Methylphenidate Hydrochloride Extended-release Capsules ...

METHYLPHENIDATE HYDROCHLORIDE- methylphenidatehydrochloride capsule, extended release Amneal Pharmaceuticals of New York LLC----------Methylphenidate Hydrochloride Extended-release Capsules, CII (10 mg, 20 mg, 30 mg, 40 mg, 50 mg and 60 mg)Rx only Once Daily

DESCRIPTIONMethylphenidate hydrochloride extended-release capsules are a central nervous system(CNS) stimulant. The extended-release capsules comprise beads each with bothimmediate-release (IR) and extended-release (ER) components such that 30% of thedose is provided by the IR component and 70% of the dose is provided by the ERcomponent. Methylphenidate hydrochloride extended-release capsules are available insix 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 60mg (18 mg IR; 42 mg ER) of methylphenidate hydrochloride for oral administration.Chemically, methylphenidate hydrochloride is d,l (racemic)-threo-methyl α-phenyl-2-piperidineacetate hydrochloride. Its empirical formula is C H NO •HCl. Its structuralformula is:

Methylphenidate hydrochloride, USP is a white, odorless, crystalline powder. Its solutionsare acid to litmus. It is freely soluble in water and in methanol, soluble in alcohol, andslightly soluble in chloroform and in acetone. Its molecular weight is 269.77.Methylphenidate hydrochloride extended-release capsules also contain the following inertingredients: Sugar spheres, povidone, hydroxypropylmethylcellulose and polyethyleneglycol, ethyl cellulose, cetyl alcohol, sodium lauryl sulfate, dibutyl sebacate, gelatin, andtitanium dioxide.The individual capsules contain the following color agents:10 mg capsules: FD&C Blue No. 2, FDA/E172 Yellow Iron Oxide

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20 mg capsules: D&C Red No. 28, FD&C Blue No. 1, FD&C Green No. 330 mg capsules: FDA/E172 Black Iron Oxide, FDA/E172 Red Iron Oxide, FDA/E172 Yellow Iron Oxide40 mg capsules: D&C Yellow No. 10, FD&C Red No. 4050 mg capsules: D&C Red No. 28, FD&C Green No. 3, FDA/E172 Black Iron Oxide

CLINICAL PHARMACOLOGYPharmacodynamicsMethylphenidate hydrochloride is a central nervous system (CNS) stimulant. The modeof therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known.Methylphenidate is thought to block the reuptake of norepinephrine and dopamine intothe presynaptic neuron and increase the release of these monoamines into theextraneuronal 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.PharmacokineticsThe pharmacokinetics of the methylphenidate hydrochloride extended-release capsulemethylphenidate hydrochloride formulation have been studied in healthy adult volunteersand in children with Attention Deficit Hyperactivity Disorder (ADHD).Absorption and DistributionMethylphenidate is readily absorbed. Methylphenidate hydrochloride extended-releasecapsules have a plasma/time concentration profile showing two phases of drug releasewith a sharp, initial slope similar to a methylphenidate immediate-release tablet, and asecond rising portion approximately three hours later, followed by a gradual decline (seeFigure 1 below).Comparison of Immediate Release (IR) and Methylphenidate HydrochlorideExtended-release Capsules Formulations after Repeated Doses ofMethylphenidate Hydrochloride in Children with ADHDMethylphenidate hydrochloride extended-release capsules were administered asrepeated once-daily doses of 20 mg or 40 mg to children aged 7 to 12 years with ADHDfor one week. After a dose of 20 mg, the mean (±SD) early C was 8.6 (±2.2) ng/mL,the later C was 10.9 (±3.9)* ng/mL and AUC was 63.0 (±16.8) ng•h/mL. Thecorresponding values after a 40 mg dose were 16.8 (±5.1) ng/mL, 15.1 (±5.8)* ng/mLand 120 (±39.6) ng•h/mL, respectively. The early peak concentrations (median) werereached 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 and AUCfollowing a dose of 20 mg were slightly lower than those seen with 10 mg of theimmediate-release formulation, dosed at 0 and 4 hours.*25% to 30% of the subjects had only one observed peak (C ) concentration ofmethylphenidate.FIGURE 1: Comparison of Immediate Release (IR) and MethylphenidateHydrochloride Extended-release Capsule Formulations After Repeated Dosesof Methylphenidate Hydrochloride in Children with ADHD

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Dose ProportionalityFollowing single oral doses of 10 mg to 60 mg methylphenidate free base as a solutiongiven to ten healthy male volunteers, C and AUC increased proportionally withincreasing doses. After the 60 mg dose, t was reached 1.5 hours post-dose, with amean C of 31.8 ng/mL (range 24.7 ng/mL to 40.9 ng/mL).Following one week of repeated once-daily doses of 20 mg or 40 mg methylphenidatehydrochloride extended-release capsules to children aged 7 to 12 years with ADHD,C and AUC were proportional to the administered dose.Food EffectsIn a study in adult volunteers to investigate the effects of a high-fat meal on thebioavailability of a dose of 40 mg, the presence of food delayed the early peak byapproximately 1 hour (range -2 to 5 hours delay). The plasma levels rose rapidlyfollowing the food-induced delay in absorption. Overall, a high-fat meal increased theC of methylphenidate hydrochloride extended-release capsules by about 30% andAUC by about 17%, on average (see DOSAGE AND ADMINISTRATION).After a single-dose, the bioavailability (C and AUC) of methylphenidate in 26 healthyadults was unaffected by sprinkling the capsule contents on applesauce as compared tothe intact capsule. This finding demonstrates that a 20 mg methylphenidatehydrochloride extended-release capsule, when opened and sprinkled on one tablespoonof applesauce, is bioequivalent to the intact capsule.Metabolism and ExcretionIn 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 P450isoenzymes, and did not inhibit cytochrome P450 isoenzymes at clinically observedplasma drug concentrations.

