DailyMed Label: methylphenidate hydrochloride CD

DailyMed Label: methylphenidate hydrochloride CD

2021

DailyMed Prescription

methylphenidate hydrochloride CD

methylphenidate hydrochloride

Lannett Company, Inc.

NDC: 0527-4579

NDC: 0527-4579

NDC: 0527-4580

NDC: 0527-4580

NDC: 0527-4581

NDC: 0527-4581

NDC: 0527-4582

NDC: 0527-4582

NDC: 0527-4583

NDC: 0527-4583

NDC: 0527-4584

NDC: 0527-4584

Methylphenidate HCl Extended-Release Capsules CD is a central nervous system (CNS) stimulant. The extended-release capsules comprise both immediate-release (IR) and extended-release (ER) beads such that 30% of the dose is provided by the IR component and 70% of the dose is provided by the ER component. Methylphenidate HCl Extended-Release Capsules CD is available in six capsule strengths containing 10 mg (3 mg IR; 7 mg ER), 20 mg (6 mg IR; 14 mg ER), 30 mg (9 mg IR; 21 mg ER), 40 mg (12 mg IR; 28 mg ER), 50 mg (15 mg IR; 35 mg ER), or 60 mg (18 mg IR; 42 mg ER) of methylphenidate hydrochloride for oral administration. Chemically, methylphenidate HCl is d,l (racemic)- threo -methyl α-phenyl-2-piperidineacetate hydrochloride. Its empirical formula is C 14 H 19 NO 2 •HCl. Its structural formula is: Methylphenidate HCl USP is a white, odorless, crystalline 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. Its molecular weight is 269.77. Methylphenidate HCl Extended-Release Capsules CD also contains the following inert ingredients: Sugar spheres, povidone, hydroxypropylmethylcellulose and polyethylene glycol, ethylcellulose aqueous dispersion, dibutyl sebacate, gelatin, and titanium dioxide. The individual capsules contain the following color agents: 10 mg capsules: FD&C Blue No. 2, FDA/E172 Yellow Iron Oxide 20 mg capsules: FD&C Blue No. 2 30 mg capsules: FD&C Blue No. 2, FDA/E172 Red Iron Oxide 40 mg capsules: FDA/E172 Yellow Iron Oxide 50 mg capsules: FD&C Blue No. 2, FDA/E172 Red Iron Oxide Chemical Structure

Methylphenidate HCl Extended-Release Capsules CD are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). The efficacy of Methylphenidate HCl Extended-Release Capsules CD in the treatment of ADHD was established in one controlled trial of children aged 6 to 15 who met DSM-IV criteria for ADHD (see CLINICAL PHARMACOLOGY ). 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 listener; 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. Methylphenidate HCl Extended-Release Capsules CD 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 Methylphenidate HCl Extended-Release Capsules CD for long-term use, i.e., for more than 3 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Methylphenidate HCl Extended-Release Capsules CD for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION ).

Methylphenidate HCl Extended-Release Capsules CD is administered once daily in the morning, before breakfast. Methylphenidate HCl Extended-Release Capsules CD may be swallowed whole with the aid of liquids, or alternatively, the capsule may be opened and the capsule contents sprinkled onto a small amount (tablespoon) of applesauce and given immediately, and not stored for future use. Drinking some fluids, e.g. water, should follow the intake of the sprinkles with applesauce. The capsules and the capsule contents must not be crushed or chewed (see PRECAUTIONS: Information For Patients ). Patients should be advised to avoid alcohol while taking Methylphenidate HCl Extended-Release Capsules CD. Dosage should be individualized according to the needs and responses of the patient. The recommended starting dose of Methylphenidate HCl Extended-Release Capsules CD is 20 mg once daily. Dosage may be adjusted in weekly 10-20 mg increments to a maximum of 60 mg/day taken once daily in the morning, depending upon tolerability and degree of efficacy observed. Daily dosage above 60 mg is not recommended. There is no body of evidence available from controlled trials to indicate how long the patient with ADHD should be treated with Methylphenidate HCl Extended-Release Capsules CD. It is generally agreed, however, that pharmacological treatment of ADHD may be needed for extended periods. Nevertheless, the physician who elects to use Methylphenidate HCl Extended-Release Capsules CD for extended periods in patients with ADHD should periodically re-evaluate the long-term usefulness of the drug for the individual patient with trials 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 one-month period, the drug should be discontinued.

