg/kg/day, post-weaning body weight gain was decreased in male offspring at the highest dose, but no other effects on postnatal development were observed. At the highest doses tested, plasma levels [area under the curves (AUCs)] of dexmethylphenidate in pregnant rats and rabbits were approximately 5 and 1 times, respectively, those in adults dosed with the MRHD of 20 mg/day.
Racemic methylphenidate has been shown to cause malformations (increased incidence of fetal spina bifida) in rabbits when given in doses of 200 mg/kg/day throughout organogenesis.
Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Limited published literature, based on milk sampling from seven mothers’ reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7. There are no reports of adverse effects on the breastfed infant and no effects on milk production. Long-term neurodevelopmental effects on infants from stimulant exposure are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Focalin and any potential adverse effects on the breastfed infant from Focalin or from the underlying maternal condition.
Monitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain.
The safety and effectiveness of Focalin have been established in pediatric patients aged 6 to 17 years in two adequate and well-controlled clinical trials [see Clinical Studies].
The safety and effectiveness of Focalin in pediatric patients aged less than 6 years have not been established. The long-term efficacy of Focalin in pediatric patients has not been established.
Growth should be monitored during treatment with stimulants, including Focalin. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see WARNINGS AND PRECAUTIONS].
Rats treated with racemic methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. A deficit in acquisition of a specific learning task was observed in females only. The doses at which these findings were observed are at least 6 times the MRHD of 60 mg/day given to children on a mg/m² basis.
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 to 14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 4 times the MRHD of 60 mg of racemic methylphenidate given to children 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 (8 times the MRHD given to children on a mg/m² basis). The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (approximately 0.5 times the MRHD given to children on a mg/m² basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.
Focalin has not been studied in the geriatric population.
Overdose of CNS stimulants is characterized by the following sympathomimetic effects:
Consider the possibility of multiple drug ingestion. Because methylphenidate has a large volume of distribution and is rapidly metabolized, dialysis is not useful. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
Dexmethylphenidate hydrochloride is a CNS stimulant. The mode of therapeutic action in ADHD is not known.
Dexmethylphenidate is the more pharmacologically active d-enantiomer of racemic methylphenidate. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.
A formal QT study has not been conducted in patients taking Focalin; however, a large QT effect is not expected. At the recommended maximum total daily dosage of 40 mg, Focalin XR (dexmethylphenidate) extended-release capsule does not prolong the QTc interval to any clinically relevant extent.
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.
After single dose administration of Focalin to pediatric patients, dexmethylphenidate exposure (Cmax and AUC0-inf) showed dose-proportional increase in the range of 2.5 mg to 10 mg. Comparable plasma dexmethylphenidate levels were achieved following single dl-threo-methylphenidate HCl doses given as capsules in twice the total mg amount (equimolar with respect to Focalin).
Approximately 90% of the dose is absorbed after oral administration of radiolabeled racemic methylphenidate. However, due to first pass metabolism the mean absolute bioavailability of dexmethylphenidate when administered in various formulations was 22% to 25%.
Effect Of Food
High fat breakfast did not significantly affect Cmax or AUC0-inf of dexmethylphenidate when two 10 mg Focalin tablets were administered, but delayed Tmax from 1.5 hours post dose to 2.9 hours post dose.
The plasma protein binding of dexmethylphenidate is not known; racemic methylphenidate is bound to plasma proteins by 12% to 15%, independent of concentration. Dexmethylphenidate shows a volume of distribution of 2.65 ± 1.11 L/kg.
Plasma dexmethylphenidate concentrations declined exponentially following oral administration of Focalin. Intravenous dexmethylphenidate was eliminated with a mean clearance of 0.40 ± 0.12 L/hr/kg. The mean terminal elimination half-life of dexmethylphenidate was approximately 2.2 hours.
Metabolism
In humans, dexmethylphenidate is metabolized primarily via de-esterification to d-α-phenyl-piperidine acetic acid (also known as d-ritalinic acid). This metabolite has little or no pharmacological activity. There is little or no in vivo interconversion to the l-threo-enantiomer.
Excretion
After oral dosing of radiolabeled racemic methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite of racemic dl-methylphenidate was dl-ritalinic acid, accountable for approximately 80% of the dose. Urinary excretion of parent compound accounted for 0.5% of an intravenous dose.
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 two 10 mg doses of Focalin were 25% to 35% higher in adult female volunteers (n = 6) compared to male volunteers (n = 9). Both Tmax and t½ 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, pediatric patients showed somewhat lower AUCs compared to the adults.
There is no experience with the use of Focalin in patients with renal impairment. Since renal clearance is not an important route of methylphenidate clearance, renal impairment is expected to have little effect on the pharmacokinetics of Focalin.
There is no experience with the use of Focalin in patients with hepatic impairment.
Methylphenidate is not metabolized by cytochrome P450 (CYP) isoenzymes to a clinically relevant extent. Inducers or inhibitors of CYPs are not expected to have any relevant impact on methylphenidate pharmacokinetics. Conversely, the dand l-enantiomers of methylphenidate did not relevantly inhibit CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A. Clinically, methylphenidate coadministration did not increase plasma concentrations of the CYP2D6 substrate desipramine.