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The mean terminal half-life (t ) of methylphenidate following administration ofmethylphenidate hydrochloride extended-release capsules (t =6.8h) is longer than themean terminal (t ) following administration of methylphenidate hydrochloride immediate-release tablets (t =2.9h) and methylphenidate hydrochloride sustained-release tablets(t =3.4h) in healthy adult volunteers. This suggests that the elimination processobserved for methylphenidate hydrochloride extended-release capsules is controlled bythe release rate of methylphenidate from the extended-release formulation, and that thedrug absorption is the rate-limiting process.Alcohol EffectAn in vitro study was conducted to explore the effect of alcohol on the releasecharacteristics of methylphenidate from the methylphenidate hydrochloride extended-release 60 mg capsule dosage form. At an alcohol concentration of 40% there was anincrease in the release rate of methylphenidate in the first hour, resulting in 84% of themethylphenidate being released. The results with the 60 mg capsule are considered tobe representative of the other available capsule strengths. Patients should be advised toavoid alcohol while taking methylphenidate hydrochloride extended-release capsules.Special PopulationsGenderThe pharmacokinetics of methylphenidate after a single-dose of methylphenidatehydrochloride extended-release capsules were similar between adult men and women.RaceThe influence of race on the pharmacokinetics of methylphenidate after methylphenidatehydrochloride extended-release capsules administration has not been studied.AgeThe pharmacokinetics of methylphenidate after methylphenidate hydrochlorideextended-release capsules administration have not been studied in children less than 6years of age.Renal InsufficiencyThere is no experience with the use of methylphenidate hydrochloride extended-releasecapsules in patients with renal insufficiency. After oral administration of radiolabeledmethylphenidate in humans, methylphenidate was extensively metabolized andapproximately 80% of the radioactivity was excreted in the urine in the form of ritalinicacid. Since renal clearance is not an important route of methylphenidate clearance, renalinsufficiency is expected to have little effect on the pharmacokinetics of methylphenidatehydrochloride extended-release capsules.Hepatic InsufficiencyThere is no experience with the use of methylphenidate hydrochloride extended-releasecapsules in patients with hepatic insufficiency.

CLINICAL STUDIESMethylphenidate hydrochloride extended-release capsules were evaluated in a double-blind, parallel-group, placebo-controlled trial in which 321 untreated or previously treated

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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-impulsivesubtype of ADHD; patients with the predominantly inattentive subtype were excluded.Patients randomized to the methylphenidate hydrochloride extended-release capsulesgroup received 20 mg daily for the first week. Their dosage could be increased weekly toa 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 andagain in the afternoon on three alternate days of each treatment week. The change frombaseline of the overall average (i.e. an average of morning and afternoon scores over 3days) of the total TCGIS scores during the last week of treatment was analyzed as theprimary efficacy parameter. Patients treated with methylphenidate hydrochlorideextended-release capsules showed a statistically significant improvement in symptomscores from baseline over patients who received placebo (see Figure 2). Separateanalyses of TCGIS scores in the morning and afternoon revealed superiority inimprovement with methylphenidate hydrochloride extended-release capsules overplacebo during both time periods (see Figure 3). This demonstrates that a singlemorning dose of methylphenidate hydrochloride extended-release capsules exerts atreatment effect in both the morning and the afternoon.

INDICATION AND USAGEAttention Deficit Hyperactivity Disorder (ADHD)Methylphenidate hydrochloride extended-release capsules are indicated for the

treatment of Attention Deficit Hyperactivity Disorder (ADHD).The efficacy of methylphenidate hydrochloride extended-release capsules in thetreatment of ADHD was established in one controlled trial of children aged 6 to 15 whomet DSM-IV criteria for ADHD (see CLINICAL PHARMACOLOGY).A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies thepresence of hyperactive-impulsive or inattentive symptoms that caused impairment andwere present before age 7 years. The symptoms must cause clinically significantimpairment, e.g., in social, academic, or occupational functioning, and be present in twoor more settings, e.g., school (or work) and at home. The symptoms must not be betteraccounted for by another mental disorder. For the Inattentive Type, at least six of thefollowing symptoms must have persisted for at least 6 months: lack of attention todetails/careless mistakes; lack of sustained attention; poor listener; failure to followthrough on tasks; poor organization; avoids tasks requiring sustained mental effort;loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least sixof the following symptoms must have persisted for at least 6 months:fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quietactivities; “on the go;” excessive talking; blurting answers; can’t wait turn; intrusive. TheCombined Types requires both inattentive and hyperactive-impulsive criteria to be met.Special Diagnostic ConsiderationsSpecific 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 diagnosismust be based upon a complete history and evaluation of the child and not solely on thepresence of the required number of DSM-IV characteristics.Need For Comprehensive Treatment ProgramMethylphenidate hydrochloride extended-release capsules are indicated as an integralpart of a total treatment program for ADHD that may include other measures(psychological, educational, social) for patients with this syndrome. Drug treatment maynot be indicated for all children with this syndrome. Stimulants are not intended for usein the child who exhibits symptoms secondary to environmental factors and/or otherprimary psychiatric disorders, including psychosis. Appropriate educational placement isessential and psychosocial intervention is often helpful. When remedial measures aloneare insufficient, the decision to prescribe stimulant medication will depend upon thephysician’s assessment of the chronicity and severity of the child’s symptoms.Long-Term UseThe effectiveness of methylphenidate hydrochloride extended-release capsules for long-term use, i.e. for more than 3 weeks, has not been systematically evaluated in controlledtrials. Therefore, the physician who elects to use methylphenidate hydrochlorideextended-release capsules for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see DOSAGE ANDADMINISTRATION).

CONTRAINDICATIONSAgitation

Methylphenidate hydrochloride extended-release capsules are contraindicated in patientswith marked anxiety, tension and agitation, since the drug may aggravate thesesymptoms.Hypersensitivity to Methylphenidate or Other ExcipientsMethylphenidate hydrochloride extended-release capsules are contraindicated in patientsknown to be hypersensitive to methylphenidate or other components of the product.Methylphenidate hydrochloride extended-release capsules contain sucrose. Therefore,patients with rare hereditary problems of fructose intolerance, glucose-galactosemalabsorption, or sucrase-isomaltase insufficiency should not take this medicine.GlaucomaMethylphenidate hydrochloride extended-release capsules are contraindicated in patientswith glaucoma.TicsMethylphenidate hydrochloride extended-release capsules are contraindicated in patientswith motor tics or with a family history or diagnosis of Tourette’s syndrome (seeADVERSE REACTIONS).Monoamine Oxidase InhibitorsMethylphenidate hydrochloride extended-release capsules are contraindicated duringtreatment with monoamine oxidase inhibitors, and also within a minimum of 14 daysfollowing discontinuation of a monoamine oxidase inhibitor (hypertensive crises mayresult).Hypertension and Other Cardiovascular ConditionsMethylphenidate hydrochloride extended-release capsules are contraindicated in patientswith severe hypertension, angina pectoris, cardiac arrhythmias, heart failure, recentmyocardial infarction, hyperthyroidism or thyrotoxicosis (see WARNINGS).Halogenated AnestheticsThere is a risk of sudden blood pressure increase during surgery. If surgery is planned,methylphenidate hydrochloride extended-release capsules should not be taken on theday of the surgery.

