These Highlights Do Not Include All The Information Needed To Use Methylphenidate Hydrochloride Extended-release Capsules (la) Safely And Effectively. See Full Prescribing Information For Methylphenidate Hydrochloride Extended-release Capsules (la).

Exacerbation of Preexisting Psychosis

CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F and 86°F). [See USP controlled room temperature].

Dispense in tight container (USP).

CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA), have a high potential for abuse. Abuse is characterized by impaired control over drug use despite harm, and craving.

Signs and symptoms of CNS stimulant abuse include increased heart rate, respiratory rate, blood pressure, and/or 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. Abusers of CNS stimulants may chew, snort, inject, or use other unapproved routes of administration which may result in overdose and death [see Overdosage (10)] .

To reduce the abuse of CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA), assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and on proper storage and disposal of CNS stimulants [see How Supplied/Storage and Handling (16)] , monitor for signs of abuse while on therapy, and reevaluate the need for methylphenidate hydrochloride tablets and methylphenidate hydrochloride extended-release tablets use.

Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.

Methylphenidate hydrochloride extended-release capsules (LA) contains methylphenidate hydrochloride USP, a CNS stimulant.

Methylphenidate hydrochloride extended-release capsules (LA) is an extended-release formulation of methylphenidate for oral administration with a bi-modal release profile. Each bead-filled methylphenidate hydrochloride extended-release capsule (LA) contains half the dose as immediate-release beads and half as enteric-coated beads, thus providing an immediate release of methylphenidate and a second delayed release of methylphenidate.

The active substance in methylphenidate hydrochloride extended-release capsules (LA) is methyl α-phenyl-2-piperidineacetate hydrochloride, and its structural formula is

Methylphenidate hydrochloride USP is a white, odorless, fine 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 g/mol.

Inactive ingredients: Sugar spheres (which contain sucrose and starch (corn)), hypromellose, cellulose acetate butyrate, hypromellose acetate succinate, acetyltributyl citrate, acetone, talc, and purified water. Opaque gelatin capsules contain: titanium dioxide and gelatin. The 10mg capsule contains FD&C Green#3, FD&C#40, and FD&C Yellow #6. The 30 and 40 mg capsules contain D&C Red #28 and FD&C Blue #1. The 60 mg capsules contain iron oxide yellow and sodium lauryl sulfate. The capsules are imprinted with black ink which contains black iron oxide, shellac and potassium hydroxide. The 60 mg black imprinting ink also contains ammonium hydroxide and propylene glycol.

The safety and effectiveness of methylphenidate hydrochloride extended-release capsules (LA) for the treatment of ADHD have been established in pediatric patients 6 to 12 years.

The safety and effectiveness of methylphenidate hydrochloride extended-release capsules (LA) in pediatric patients less than 6 years have not been established. The long-term efficacy of methylphenidate hydrochloride extended-release capsules (LA) in pediatric patients has not been established.

Methylphenidate hydrochloride extended-release capsules (LA) has not been studied in the geriatric population.

• Hypersensitivity to methylphenidate or other components of methylphenidate hydrochloride extended-release capsules (LA). Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been reported in patients treated with methylphenidate [see Adverse Reactions (6.1)].
• Concomitant treatment with monoamine oxidase inhibitors (MAOIs), or within 14 days following discontinuation of treatment with an MAOI, because of the risk of hypertensive crises [s ee Drug Interactions (7.1)].

The following are discussed in more detail in other sections of the labeling:

• Abuse and Dependence [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)]
• Known hypersensitivity to methylphenidate or other ingredients of methylphenidate hydrochloride extended-release capsules (LA) [see Contraindications (4)]
• Hypertensive crisis when used concomitantly with Monoamine Oxidase Inhibitors [see Contraindications (4), Drug Interactions (7.1)]
• Serious Cardiovascular Reactions [see Warnings and Precautions (5.2)]
• Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3)]
• Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
• Priapism [see Warnings and Precautions (5.5)]
• Peripheral Vasculopathy, Including Raynaud's Phenomenon [see Warnings and Precautions (5.6)]
• Long-Term Suppression of Growth [see Warnings and Precautions (5.7)]

• Antihypertensive drugs: Monitor blood pressure and heart. Adjust dosage of antihypertensive drug as needed ( 7.1).
• Halogenated Anesthetics:Avoid use of methylphenidate hydrochloride extended-release capsules (LA) on the day of surgery if halogenated anesthetics will be used ( 7.1).