Methylphenidate HCl Extended-Release Capsules CD is contraindicated in patients with marked anxiety, tension and agitation, since the drug may aggravate these symptoms. Methylphenidate HCl Extended-Release Capsules CD is contraindicated in patients known to be hypersensitive to methylphenidate or other components of the product. Methylphenidate HCl Extended-Release Capsules CD contains sucrose. Therefore, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicine. Methylphenidate HCl Extended-Release Capsules CD is contraindicated in patients with glaucoma. Methylphenidate HCl Extended-Release Capsules CD is contraindicated in patients with motor tics or with a family history or diagnosis of Tourette's syndrome (see ADVERSE REACTIONS ). Methylphenidate HCl Extended-Release Capsules CD is contraindicated during treatment with monoamine oxidase inhibitors, and also within a minimum of 14 days following discontinuation of a monoamine oxidase inhibitor (hypertensive crises may result). Methylphenidate HCl Extended-Release Capsules CD is contraindicated in patients with severe hypertension, angina pectoris, cardiac arrhythmias, heart failure, recent myocardial infarction, hyperthyroidism or thyrotoxicosis (see WARNINGS ). There is a risk of sudden blood pressure increase during surgery. If surgery is planned, Methylphenidate HCl Extended-Release Capsules CD should not be taken on the day of the surgery.

Periodic CBC, differential, and platelet counts are advised during prolonged therapy. Methylphenidate HCl Extended-Release Capsules CD contains methylphenidate which may result in a positive result during drug testing. Patients should be instructed to take one dose in the morning before breakfast. The patients should be instructed that the capsule may be swallowed whole, or alternatively, the capsule may be opened and the capsule contents sprinkled onto a small amount (tablespoon) of applesauce and given immediately, and not stored for future use. The capsules and the capsule contents must not be crushed or chewed. Patients should be advised to avoid alcohol while taking Methylphenidate HCl Extended-Release Capsules CD. Consumption of alcohol while taking Methylphenidate HCl Extended-Release Capsules CD may result in a more rapid release of the dose of methylphenidate. Advise patients, caregivers, and family members of the possibility of painful or prolonged penile erections (priapism). Instruct the patient to seek immediate medical attention in the event of priapism. Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon] Instruct patients beginning treatment with Methylphenidate HCl Extended-Release Capsules CD 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 Methylphenidate HCl Extended-Release Capsules CD. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with methylphenidate and should counsel them in its appropriate use. A patient Medication Guide is available for Methylphenidate HCl Extended-Release Capsules CD. The prescriber or healthcare professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. The Medication Guide may also be obtained by calling 1-844-834-0530. Monoamine Oxidase Inhibitors (MAOI) Concomitant use of MAOIs and CNS stimulants, including Methylphenidate HCl Extended-Release Capsules CD can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure (see CONTRAINDICATIONS ). Concomitant use of Methylphenidate HCl Extended-Release Capsules CD with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. Antihypertensive Drugs Methylphenidate HCl Extended-Release Capsules CD may decrease the effectiveness of drugs used to treat hypertension. Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed. Because of possible effects on blood pressure, Methylphenidate HCl Extended-Release Capsules CD should be used cautiously with pressor agents. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), phenylbutazone and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). Downward dose adjustment of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentrations (or, in the case of coumarin, coagulation times), when initiating or discontinuing concomitant methylphenidate. In theory, there is a possibility that the clearance of methylphenidate might be affected by urinary pH, either being increased with acidifying agents or decreased with alkalizing agents. This should be considered when methylphenidate is given in combination with agents that alter urinary pH. 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). Monitor for signs of EPS. In a lifetime carcinogenicity study carried out in B6C3F1 mice, 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. This dose is approximately 30 times and 4 times the maximum recommended human dose of Methylphenidate HCl Extended-Release Capsules CD on a mg/kg and mg/m 2 basis, respectively. 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. Methylphenidate did not cause any increases 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 22 times and 5 times the maximum recommended human dose of Methylphenidate HCl Extended-Release Capsules CD on a mg/kg and mg/m 2 basis, respectively. In a 24-week carcinogenicity study 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 concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 to 74 mg/kg/day of methylphenidate. Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or in the in vitro mouse lymphoma cell forward mutation assay. Sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay in cultured Chinese Hamster Ovary cells. Methylphenidate was negative in vivo in males and females in the mouse bone marrow micronucleus assay. 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 up to 160 mg/kg/day, approximately 80-fold and 8-fold the highest recommended human dose of Methylphenidate HCl Extended-Release Capsules CD on a mg/kg and mg/m 2 basis, respectively. Methylphenidate has been shown to have teratogenic effects in rabbits when given in doses of 200 mg/kg/day, which is approximately 100 times and 40 times the maximum recommended human dose on a mg/kg and mg/m 2 basis, respectively. A reproduction study in rats revealed no evidence of teratogenicity at an oral dose of 58 mg/kg/day. However, this dose, which caused some maternal toxicity, resulted in decreased postnatal pup weights and survival when given to the dams from day one of gestation through the lactation period. This dose is approximately 30 fold and 6 fold the maximum recommended human dose of Methylphenidate HCl Extended-Release Capsules CD on a mg/kg and mg/m 2 basis, respectively. There are no adequate and well-controlled studies in pregnant women. Methylphenidate HCl Extended-Release Capsules CD should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether methylphenidate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if Methylphenidate HCl Extended-Release Capsules CD is administered to a nursing woman. The safety and efficacy of Methylphenidate HCl Extended-Release Capsules CD in children under 6 years old have not been established. Long-term effects of methylphenidate in children have not been well established (see WARNINGS ).