WARNINGSSerious Cardiovascular EventsSudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious HeartProblemsChildren and Adolescents

Sudden death has been reported in association with CNS stimulant treatment at usualdoses in children and adolescents with structural cardiac abnormalities or other seriousheart problems. Although some serious heart problems alone carry an increased risk ofsudden death, stimulant products generally should not be used in children oradolescents with known serious structural cardiac abnormalities, cardiomyopathy,

serious heart rhythm abnormalities, or other serious cardiac problems that may placethem at increased vulnerability to the sympathomimetic effects of a stimulant drug (seeCONTRAINDICATIONS).Adults

Sudden deaths, stroke, and myocardial infarction have been reported in adults takingstimulant drugs at usual doses for ADHD. Although the role of stimulants in these adultcases is also unknown, adults have a greater likelihood than children of having seriousstructural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities,coronary artery disease, or other serious cardiac problems. Adults with suchabnormalities should also generally not be treated with stimulant drugs (seeCONTRAINDICATIONS).Hypertension and Other Cardiovascular ConditionsStimulant medications cause a modest increase in average blood pressure (about 2mmHg to 4 mmHg) and average heart rate (about 3 bpm to 6 bpm), and individuals mayhave larger increases. While the mean changes alone would not be expected to haveshort-term consequences, all patients should be monitored for larger changes in heartrate and blood pressure. Caution is indicated in treating patients whose underlyingmedical conditions might be compromised by increases in blood pressure or heart rate,e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, orventricular arrhythmia (see CONTRAINDICATIONS).Assessing Cardiovascular Status in Patients Being Treated with StimulantMedicationsChildren, adolescents, or adults who are being considered for treatment with stimulantmedications should have a careful history (including assessment for a family history ofsudden death or ventricular arrhythmia) and physical exam to assess for the presenceof cardiac disease, and should receive further cardiac evaluation if findings suggest suchdisease (e.g., electrocardiogram and echocardiogram). Patients who develop symptomssuch as exertional chest pain, unexplained syncope, or other symptoms suggestive ofcardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.Psychiatric Adverse EventsPre-Existing PsychosisAdministration of stimulants may exacerbate symptoms of behavior disturbance andthought disorder in patients with a pre-existing psychotic disorder.Bipolar IllnessParticular care should be taken in using stimulants to treat ADHD in patients withcomorbid bipolar disorder because of concern for possible induction of a mixed/manicepisode in such patients. Prior to initiating treatment with a stimulant, patients withcomorbid depressive symptoms should be adequately screened to determine if they areat risk for bipolar disorder; such screening should include a detailed psychiatric history,including a family history of suicide, bipolar disorder, and depression.Emergence of New Psychotic or Manic SymptomsTreatment emergent psychotic or manic symptoms, e.g., hallucinations, delusionalthinking, or mania in children and adolescents without prior history of psychotic illness

or mania can be caused by stimulants at usual doses. If such symptoms occur,consideration should be given to a possible causal role of the stimulant, anddiscontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patientswith events out of 3,482 exposed to methylphenidate or amphetamine for several weeksat usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.AggressionAggressive behavior or hostility is often observed in children and adolescents withADHD, and has been reported in clinical trials and the postmarketing experience of somemedications indicated for the treatment of ADHD. Although there is no systematicevidence that stimulants cause aggressive behavior or hostility, patients beginningtreatment for ADHD should be monitored for the appearance of or worsening ofaggressive behavior or hostility.Long-Term Suppression of GrowthCareful follow-up of weight and height in children ages 7 to 10 years who wererandomized to either methylphenidate or non-medication treatment groups over 14months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggeststhat consistently medicated children (i.e. treatment for 7 days per week throughout theyear) have a temporary slowing in growth rate (on average, a total of about 2 cm lessgrowth in height and 2.7 kg less growth in weight over 3 years), without evidence ofgrowth rebound during this period of development. Published data are inadequate todetermine whether chronic use of amphetamines may cause a similar suppression ofgrowth, however, it is anticipated that they likely have this effect as well. Therefore,growth should be monitored during treatment with stimulants, and patients who are notgrowing or gaining height or weight as expected may need to have their treatmentinterrupted.SeizuresThere is some clinical evidence that stimulants may lower the convulsive threshold inpatients with prior history of seizures, in patients with prior EEG abnormalities inabsence of seizures, and, very rarely, in patients without a history of seizures and noprior EEG evidence of seizures. In the presence of seizures, the drug should bediscontinued.PriapismProlonged and painful erections, sometimes requiring surgical intervention, have beenreported with methylphenidate products in both pediatric and adult patients. Priapismwas not reported with drug initiation but developed after some time on the drug, oftensubsequent to an increase in dose. Priapism has also appeared during a period of drugwithdrawal (drug holidays or discontinuation). Patients who develop abnormallysustained or frequent and painful erections should seek immediate medical attention.Peripheral Vasculopathy, including Raynaud’s phenomenonStimulants, including methylphenidate hydrochloride extended-release capsules, used totreat ADHD are associated with peripheral vasculopathy, including Raynaud’sphenomenon. Signs and symptoms are usually intermittent and mild; however, very raresequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral

vasculopathy, including Raynaud’s phenomenon, were observed in post-marketingreports at different times and at therapeutic doses in all age groups throughout thecourse of treatment. Signs and symptoms generally improve after reduction in dose ordiscontinuation of drug. Careful observation for digital changes is necessary duringtreatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral)may be appropriate for certain patients.Visual DisturbanceDifficulties with accommodation and blurring of vision have been reported with stimulanttreatment.Use in Children Under Six Years of AgeMethylphenidate hydrochloride extended-release capsules should not be used in childrenunder six years, since safety and efficacy in this age group have not been established.

Drug DependenceMethylphenidate hydrochloride extended-release capsules should be given cautiously topatients with a history of drug dependence or alcoholism. Chronic abusive use can leadto marked tolerance and psychological dependence with varying degrees of abnormalbehavior. Frank psychotic episodes can occur, especially with parenteral abuse. Carefulsupervision is required during withdrawal from abusive use since severe depressionmay occur. Withdrawal following chronic therapeutic use may unmask symptoms of theunderlying disorder that may require follow-up.

PRECAUTIONSHematologic MonitoringPeriodic CBC, differential, and platelet counts are advised during prolonged therapy.Drug TestingMethylphenidate hydrochloride extended-release capsules contain methylphenidatewhich may result in a positive result during drug testing.

Information for PatientsPatients should be instructed to take one dose in the morning before breakfast. Thepatients 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. Thecapsules and the capsule contents must not be crushed or chewed.Patients should be advised to avoid alcohol while taking methylphenidate hydrochlorideextended-release capsules. Consumption of alcohol while taking methylphenidatehydrochloride extended-release capsules may result in a more rapid release of the doseof methylphenidate.Priapism

Advise patients, caregivers, and family members of the possibility of painful or prolongedpenile erections (priapism). Instruct the patient to seek immediate medicalattention in the event of priapism.Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’sphenomenon]

Instruct patients beginning treatment with methylphenidate hydrochloride extended-release capsules about the risk of peripheral vasculopathy, including Raynaud’sPhenomenon, 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 colorchange, or sensitivity to temperature in fingers or toes.Instruct patients to call their physician immediately with any signs ofunexplained wounds appearing on fingers or toes while takingmethylphenidate hydrochloride extended-release capsules.Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certainpatients.