Methylphenidate is a racemic mixture comprised of the d-and l-threoenantiomers. The d-threoenantiomer is more pharmacologically active than the l-threoenantiomer. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

Methylphenidate hydrochloride extended-release capsules (LA) produces a bi-modal plasma concentration-time profile (i.e., 2 distinct peaks approximately 4 hours apart) when administered orally to children diagnosed with ADHD and healthy adults.

No accumulation of methylphenidate is expected following multiple once daily oral dosing with methylphenidate hydrochloride extended-release capsules (LA), however, there is a slight upward trend in the methylphenidate area under the curve and peak plasma concentrations (C _max1and C _max2) after oral administration of methylphenidate hydrochloride extended-release capsules (LA) 20 mg and 40 mg to adults.

Methylphenidate hydrochloride extended-release capsules (LA) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), in pediatric patients 6 to 12 years of age [see Clinical Studies (14)] .

Methylphenidate hydrochloride is a CNS stimulant. The mode of therapeutic action in ADHD is not known.

Methylphenidate hydrochloride extended-release capsules (LA) contains methylphenidate hydrochloride, a Schedule II controlled substance.

Prior to initiating treatment with central nervous system (CNS) stimulants, including methylphenidate hydrochloride extended-release capsules (LA), assess for the presence of cardiac disease (i.e., perform a careful history, including family history of sudden death or ventricular arrhythmia, and physical examination) [see Warnings and Precautions (5.2)] .

Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Maintain careful prescription records, educate patients about abuse, monitor for signs of abuse and overdose, and periodically reevaluate the need for methylphenidate hydrochloride extended-release capsules (LA) use [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)].

• Serious Cardiovascular Events: Sudden death has been reported in association with CNS-stimulant treatment at usual doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infarction have been reported. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm arrhythmias, or coronary artery disease ( 5.2).
• Blood Pressure and Heart Rate Increases: Monitor blood pressure and pulse. Consider the benefits and risk in patients for whom an increase in blood pressure or heart rate would be problematic ( 5.3).
• Psychiatric Adverse Reactions: Use of stimulants may cause psychotic or manic symptoms in patients with no prior history or exacerbation of symptoms in patients with preexisting psychiatric illness. Evaluate for preexisting psychotic or bipolar disorder prior to methylphenidate hydrochloride extended-release capsules (LA) use ( 5.4).
• Priapism: Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed ( 5.5).
• Peripheral Vasculopathy, including Raynaud's Phenomenon: Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants ( 5.6).
• Long-Term Suppression of Growth: Monitor height and weight at appropriate intervals in pediatric patients ( 5.7).

• Administer orally once daily in the morning ( 2.2).
• Capsules may be swallowed whole, or opened and the entire contents sprinkled on applesauce ( 2.2).
• Should not be crushed, chewed, or divided ( 2.2).
• Patients new to methylphenidate: Start at 20 mg daily, titrating the dose weekly in 10-mg increments. Doses above 60 mg daily are not recommended ( 2.3).
• For patients currently using methylphenidate hydrochloride tablets or methylphenidate hydrochloride extended-release tablets: Dosage is based on current dose regimen ( 2.4).
• If switching from other methylphenidate products, discontinue treatment and titrate with methylphenidate hydrochloride extended-release capsules (LA) ( 2.4).