The premarketing development program for Methylphenidate HCl Extended-Release Capsules CD included exposures in a total of 228 participants in clinical trials (188 pediatric patients with ADHD, 40 healthy adult subjects). These participants received Methylphenidate HCl Extended-Release Capsules CD 20, 40, and/or 60 mg/day. The 188 patients (ages 6 to 15) were evaluated in one controlled clinical study, one controlled, crossover clinical study, and one uncontrolled clinical study. Safety data on all patients are included in the discussion that follows. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, and ECGs.

Monoamine Oxidase Inhibitors (MAOI) Concomitant use of MAOIs and CNS stimulants, including Methylphenidate HCl Extended-Release Capsules CD can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure (see CONTRAINDICATIONS ). Concomitant use of Methylphenidate HCl Extended-Release Capsules CD with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. Antihypertensive Drugs Methylphenidate HCl Extended-Release Capsules CD may decrease the effectiveness of drugs used to treat hypertension. Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed. Because of possible effects on blood pressure, Methylphenidate HCl Extended-Release Capsules CD should be used cautiously with pressor agents. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), phenylbutazone and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). Downward dose adjustment of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentrations (or, in the case of coumarin, coagulation times), when initiating or discontinuing concomitant methylphenidate. In theory, there is a possibility that the clearance of methylphenidate might be affected by urinary pH, either being increased with acidifying agents or decreased with alkalizing agents. This should be considered when methylphenidate is given in combination with agents that alter urinary pH. 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). Monitor for signs of EPS.