Prescribers or other health professionals should inform patients, their families, and theircaregivers about the benefits and risks associated with treatment with methylphenidateand should counsel them in its appropriate use. A patient Medication Guide is availablefor methylphenidate hydrochloride extended-release capsules. The prescriber orhealthcare professional should instruct patients, their families, and their caregivers toread the Medication Guide and should assist them in understanding its contents.Patients should be given the opportunity to discuss the contents of the Medication Guideand to obtain answers to any questions they may have. The complete text of theMedication Guide is reprinted at the end of this document. The Medication Guide mayalso be found in the full prescribing information for methylphenidate hydrochlorideextended-release capsules on www.amneal.com or by calling 1-877-835-5472.Drug InteractionsBecause of possible effects on blood pressure, methylphenidate hydrochlorideextended-release capsules should be used cautiously with pressor agents.Human pharmacologic studies have shown that methylphenidate may inhibit themetabolism of coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin,primidone), phenylbutazone and some antidepressants (tricyclics and selective serotoninreuptake inhibitors). Downward dose adjustment of these drugs may be required whengiven concomitantly with methylphenidate. It may be necessary to adjust the dosageand monitor plasma drug concentrations (or, in the case of coumarin, coagulationtimes), when initiating or discontinuing concomitant methylphenidate.In theory, there is a possibility that the clearance of methylphenidate might be affectedby urinary pH, either being increased with acidifying agents or decreased with alkalizingagents. This should be considered when methylphenidate is given in combination withagents that alter urinary pH.Halogenated AnestheticsThere is a risk of sudden blood pressure increase during surgery. If surgery is planned,methylphenidate hydrochloride extended-release capsules should not be taken the dayof the surgery.

Carcinogenesis, Mutagenesis, and Impairment of FertilityIn a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate causedan increase in hepatocellular adenomas and, in males only, an increase inhepatoblastomas, at a daily dose of approximately 60 mg/kg/day. This dose isapproximately 30 times and 4 times the maximum recommended human dose ofmethylphenidate hydrochloride extended-release capsules on a mg/kg and mg/m basis,respectively. Hepatoblastoma is a relatively rare rodent malignant tumor type. There wasno increase in total malignant hepatic tumors. The mouse strain used is sensitive to thedevelopment of hepatic tumors, and the significance of these results to humans isunknown.Methylphenidate did not cause any increases in tumors in a lifetime carcinogenicity studycarried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, whichis approximately 22 times and 5 times the maximum recommended human dose ofmethylphenidate hydrochloride extended-release capsules on a mg/kg and mg/m basis,respectively.In a 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which issensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male andfemale mice were fed diets containing the same concentration of methylphenidate as inthe lifetime carcinogenicity study; the high-dose groups were exposed to 60 to 74mg/kg/day of methylphenidate.Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or inthe in vitro mouse lymphoma cell forward mutation assay. Sister chromatid exchangesand chromosome aberrations were increased, indicative of a weak clastogenic response,in an in vitro assay in cultured Chinese Hamster Ovary cells. Methylphenidate wasnegative 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 dietscontaining the drug in an 18-week Continuous Breeding study. The study wasconducted at doses up to 160 mg/kg/day, approximately 80-fold and 8-fold the highestrecommended human dose of methylphenidate hydrochloride extended-releasecapsules on a mg/kg and mg/m basis, respectively.PregnancyTeratogenic EffectsPregnancy Category C

Methylphenidate has been shown to have teratogenic effects in rabbits when given indoses of 200 mg/kg/day, which is approximately 100 times and 40 times the maximumrecommended human dose on a mg/kg and mg/m basis, respectively.A reproduction study in rats revealed no evidence of teratogenicity at an oral dose of 58mg/kg/day. However, this dose, which caused some maternal toxicity, resulted indecreased postnatal pup weights and survival when given to the dams from day one ofgestation through the lactation period. This dose is approximately 30 fold and 6 fold themaximum recommended human dose of methylphenidate hydrochloride extended-release capsules on a mg/kg and mg/m basis, respectively.There are no adequate and well-controlled studies in pregnant women. Methylphenidatehydrochloride extended-release capsules should be used during pregnancy only if the

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potential benefit justifies the potential risk to the fetus.Nursing MothersIt is not known whether methylphenidate is excreted in human milk. Because manydrugs are excreted in human milk, caution should be exercised if methylphenidatehydrochloride extended-release capsules are administered to a nursing woman.Pediatric UseThe safety and efficacy of methylphenidate hydrochloride extended-release capsules inchildren under 6 years old have not been established. Long-term effects ofmethylphenidate in children have not been well established (see WARNINGS).

ADVERSE REACTIONSThe premarketing development program for methylphenidate hydrochloride extended-release capsules included exposures in a total of 228 participants in clinical trials (188pediatric patients with ADHD, 40 healthy adult subjects). These participants receivedmethylphenidate hydrochloride extended-release capsules 20, 40, and/or 60 mg/day.The 188 patients (ages 6 to 15) were evaluated in one controlled clinical study, onecontrolled, crossover clinical study, and one uncontrolled clinical study. Safety data on allpatients are included in the discussion that follows. Adverse reactions were assessed bycollecting adverse events, results of physical examinations, vital signs, weights,laboratory analyses, and ECGs.Adverse events during exposure were obtained primarily by general inquiry andrecorded by clinical investigators using terminology of their own choosing.Consequently, it is not possible to provide a meaningful estimate of the proportion ofindividuals experiencing adverse events without first grouping similar types of eventsinto a smaller number of standardized event categories. In the tables and listings thatfollow, COSTART terminology has been used to classify reported adverse events.The stated frequencies of adverse events represent the proportion of individuals whoexperienced, at least once, a treatment-emergent adverse event of the type listed. Anevent was considered treatment emergent if it occurred for the first time or worsenedwhile receiving therapy following baseline evaluation.Adverse Findings in Clinical Trials with Methylphenidate HydrochlorideExtended-release CapsulesAdverse Events Associated with Discontinuation of TreatmentIn the 3-week placebo-controlled, parallel-group trial, two methylphenidate hydrochlorideextended-release capsules-treated patients (1%) and no placebo-treated patientsdiscontinued due to an adverse event (rash and pruritus; and headache, abdominal pain,and dizziness, respectively).Adverse Events Occurring at an Incidence of 5% or more amongMethylphenidate Hydrochloride Extended-release Capsules-Treated PatientsTable 1 enumerates, for a pool of the three studies in pediatric patients with ADHD, atmethylphenidate hydrochloride extended-release capsules doses of 20, 40, or 60mg/day, the incidence of treatment-emergent adverse events. One study was a 3-weekplacebo-controlled, parallel-group trial, one study was a controlled, crossover trial, and