• 10 mg extended-release capsules white/light green (imprinted mayne 609 on both the body and cap)
• 20 mg extended-release capsules white/white (imprinted mayne 610 on both the body and cap)
• 30 mg extended-release capsules white/light blue, (imprinted mayne 611 on both body and cap)
• 40 mg extended-release capsules white/dark blue, (imprinted mayne 612 on both body and cap)
• 60 mg extended-release capsules light yellow/dark yellow (imprinted mayne 614 on both body and cap)

The following adverse reactions have been identified during the post approval use of methylphenidate products. 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.

Methylphenidate hydrochloride extended-release capsules (LA) was evaluated in a randomized, double-blind, placebo-controlled, parallel group clinical study in which 134 children, ages 6 to 12, with DSM-IV diagnoses of ADHD received a single morning dose of methylphenidate hydrochloride extended-release capsules (LA)in the range of 10 to 40 mg/day, or placebo, for up to 2 weeks. The doses used were the optimal doses established in a previous individual dose titration phase. In that titration phase, 53 of 164 patients (32%) started on a daily dose of 10 mg and 111 of 164 patients (68%) started on a daily dose of 20 mg or higher. The patient's regular schoolteacher completed the Conners ADHD/DSM-IV Scale for Teachers (CADS-T) at baseline and the end of each week. The CADS-T assesses symptoms of hyperactivity and inattention. The change from baseline of the (CADS-T) scores during the last week of treatment was analyzed as the primary efficacy parameter. Patients treated with methylphenidate hydrochloride extended-release capsules (LA) showed a statistically significant improvement in symptom scores from baseline [Mean (final score - baseline) = -10.7 points)] over patients who received placebo [Mean (final score - baseline) = +2.8 points ]. The lower the final score on the CADS-T scale from baseline, the less severe the disease is. This demonstrates that a single morning dose of methylphenidate hydrochloride extended-release capsules (LA) exerts a treatment effect in ADHD.

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 practice.

The clinical program for methylphenidate hydrochloride extended-release capsules (LA) consisted of 6 studies: 2 controlled clinical studies conducted in children with ADHD aged 6 to 12 years and 4 clinical pharmacology studies conducted in healthy adult volunteers. These studies included a total of 256 subjects; 195 children with ADHD and 61 healthy adult volunteers. The subjects received methylphenidate hydrochloride extended-release capsules (LA) in doses of 10 to 40 mg per day. Safety of methylphenidate hydrochloride extended-release capsules (LA) was assessed by evaluating frequency and nature of adverse events, routine laboratory tests, vital signs, and body weight. A placebo-controlled, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of methylphenidate hydrochloride extended-release capsules (LA) in children with ADHD aged 6 to 12 years. All subjects received methylphenidate hydrochloride extended-release capsules (LA) for up to 4 weeks, and had their dose optimally adjusted, prior to entering the double-blind phase of the trial. In the 2-week double-blind treatment phase of this study, patients received either placebo or methylphenidate hydrochloride extended-release capsules (LA) at their individually-titrated dose (range, 10 to 40 mg).

Adverse reactions with an incidence greater than 5% during the initial 4-week single-blind methylphenidate hydrochloride extended-release capsules (LA) titration period of this study were headache, insomnia, upper abdominal pain, appetite decreased, and anorexia.

Adverse reactions with an incidence greater than 2% among methylphenidate hydrochloride extended-release capsules (LA) -treated subjects, during the 2-week double-blind phase of the clinical study, are shown in Table 2:

CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA), other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Warning and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)] .

The recommended starting dose for methylphenidate hydrochloride extended-release capsules (LA) is 20 mg once daily. Increase dosage gradually, in increments of 10 mg weekly. Daily dosage above 60 mg is not recommended. When a lower initial dose is appropriate, patients may begin treatment with 10 mg.

Administer methylphenidate hydrochloride extended-release capsules (LA) orally once daily in the morning. Methylphenidate hydrochloride extended-release capsules (LA) may be swallowed as whole capsules or may be administered by sprinkling the capsule contents on a small amount of applesauce (see specific instructions below). Methylphenidate hydrochloride extended-release capsules (LA) and/or their contents should not be crushed, chewed, or divided.

The capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The applesauce should not be warm because it could affect the modified release properties of this formulation. The mixture of drug and applesauce should be consumed immediately in its entirety. The drug and applesauce mixture should not be stored for future use.

Pharmacological treatment of ADHD may be needed for extended periods. Periodically reevaluate the long-term use of methylphenidate hydrochloride tablets and methylphenidate hydrochloride extended-release tablets, and adjust dosage as needed.

Advise the patient to read the FDA-approved patient labeling (Medication Guide)

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.

Careful follow-up of weight and height in pediatric 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 10-13 years), suggests that consistently medicated pediatric patients (i.e., treatment for 7 days per week throughout the year) have 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 period of development.

Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA). Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

10 mg white/light green capsules (imprinted mayne 609 on both the body and the cap)

20 mg white/white capsules (imprinted mayne 610 on both the body and cap

30 mg white/light blue capsules (imprinted mayne 611 on both the body and cap

40 mg white/dark blue capsules (imprinted mayne 612 on both the body and cap)

60 mg light yellow/dark yellow capsules (imprinted mayne 614 on both the body and cap)

Sudden death, stroke, and myocardial infarction have been reported in adults with CNS-stimulant treatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during methylphenidate hydrochloride extended-release capsules (LA) treatment.

If paradoxical worsening of symptoms or other adverse reactions occur, reduce the dosage, or, if necessary, discontinue methylphenidate hydrochloride extended-release capsules (LA). If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.

CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA), other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Boxed Warning, Drug Abuse and Dependence (9.2, 9.3)].

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). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia.

If switching from other methylphenidate products, discontinue that treatment, and titrate with methylphenidate hydrochloride extended-release capsules (LA) using the titration schedule.

Do not substitute for other methylphenidate products on a milligram-per-milligram basis, because different methylphenidate base compositions and differing pharmacokinetic profiles [see Description (11), Clinical Pharmacology (12.3)] .

Clinical judgment should be used when selecting the starting dose. Daily dosage above 60 mg is not recommended.

NDC 51862-609-01

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

10 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

100 Capsules

maynepharma

NDC 51862-610-01

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

20 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

100 Capsules

maynepharma

NDC 51862-611-01

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

30 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

100 Capsules

maynepharma

NDC 51862-612-01

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

40 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

100 Capsules

maynepharma

NDC 51862-614-30

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

60 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

30 Capsules

maynepharma

CNS Stimulants, including methylphenidate hydrochloride extended-release capsules (LA), used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Table 3 presents clinically important drug interactions with methylphenidate hydrochloride extended-release capsules (LA)

The recommended dose of methylphenidate hydrochloride extended-release capsules (LA) for patients currently taking methylphenidate hydrochloride tablets twice daily or methylphenidate hydrochloride extended-release tablets (SR) is provided below.

Exacerbation of Preexisting Psychosis

CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F and 86°F). [See USP controlled room temperature].

Dispense in tight container (USP).

CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA), have a high potential for abuse. Abuse is characterized by impaired control over drug use despite harm, and craving.

Signs and symptoms of CNS stimulant abuse include increased heart rate, respiratory rate, blood pressure, and/or 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. Abusers of CNS stimulants may chew, snort, inject, or use other unapproved routes of administration which may result in overdose and death [see Overdosage (10)] .

To reduce the abuse of CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA), assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and on proper storage and disposal of CNS stimulants [see How Supplied/Storage and Handling (16)] , monitor for signs of abuse while on therapy, and reevaluate the need for methylphenidate hydrochloride tablets and methylphenidate hydrochloride extended-release tablets use.

Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.

Methylphenidate hydrochloride extended-release capsules (LA) contains methylphenidate hydrochloride USP, a CNS stimulant.