Methylphenidate HCl Extended-Release Capsules CD are available in six strengths: 10 mg, green/white capsules, imprinted with “LANNETT 4579” in white letters on the green cap, and “10 mg” in black letters on the white body of the capsule. NDC 0527-4579-37 Bottle of 100 Capsules 20 mg, blue/white capsules, imprinted with “LANNETT 4580” in white letters on the blue cap, and “20 mg” in black letters on the white body of the capsule. NDC 0527-4580-37 Bottle of 100 Capsules 30 mg, reddish-brown/white capsules, imprinted with “LANNETT 4581” in white letters on the reddish-brown cap, and “30 mg” in black letters on the white body of the capsule. NDC 0527-4581-37 Bottle of 100 Capsules 40 mg, yellow ivory/white capsules, imprinted with “LANNETT 4582” in black letters on the yellow ivory cap, and “40 mg” in black letters on the white body of the capsule. NDC 0527-4582-37 Bottle of 100 Capsules 50 mg, purple/white capsules, imprinted with “LANNETT 4583” in white letters on the purple cap, and “50 mg” in black letters on the white body of the capsule. NDC 0527-4583-37 Bottle of 100 Capsules 60 mg, white/white capsules, imprinted with “LANNETT 4584” in black letters on the white cap, and “60 mg” in black letters on the white body of the capsule. NDC 0527-4584-37 Bottle of 100 Capsules Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature]. Keep out of the reach of children.

Methylphenidate HCl is a central nervous system (CNS) stimulant. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. 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. Methylphenidate is a racemic mixture comprised of the d- and l-threo enantiomers. The d-threo enantiomer is more pharmacologically active than the l-threo enantiomer. The pharmacokinetics of the Methylphenidate HCl Extended-Release Capsules CD methylphenidate hydrochloride formulation have been studied in healthy adult volunteers and in children with Attention Deficit Hyperactivity Disorder (ADHD). Methylphenidate is readily absorbed. Methylphenidate HCl Extended-Release Capsules CD has a plasma/time concentration profile showing two phases of drug release with a sharp, initial slope similar to a methylphenidate immediate-release tablet, and a second rising portion approximately three hours later, followed by a gradual decline. (See Figure 1 below.) Methylphenidate HCl Extended-Release Capsules CD was administered as repeated once-daily doses of 20 mg or 40 mg to children aged 7-12 years with ADHD for one week. After a dose of 20 mg, the mean (±SD) early C max was 8.6 (±2.2) ng/mL, the later C max was 10.9 (±3.9) 1 ng/mL and AUC 0-9h was 63.0 (±16.8) ng∙h/mL. The corresponding values after a 40 mg dose were 16.8 (±5.1) ng/mL, 15.1 (±5.8) 1 ng/mL and 120 (±39.6) ng∙h/mL, respectively. The early peak concentrations (median) were reached about 1.5 hours after dose intake, and the second peak concentrations (median) were reached about 4.5 hours after dose intake. The means for C max and AUC following a dose of 20 mg were slightly lower than those seen with 10 mg of the immediate-release formulation, dosed at 0 and 4 hours. FIGURE 1 Comparison of Immediate Release (IR) and Methylphenidate HCl Extended-Release Capsules CD Formulations After Repeated Doses of Methylphenidate HCl in Children with ADHD Figure 1 Following single oral doses of 10-60 mg methylphenidate free base as a solution given to ten healthy male volunteers, C max and AUC increased proportionally with increasing doses. After the 60 mg dose, t max was reached 1.5 hours post-dose, with a mean C max of 31.8 ng/mL (range 24.7-40.9 ng/mL). Following one week of repeated once-daily doses of 20 mg or 40 mg Methylphenidate HCl Extended-Release Capsules CD to children aged 7-12 years with ADHD, C max and AUC were proportional to the administered dose. In a study in adult volunteers to investigate the effects of a high-fat meal on the bioavailability of a dose of 40 mg, the presence of food delayed the early peak by approximately 1 hour (range -2 to 5 hours delay). The plasma levels rose rapidly following the food-induced delay in absorption. Overall, a high-fat meal increased the C max of Methylphenidate HCl Extended-Release Capsules CD by about 30% and AUC by about 17%, on average (see DOSAGE AND ADMINISTRATION ). After a single dose, the bioavailability (C max and AUC) of methylphenidate in 26 healthy adults was unaffected by sprinkling the capsule contents on applesauce as compared to the intact capsule. This finding demonstrates that a 20 mg Methylphenidate HCl Extended-Release Capsules CD capsule, when opened and sprinkled on one tablespoon of applesauce, is bioequivalent to the intact capsule. In humans, methylphenidate is metabolized primarily via deesterification to alpha-phenyl-piperidine acetic acid (ritalinic acid). The metabolite has little or no pharmacologic activity. In vitro studies showed that methylphenidate was not metabolized by cytochrome P450 isoenzymes, and did not inhibit cytochrome P450 isoenzymes at clinically observed plasma drug concentrations. The mean terminal half-life (t ½ ) of methylphenidate following administration of Methylphenidate HCl Extended-Release Capsules CD (t ½ =6.8h) is longer than the mean terminal (t ½ ) following administration of methylphenidate hydrochloride immediate-release tablets (t ½ =2.9h) and methylphenidate hydrochloride sustained-release tablets (t ½ =3.4h) in healthy adult volunteers. This suggests that the elimination process observed for Methylphenidate HCl Extended-Release Capsules CD is controlled by the release rate of methylphenidate from the extended-release formulation, and that the drug absorption is the rate-limiting process. Alcohol Effect An in vitro study was conducted to explore the effect of alcohol on the release characteristics of methylphenidate from the Methylphenidate HCl Extended-Release Capsules CD 60 mg capsule dosage form. At an alcohol concentration of 40% there was an increase in the release rate of methylphenidate in the first hour, resulting in 84% of the methylphenidate being released. The results with the 60 mg capsule are considered to be representative of the other available capsule strengths. Patients should be advised to avoid alcohol while taking Methylphenidate HCl Extended-Release Capsules CD. The pharmacokinetics of methylphenidate after a single dose of Methylphenidate HCl Extended-Release Capsules CD were similar between adult men and women. The influence of race on the pharmacokinetics of methylphenidate after Methylphenidate HCl Extended-Release Capsules CD administration has not been studied. The pharmacokinetics of methylphenidate after Methylphenidate HCl Extended-Release Capsules CD administration have not been studied in children less than 6 years of age. There is no experience with the use of Methylphenidate HCl Extended-Release Capsules CD in patients with renal insufficiency. After oral administration of radiolabeled 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 renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of Methylphenidate HCl Extended-Release Capsules CD. There is no experience with the use of Methylphenidate HCl Extended-Release Capsules CD in patients with hepatic insufficiency.