the third study was an open titration trial. The table includes only those events thatoccurred in 5% or more of patients treated with methylphenidate hydrochlorideextended-release capsules where the incidence in patients treated with methylphenidatehydrochloride extended-release capsules was greater than the incidence in placebo-treated patients.The prescriber should be aware that these figures cannot be used to predict theincidence of adverse events in the course of usual medical practice where patientcharacteristics and other factors differ from those which prevailed in the clinical trials.Similarly, the cited frequencies cannot be compared with figures obtained from otherclinical investigations involving different treatments, uses, and investigators. The citedfigures, however, do provide the prescribing physician with some basis for estimatingthe relative contribution of drug and non-drug factors to the adverse event incidencerate in the population studied.TABLE 1: Incidence of Treatment-Emergent Events in a Pool of 3 to 4 WeekClinical Trials of Methylphenidate Hydrochloride Extended-release Capsules

Body System Preferred Term

MethylphenidateHydrochlorideExtended-releaseCapsules(n=188)

Placebo(n=190)

GeneralHeadacheAbdominal pain(stomach ache)

12%7%

8%4%

Digestive System Anorexia (loss ofappetite) 9% 2%

Nervous System Insomnia 5% 2%: Events, regardless of causality, for which the incidence for patients treated with

methylphenidate hydrochloride extended-release capsules were at least 5% and greaterthan the incidence among placebo-treated patients. Incidence has been rounded to thenearest whole number.

Adverse Events with Other Marketed Methylphenidate HydrochlorideProductsNervousness and insomnia are the most common adverse reactions reported with othermethylphenidate products. Other reactions include hypersensitivity (including skin rash,urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme withhistopathological findings of necrotizing vasculitis, and thrombocytopenic purpura);anorexia; nausea; dizziness; palpitations; headache; dyskinesia; drowsiness; bloodpressure and pulse changes, both up and down; tachycardia; angina; cardiacarrhythmia; abdominal pain; weight loss during prolonged therapy. There have been rarereports of Tourette’s Syndrome and obsessive-compulsive disorder. Toxic psychosishas been reported. Although a definite causal relationship has not been established, thefollowing have been reported in patients taking this drug: instances of abnormal liverfunction, ranging from transaminase elevation to severe hepatic injury; isolated cases ofcerebral arteritis and/or occlusion; leucopenia and/or anemia; transient depressed mood;a few instances of scalp hair loss. Very rare reports of neuroleptic malignant syndrome

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(NMS) have been reported, and, in most of these, patients were concurrently receivingtherapies associated with NMS. In a single report, a ten year old boy who had beentaking methylphenidate for approximately 18 months experienced an NMS-like eventwithin 45 minutes of ingesting his first dose of venlafaxine. It is uncertain whether thiscase represented a drug-drug interaction, a response to either drug alone, or someother cause.In children, loss of appetite, abdominal pain, weight loss during prolonged therapy,insomnia and tachycardia may occur more frequently; however, any of the otheradverse reactions listed above may also occur.Postmarketing ExperienceIn addition to the adverse events listed above, the following have been reported inpatients receiving methylphenidate hydrochloride extended-release capsules worldwide.The list is alphabetized: abnormal behavior, aggression, anxiety, bruxism, cardiac arrest,depression, fixed drug eruption, hyperactivity, irritability, libido changes, migraine,obsessive-compulsive disorder, peripheral coldness, Raynaud’s phenomenon, reversibleischaemic neurological deficit, rhabdomyolysis, serotonin syndrome in combination withserotonergic drugs, sudden death, suicidal behavior (including completed suicide), andthrombocytopenia. Data are insufficient to support an estimation of incidence orestablish causation.To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticalsat 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG ABUSE AND DEPENDENCEControlled Substance ClassMethylphenidate hydrochloride extended-release capsules, like other methylphenidateproducts, are classified as a Schedule II controlled substance by federal regulation.Abuse, Dependence, and ToleranceSee WARNINGS for boxed warning containing drug abuse and dependenceinformation.

OVERDOSAGESigns and SymptomsSigns and symptoms of acute methylphenidate overdosage, resulting principally fromoverstimulation of the CNS and from excessive sympathomimetic effects, may includethe following: vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions(may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating,flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias,hypertension, mydriasis, dryness of mucous membranes, and rhabdomyolysis.Recommended TreatmentTreatment consists of appropriate supportive measures. The patient must be protected

against self-injury and against external stimuli that would aggravate overstimulationalready present. Gastric contents may be evacuated by gastric lavage as indicated.Before performing gastric lavage, control agitation and seizures if present and protectthe airway. Other measures to detoxify the gut include administration of activatedcharcoal and a cathartic. Intensive care must be provided to maintain adequatecirculation and respiratory exchange; external cooling procedures may be required forhyperpyrexia.Efficacy of peritoneal dialysis or extracorporeal hemodialysis for methylphenidatehydrochloride extended-release capsules overdosage has not been established.The prolonged release of methylphenidate from methylphenidate hydrochlorideextended-release capsules should be considered when treating patients with overdose.Poison Control CenterAs with the management of all overdosage, the possibility of multiple drug ingestionshould be considered. The physician may wish to consider contacting a poison controlcenter for up-to-date information on the management of overdosage withmethylphenidate.

DOSAGE AND ADMINISTRATIONMethylphenidate hydrochloride extended-release capsules are administered once daily inthe morning, before breakfast.Methylphenidate hydrochloride extended-release capsules may be swallowed whole withthe aid of liquids, or alternatively, the capsule may be opened and the capsule contentssprinkled onto a small amount (tablespoon) of applesauce and given immediately, andnot stored for future use. Drinking some fluids, e.g., water, should follow the intake ofthe sprinkles with applesauce. The capsules and the capsule contents must not becrushed or chewed (see PRECAUTIONS: Information for Patients). Patients shouldbe advised to avoid alcohol while taking methylphenidate hydrochloride extended-releasecapsules.Dosage should be individualized according to the needs and responses of the patient.Initial TreatmentThe recommended starting dose of methylphenidate hydrochloride extended-releasecapsules is 20 mg once daily. Dosage may be adjusted in weekly 10 mg to 20 mgincrements to a maximum of 60 mg/day taken once daily in the morning, dependingupon tolerability and degree of efficacy observed. Daily dosage above 60 mg is notrecommended.Maintenance/Extended TreatmentThere is no body of evidence available from controlled trials to indicate how long thepatient with ADHD should be treated with methylphenidate hydrochloride extended-release capsules. It is generally agreed, however, that pharmacological treatment ofADHD may be needed for extended periods. Nevertheless, the physician who elects touse methylphenidate hydrochloride extended-release capsules for extended periods inpatients with ADHD should periodically re-evaluate the long-term usefulness of the drugfor the individual patient with trials off medication to assess the patient’s functioning

without pharmacotherapy. Improvement may be sustained when the drug is eithertemporarily or permanently discontinued.Dose Reduction and DiscontinuationIf paradoxical aggravation of symptoms or other adverse events occur, the dosageshould be reduced, or, if necessary, the drug should be discontinued.If improvement is not observed after appropriate dosage adjustment over a one-monthperiod, the drug should be discontinued.