The efficacy of Focalin for the treatment of ADHD was established in two double-blind, parallel-group, placebocontrolled trials in untreated or previously treated patients (ages 6 to 17 years old) who met The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for ADHD inattentive, hyperactive-impulsive, or combined inattentive/hyperactive-impulsive subtypes. The sample was predominantly younger (ages 6 to 12 years); thus, the findings are most pertinent to this age group.
In Study 1, patients were randomized to receive either Focalin (5, 10, or 20 mg/day total dose), racemic methylphenidate HCl (10, 20, or 40 mg/day total dose), or placebo in a multicenter, 4-week, parallel group study in 132 pediatric patients. Patients received study medication twice daily separated by a 3.5 to 5.5 hours interval. 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 primary outcome was change from baseline to week 4 of the average score (an average of 2 ratings during the week) of the teacher’s version of the Swanson, Nolan and Pelham (SNAP)-ADHD Rating Scale. This 18 item scale measures ADHD symptoms of inattention and hyperactivity/impulsivity, rated on a scale of 0 (Not at All) to 3 (Very Much). Patients treated with Focalin showed a statistically significant improvement in symptom scores from baseline over patients who received placebo (Table 3).
Table 3: Summary of Efficacy Results From ADHD Acute-Phase Study in Pediatric Patients (6 – 17 years) (Study 1)
| Study number | Treatment group | Primary efficacy measure: teacher SNAP-ADHD total Scorea | |
| Mean baseline score (SD) | Mean change from baseline Week 4 score (SD) | ||
| Study 1 | Focalin 5 - 20 mg/dayb (n = 44) | 1.4 (0.7) (n = 42) |
- 0.7 (0.7) (n = 42) |
| Placebo (n = 42) | 1.6 (0.7) (n = 41) |
- 0.2 (0.7) (n = 39) |
|
| Abbreviations: ADHD, attention deficit hyperactivity disorder; SD, standard deviation; SNAP; swanson, Nolan and Pelham; n, number of patients available at the assessment time point. aAverage of two ratings. bStatistically significantly different from placebo. |
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Study 2 was a multicenter, placebo-controlled, double-blind, 2-week treatment withdrawal study in 75 children (ages 6 to 12 years) 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 (Table 4).
Table 4: Summary of Efficacy Results From ADHD Randomized Withdrawal Study in Pediatric Patients (6 – 17 years) (Study 2)
| Study number | Treatment group | Primary efficacy measure: proportion of treatment failurea | |
| Number of treatment failures /Number of randomized patients | Percentage | ||
| Study 2 | Focalin 5-20 mg/dayb | 6/35 | 17.1% |
| Placebo | 25/40 | 62.5% | |
| Abbreviation: ADHD, attention deficit hyperactivity disorder. aOne patient did not have the value at Visit 10 and hence not included in this analysis. bStatistically significantly different from placebo. |
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FOCALIN®
(foh-kuh-lin)
(dexmethylphenidate hydrochloride) tablets for oral use
What is the most important information I should know about FOCALIN?
FOCALIN may cause serious side effects, including:
Your healthcare provider should check you or your child carefully for heart problems before starting FOCALIN. Tell your healthcare provider if you or your child have any heart problems, heart disease, or heart defects.
Call your healthcare provider or go to the nearest hospital emergency room 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.
All Patients
Tell your healthcare provider about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression.
Call your healthcare provider right away if you or your child have any new or worsening mental symptoms or problems while taking FOCALIN, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.
What is FOCALIN?
FOCALIN is a federally controlled substance (CII) because it contains dexmethylphenidate that can be a target for people who abuse prescription medicines or street drugs. Keep FOCALIN in a safe place to protect it from theft. Never give your FOCALIN to anyone else because it may cause death or harm them. Selling or giving away FOCALIN may harm others and is against the law.
Who should not take FOCALIN?
FOCALIN should not be taken if you or your child:
FOCALIN may not be right for you or your child. Before starting FOCALIN, tell your or your child’s healthcare provider about all health conditions (or a family history of), including:
Tell your healthcare provider about all of the medicines that you or your child takes, including prescription and over-the- counter 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 healthcare provider will decide whether FOCALIN can be taken with other medicines.
Especially tell your healthcare provider if you or your child takes:
Know the medicines that you or your child takes. Keep a list of your medicines with you to show your healthcare provider and pharmacist.
Do not start any new medicine while taking FOCALIN without talking to your healthcare provider first.
How should FOCALIN be taken?
If you or your child take too much FOCALIN, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.
What are the possible side effects of FOCALIN?
FOCALIN may cause serious side effects, including:
Tell your healthcare provider if you or your child have, numbness, pain, skin color change, or sensitivity to temperature in the fingers or toes.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store FOCALIN?
General information about the safe and effective use of FOCALIN.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your pharmacist or healthcare provider for information about FOCALIN that is written for healthcare professionals. 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 symptoms that you have. It may harm them and it is against the law.
What are the ingredients in FOCALIN?
Active ingredient: dexmethylphenidate hydrochloride
Inactive ingredients: 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, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, and sodium starch glycolate.
This Medication Guide has been approved by the U.S. Food and Drug Administration