Methylphenidate HCl Extended-Release Capsules CD was evaluated in a double-blind, parallel-group, placebo-controlled trial in which 321 untreated or previously treated pediatric patients with a DSM-IV diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), 6 to 15 years of age, received a single morning dose for up to 3 weeks. Patients were required to have the combined or predominantly hyperactive-impulsive subtype of ADHD; patients with the predominantly inattentive subtype were excluded. Patients randomized to the Methylphenidate HCl Extended-Release Capsules CD group received 20 mg daily for the first week. Their dosage could be increased weekly to a maximum of 60 mg by the third week, depending on individual response to treatment. The patient's regular school teacher completed the teachers' version of the Conners' Global Index Scale (TCGIS), a scale for assessing ADHD symptoms, in the morning and again in the afternoon on three alternate days of each treatment week. The change from baseline of the overall average (i.e., an average of morning and afternoon scores over 3 days) of the total TCGIS scores during the last week of treatment was analyzed as the primary efficacy parameter. Patients treated with Methylphenidate HCl Extended-Release Capsules CD showed a statistically significant improvement in symptom scores from baseline over patients who received placebo. (See Figure 2.) Separate analyses of TCGIS scores in the morning and afternoon revealed superiority in improvement with Methylphenidate HCl Extended-Release Capsules CD over placebo during both time periods. (See Figure 3.) This demonstrates that a single morning dose of Methylphenidate HCl Extended-Release Capsules CD exerts a treatment effect in both the morning and the afternoon. FIGURE 2 Least Squares Mean Change from Baseline in TCGIS Scores * FIGURE 3 Least Squares Mean Change from Baseline in TCGIS Scores, Morning/Afternoon Groups * Figure 2 Figure 3

NDC 0527-4579-37 Once Daily CII Methylphenidate HCl Extended-Release Capsules CD 10 mg A Medication Guide is required for every prescription dispensed. Please use accompanying Medication Guide. Rx Only 100 Capsules 10 mg label