HOW SUPPLIEDMethylphenidate Hydrochloride Extended-release Capsules are available in six strengths.Methylphenidate Hydrochloride Extended-release Capsules, 10 mg are green cap andwhite body, opaque capsules, imprinted with CP over 401 on the cap and 10 mg on thebody.They are available as:Bottles of 100: NDC 0115-1736-01Methylphenidate Hydrochloride Extended-release Capsules, 20 mg are blue cap andwhite body, opaque capsules, imprinted with CP over 402 on the cap and 20 mg on thebody.They are available as:Bottles of 100: NDC 0115-1737-01Methylphenidate Hydrochloride Extended-release Capsules, 30 mg are brown cap andwhite body, opaque capsules, imprinted with CP over 403 on the cap and 30 mg on thebody.They are available as:Bottles of 100: NDC 0115-1738-01Methylphenidate Hydrochloride Extended-release Capsules, 40 mg are yellow cap andwhite body, opaque capsules, imprinted with CP over 404 on the cap and 40 mg on thebody.They are available as:Bottles of 100: NDC 0115-1739-01Methylphenidate Hydrochloride Extended-release Capsules, 50 mg are navy blue capand white body, opaque capsules, imprinted with CP over 405 on the cap and 50 mgon the body.They are available as:Bottles of 100: NDC 0115-1740-01Methylphenidate Hydrochloride Extended-release Capsules, 60 mg are white, opaquecapsule imprinted with CP over 406 on the cap and 60 mg on the body.They are available as: Bottles of 100: NDC 0115-1741-01Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to

86°F) [see USP Controlled Room Temperature].Keep out of the reach of children.

REFERENCEAmerican Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.

American Psychiatric Association 1994. 4th ed. Washington D.C.For additional copies of the printed Medication Guide, please visit www.amneal.com orcall 1-877-835-5472.Manufactured by:Amneal Pharmaceuticals of New York, LLCBrookhaven, NY 11719Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807Rev. 12-2021-01

MEDICATION GUIDEMethylphenidate Hydrochloride (meth" il fen' i date hye" droe klor' ide) Extended-release Capsules, CIIRead the Medication Guide that comes with methylphenidate hydrochloride extended-release capsules 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 talkingto your doctor about your or your child’s treatment with methylphenidate hydrochlorideextended-release capsules.

What is the most important information I should know aboutmethylphenidate hydrochloride extended-release capsules?

The following have been reported with use of methylphenidate hydrochlorideand other stimulant medicines.

1. Heart-related problems:sudden death in patients who have heart problems or heart defectsstroke and heart attack in adultsincreased blood pressure and heart rate

Tell your doctor if you or your child has any heart problems, heart defects, high bloodpressure, or a family history of these problems.

Your doctor should check you or your child carefully for heart problems before startingmethylphenidate hydrochloride extended-release capsules.

Your doctor should check your or your child’s blood pressure and heart rate regularlyduring treatment with methylphenidate hydrochloride extended-release capsules.

Call your doctor right away if you or your child has any signs of heartproblems such as chest pain, shortness of breath, or fainting while takingmethylphenidate hydrochloride extended-release capsules.

2. Mental (Psychiatric) problems: All Patients

new or worse behavior and thought problemsnew or worse bipolar illnessnew or worse aggressive behavior or hostility

Children and Teenagersnew psychotic symptoms (such as hearing voices, believing things thatare not true, are suspicious) or new manic symptoms

Tell your doctor about any mental problems you or your child have, or about a familyhistory of suicide, bipolar illness, or depression.

Call your doctor right away if you or your child has any new or worseningmental symptoms or problems while taking methylphenidate hydrochlorideextended-release capsules, especially seeing or hearing things that are notreal, believing things that are not real, or are suspicious.

3. Circulation Problems in fingers and toes (Peripheral vasculopathy, includingRaynaud’s phenomenon): fingers or toes may feel numb, cool, painful, and/or maychange color from pale, to blue, to red

Tell your doctor if you have or your child has numbness, pain, skin color change, orsensitivity to temperature in your fingers or toes.Call your doctor right away if you have or your child has any signs ofunexplained wounds appearing on fingers or toes while takingmethylphenidate hydrochloride extended-release capsules.

What are methylphenidate hydrochloride extended-release capsules?Methylphenidate hydrochloride extended-release capsules are a central nervous systemstimulant prescription medicine. It is used for the treatment of Attention-DeficitHyperactivity Disorder (ADHD).Methylphenidate hydrochloride extended-release capsules may help increase attentionand decrease impulsiveness and hyperactivity in patients with ADHD.Methylphenidate hydrochloride extended-release capsules should be used as a part of atotal treatment program for ADHD that may include counseling or other therapies.

Methylphenidate hydrochloride extended-release capsules are a federallycontrolled substance (CII) because it can be abused or lead to dependence.Keep methylphenidate hydrochloride extended-release capsules in a safe

place to prevent misuse and abuse. Selling or giving away methylphenidatehydrochloride extended-release capsules may harm others, and is againstthe law.Tell your doctor if you or your child have (or have a family history of) ever abused orbeen dependent on alcohol, prescription medicines or street drugs.

Who should not take methylphenidate hydrochloride extended-releasecapsules?Methylphenidate hydrochloride extended-release capsules should not betaken if you or your child:

are very anxious, tense, or agitatedhave an eye problem called glaucomahave Tics or Tourette’s syndrome, or a family history of Tourette’s syndrome. Ticsare hard to control repeated movements or sounds.have severe high blood pressure or a heart problemhave hyperthyroidismare taking or have taken within the past 14 days an antidepression medicine called amonoamine oxidase inhibitor or MAOI.are allergic to anything in methylphenidate hydrochloride extended-release capsules.See the end of this Medication Guide for a complete list of ingredients.

Methylphenidate hydrochloride extended-release capsules should not be used in childrenless than 6 years old because it has not been studied in this age group.Methylphenidate hydrochloride extended-release capsules may not be rightfor you or your child. Before starting methylphenidate hydrochlorideextended-release capsules tell your or your child’s doctor about all healthconditions (or a family history of) including:

heart problems, heart defects, high blood pressuremental problems including psychosis, mania, bipolar illness, or depressionTics or Tourette’s syndromeseizures or have had an abnormal brain wave test (EEG)circulation problem in fingers and toes

Tell your doctor if you or your child is pregnant, planning to become pregnant, orbreastfeeding.Can methylphenidate hydrochloride extended-release capsules be taken withother medicines?Tell your doctor about all of the medicines that you or your child takesincluding prescription and non-prescription medicines, vitamins, and herbalsupplements. Methylphenidate hydrochloride extended-release capsules and somemedicines may interact with each other and cause serious side effects. Sometimes thedoses of other medicines will need to be adjusted while taking methylphenidatehydrochloride extended-release capsules.Your doctor will decide whether methylphenidate hydrochloride extended-releasecapsules can be taken with other medicines.Especially tell your doctor if you or your child takes:

anti-depression medicines including MAOIsseizure medicinesblood thinner medicinesblood pressure medicinescold or allergy medicines that contain decongestants

Know the medicines that you or your child takes. Keep a list of your medicines with youto show your doctor and pharmacist.Do not start any new medicine while taking methylphenidate hydrochlorideextended-release capsules without talking to your doctor first.How should methylphenidate hydrochloride extended-release capsules betaken?

Take methylphenidate hydrochloride extended-release capsules exactly asprescribed. Your doctor may adjust the dose until it is right for you or your child.Take methylphenidate hydrochloride extended-release capsules once each day in themorning before breakfast. Methylphenidate hydrochloride extended-releasecapsules are an extended release capsule. It releases medicine into your bodythroughout the day.Methylphenidate hydrochloride extended-release capsules can be taken with orwithout food.Swallow methylphenidate hydrochloride extended-release capsules whole with wateror other liquids. If you cannot swallow the capsule, open it and sprinkle the medicineover a spoonful of applesauce. Swallow the applesauce and medicine mixture withoutchewing. Follow with a drink of water or other liquid. Never chew or crush thecapsule or the medicine inside the capsule.Methylphenidate hydrochloride extended-release capsules should not be taken withalcohol. This may result in a more rapid release of the dose of methylphenidatehydrochloride extended-release capsules.From time to time, your doctor may stop methylphenidate hydrochloride extended-release capsules treatment for a while to check ADHD symptoms.Your doctor may do regular checks of the blood, heart, and blood pressure whiletaking methylphenidate hydrochloride extended-release capsules. Children shouldhave their height and weight checked often while taking methylphenidatehydrochloride extended-release capsules. Methylphenidate hydrochloride extended-release capsules treatment may be stopped if a problem is found during these check-ups.If you or your child takes too much methylphenidate hydrochlorideextended-release capsules or overdoses, call your doctor or poisoncontrol center right away, or get emergency treatment.

What are possible side effects of methylphenidate hydrochloride extended-release capsules?See “What is the most important information I should know aboutmethylphenidate hydrochloride extended-release capsules?” for information onreported heart and mental problems.Other serious side effects include:

slowing of growth (height and weight) in children

seizures, mainly in patients with a history of seizureseyesight changes or blurred visionPainful and prolonged erections (priapism) have occurred with methylphenidate. Ifyou or your child develops priapism, seek medical help right away. Because of thepotential for lasting damage, priapism should be evaluated by a doctor immediately.

Common side effects include:headachedecreased appetitestomach achenervousnesstrouble sleepingdizziness

Talk to your doctor if you or your child has side effects that are bothersome or do notgo away.This is not a complete list of possible side effects. Ask your doctor or pharmacist formore information.Call your doctor for medical advice about side effects. You may report sideeffects to FDA at 1-800-FDA-1088.How should I store methylphenidate hydrochloride extended-releasecapsules?

Store methylphenidate hydrochloride extended-release capsules in a safe place atroom temperature, 59° to 86°F (15° to 30°C). Protect from moisture.Keep methylphenidate hydrochloride extended-release capsules and allmedicines out of the reach of children.

General information about methylphenidate hydrochloride extended-releasecapsulesMedicines are sometimes prescribed for purposes other than those listed in a MedicationGuide. Do not use methylphenidate hydrochloride extended-release capsules for acondition for which it was not prescribed. Do not give methylphenidate hydrochlorideextended-release capsules to other people, even if they have the same condition. It mayharm them and it is against the law.This Medication Guide summarizes the most important information aboutmethylphenidate hydrochloride extended-release capsules. If you would like moreinformation, talk with your doctor. You can ask your doctor or pharmacist forinformation about methylphenidate hydrochloride extended-release capsules that waswritten for healthcare professionals. For more information about methylphenidatehydrochloride extended-release capsules call 1-877-835-5472.What are the ingredients in methylphenidate hydrochloride extended-releasecapsules?Active Ingredient: methylphenidate hydrochloride, USPInactive Ingredients: sugar spheres, povidone, hydroxypropylmethylcellulose andpolyethylene glycol, ethyl cellulose, cetyl alcohol, sodium lauryl sulfate, dibutyl sebacate,gelatin, and titanium dioxide.

The individual capsules contain the following coloring agents:10 mg capsules: FD&C Blue No. 2, FDA/E172 Yellow Iron Oxide20 mg capsules: D&C Red No. 28, FD&C Blue No. 1, FD&C Green No. 330 mg capsules: FDA/E172 Black Iron Oxide, FDA/E172 Red Iron Oxide, FDA/E172 Yellow Iron Oxide40 mg capsules: D&C Yellow No. 10, FD&C Red No. 4050 mg capsules: D&C Red No. 28, FD&C Green No. 3, FDA/E172 Black Iron OxideThis Medication Guide has been approved by the U.S. Food and DrugAdministration.For additional copies of the printed Medication Guide, please visit www.amneal.com orcall 1-877-835-5472.Manufactured by:Amneal Pharmaceuticals of New York, LLCBrookhaven, NY 11719Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807Rev. 12-2021-01Dispense with Medication Guide available at:documents.amneal.com/mg/methylphenidate-hcl-er-cap.pdf

PRINCIPAL DISPLAY PANEL - 10 mgNDC 0115-1736-01Methylphenidate Hydrochloride Extended-Release Capsules, 10 mg (CII)Rx only100 Capsules



PRINCIPAL DISPLAY PANEL - 40 mgNDC 0115-1739-01Methylphenidate Hydrochloride Extended-Release Capsules, 40 mg (CII)

Rx only100 Capsules



METHYLPHENIDATE HYDROCHLORIDE methylphenidate hydrochloride capsule, extended release

Product InformationProduct Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0115-1736

Route of Administration ORAL DEA Schedule CII

Active Ingredient/Active MoietyIngredient Name Basis of Strength Strength

METHYLPHENIDATE HYDROCHLORIDE (UNII: 4B3SC438HI)(METHYLPHENIDATE - UNII:207ZZ9QZ49)

METHYLPHENIDATEHYDROCHLORIDE 10 mg

Inactive IngredientsIngredient Name Strength

POVIDONE (UNII: FZ989GH94E) HYPROMELLOSES (UNII: 3NXW29V3WO) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) ETHYLCELLULOSES (UNII: 7Z8S9VYZ4B) CETYL ALCOHOL (UNII: 936JST6JCN) SODIUM LAURYL SULFATE (UNII: 368GB5141J) DIBUTYL SEBACATE (UNII: 4W5IH7FLNY) GELATIN (UNII: 2G86QN327L) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) FD&C BLUE NO. 2 (UNII: L06K8R7DQK) FERRIC OXIDE YELLOW (UNII: EX438O2MRT)

Product CharacteristicsColor white (white body) , green (green cap) Score no scoreShape CAPSULE Size 14mmFlavor Imprint Code CP;401;10mgContains

Packaging# Item Code Package Description Marketing Start

DateMarketing End

Date1 NDC:0115-1736-

01100 in 1 BOTTLE; Type 0: Not a CombinationProduct 09/20/2016

Marketing InformationMarketingCategory

Application Number or MonographCitation

Marketing StartDate

Marketing EndDate

ANDA ANDA205105 09/20/2016








POVIDONE (UNII: FZ989GH94E) HYPROMELLOSES (UNII: 3NXW29V3WO) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) ETHYLCELLULOSES (UNII: 7Z8S9VYZ4B) CETYL ALCOHOL (UNII: 936JST6JCN) SODIUM LAURYL SULFATE (UNII: 368GB5141J) DIBUTYL SEBACATE (UNII: 4W5IH7FLNY) GELATIN (UNII: 2G86QN327L) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) D&C RED NO. 28 (UNII: 767IP0Y5NH) FD&C BLUE NO. 1 (UNII: H3R47K3TBD) FD&C GREEN NO. 3 (UNII: 3P3ONR6O1S)

Product CharacteristicsColor white (white body) , blue (blue cap) Score no score

Shape CAPSULE Size 16mmFlavor Imprint Code CP;402;20mgContains


DateMarketing End

Date1 NDC:0115-1737-




Marketing StartDate

Marketing EndDate

ANDA ANDA205105 09/20/2016








POVIDONE (UNII: FZ989GH94E) HYPROMELLOSES (UNII: 3NXW29V3WO) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) ETHYLCELLULOSES (UNII: 7Z8S9VYZ4B) CETYL ALCOHOL (UNII: 936JST6JCN) SODIUM LAURYL SULFATE (UNII: 368GB5141J) DIBUTYL SEBACATE (UNII: 4W5IH7FLNY) GELATIN (UNII: 2G86QN327L) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) FERROSOFERRIC OXIDE (UNII: XM0M87F357) FERRIC OXIDE RED (UNII: 1K09F3G675) FERRIC OXIDE YELLOW (UNII: EX438O2MRT)

Product CharacteristicsColor white (white body) , brown (brown cap) Score no scoreShape CAPSULE Size 18mmFlavor Imprint Code CP;403;30mgContains


DateMarketing End

Date1 NDC:0115-1738-




Marketing StartDate

Marketing EndDate

ANDA ANDA205105 09/20/2016








POVIDONE (UNII: FZ989GH94E) HYPROMELLOSES (UNII: 3NXW29V3WO) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) ETHYLCELLULOSES (UNII: 7Z8S9VYZ4B) CETYL ALCOHOL (UNII: 936JST6JCN) SODIUM LAURYL SULFATE (UNII: 368GB5141J) DIBUTYL SEBACATE (UNII: 4W5IH7FLNY) GELATIN (UNII: 2G86QN327L) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C RED NO. 40 (UNII: WZB9127XOA)

Product CharacteristicsColor white (white body) , yellow (yellow cap) Score no scoreShape CAPSULE Size 19mmFlavor Imprint Code CP;404;40mgContains


DateMarketing End

Date1 NDC:0115-1739-




Marketing StartDate

Marketing EndDate

ANDA ANDA205105 09/20/2016








POVIDONE (UNII: FZ989GH94E) HYPROMELLOSES (UNII: 3NXW29V3WO) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) ETHYLCELLULOSES (UNII: 7Z8S9VYZ4B) CETYL ALCOHOL (UNII: 936JST6JCN) SODIUM LAURYL SULFATE (UNII: 368GB5141J) DIBUTYL SEBACATE (UNII: 4W5IH7FLNY) GELATIN (UNII: 2G86QN327L) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) D&C RED NO. 28 (UNII: 767IP0Y5NH)

FD&C GREEN NO. 3 (UNII: 3P3ONR6O1S) FERROSOFERRIC OXIDE (UNII: XM0M87F357)

Product CharacteristicsColor white (white body) , blue (navy cap) Score no scoreShape CAPSULE Size 22mmFlavor Imprint Code CP;405;50mgContains


DateMarketing End

Date1 NDC:0115-1740-




Marketing StartDate

Marketing EndDate

ANDA ANDA205105 09/20/2016








POVIDONE (UNII: FZ989GH94E) HYPROMELLOSES (UNII: 3NXW29V3WO) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) ETHYLCELLULOSES (UNII: 7Z8S9VYZ4B) CETYL ALCOHOL (UNII: 936JST6JCN) SODIUM LAURYL SULFATE (UNII: 368GB5141J) DIBUTYL SEBACATE (UNII: 4W5IH7FLNY) GELATIN (UNII: 2G86QN327L)

Amneal Pharmaceuticals of New York LLC

TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Product CharacteristicsColor white (white opaque) Score no scoreShape CAPSULE Size 22mmFlavor Imprint Code CP;406;60mgContains


DateMarketing End

Date1 NDC:0115-1741-




Marketing StartDate

Marketing EndDate

ANDA ANDA205105 09/20/2016

Labeler - Amneal Pharmaceuticals of New York LLC (123797875)

EstablishmentName Address ID/FEI Business Operations

AmnealPharmaceuticalsof New York,LLC

123797875

analys is(0115-1736, 0115-1737, 0115-1738, 0115-1739, 0115-1740, 0115-1741) , label(0115-1736, 0115-1737, 0115-1738, 0115-1739, 0115-1740, 0115-1741) , manufacture(0115-1736, 0115-1737, 0115-1738, 0115-1739, 0115-1740, 0115-1741) , pack(0115-1736, 0115-1737, 0115-1738, 0115-1739, 0115-1740, 0115-1741)

Revised: 12/2021

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