Methylphenidate hydrochloride extended-release capsules (LA) is an extended-release formulation of methylphenidate for oral administration with a bi-modal release profile. Each bead-filled methylphenidate hydrochloride extended-release capsule (LA) contains half the dose as immediate-release beads and half as enteric-coated beads, thus providing an immediate release of methylphenidate and a second delayed release of methylphenidate.

The active substance in methylphenidate hydrochloride extended-release capsules (LA) is methyl α-phenyl-2-piperidineacetate hydrochloride, and its structural formula is

Methylphenidate hydrochloride USP is a white, odorless, fine 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 g/mol.

Inactive ingredients: Sugar spheres (which contain sucrose and starch (corn)), hypromellose, cellulose acetate butyrate, hypromellose acetate succinate, acetyltributyl citrate, acetone, talc, and purified water. Opaque gelatin capsules contain: titanium dioxide and gelatin. The 10mg capsule contains FD&C Green#3, FD&C#40, and FD&C Yellow #6. The 30 and 40 mg capsules contain D&C Red #28 and FD&C Blue #1. The 60 mg capsules contain iron oxide yellow and sodium lauryl sulfate. The capsules are imprinted with black ink which contains black iron oxide, shellac and potassium hydroxide. The 60 mg black imprinting ink also contains ammonium hydroxide and propylene glycol.

The safety and effectiveness of methylphenidate hydrochloride extended-release capsules (LA) for the treatment of ADHD have been established in pediatric patients 6 to 12 years.

The safety and effectiveness of methylphenidate hydrochloride extended-release capsules (LA) in pediatric patients less than 6 years have not been established. The long-term efficacy of methylphenidate hydrochloride extended-release capsules (LA) in pediatric patients has not been established.

Methylphenidate hydrochloride extended-release capsules (LA) has not been studied in the geriatric population.

• Hypersensitivity to methylphenidate or other components of methylphenidate hydrochloride extended-release capsules (LA). Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been reported in patients treated with methylphenidate [see Adverse Reactions (6.1)].
• Concomitant treatment with monoamine oxidase inhibitors (MAOIs), or within 14 days following discontinuation of treatment with an MAOI, because of the risk of hypertensive crises [s ee Drug Interactions (7.1)].

The following are discussed in more detail in other sections of the labeling:

• Abuse and Dependence [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)]
• Known hypersensitivity to methylphenidate or other ingredients of methylphenidate hydrochloride extended-release capsules (LA) [see Contraindications (4)]
• Hypertensive crisis when used concomitantly with Monoamine Oxidase Inhibitors [see Contraindications (4), Drug Interactions (7.1)]
• Serious Cardiovascular Reactions [see Warnings and Precautions (5.2)]
• Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3)]
• Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
• Priapism [see Warnings and Precautions (5.5)]
• Peripheral Vasculopathy, Including Raynaud's Phenomenon [see Warnings and Precautions (5.6)]
• Long-Term Suppression of Growth [see Warnings and Precautions (5.7)]

• Antihypertensive drugs: Monitor blood pressure and heart. Adjust dosage of antihypertensive drug as needed ( 7.1).
• Halogenated Anesthetics:Avoid use of methylphenidate hydrochloride extended-release capsules (LA) on the day of surgery if halogenated anesthetics will be used ( 7.1).

Methylphenidate is a racemic mixture comprised of the d-and l-threoenantiomers. The d-threoenantiomer is more pharmacologically active than the l-threoenantiomer. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

Methylphenidate hydrochloride extended-release capsules (LA) produces a bi-modal plasma concentration-time profile (i.e., 2 distinct peaks approximately 4 hours apart) when administered orally to children diagnosed with ADHD and healthy adults.

No accumulation of methylphenidate is expected following multiple once daily oral dosing with methylphenidate hydrochloride extended-release capsules (LA), however, there is a slight upward trend in the methylphenidate area under the curve and peak plasma concentrations (C _max1and C _max2) after oral administration of methylphenidate hydrochloride extended-release capsules (LA) 20 mg and 40 mg to adults.

Methylphenidate hydrochloride extended-release capsules (LA) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), in pediatric patients 6 to 12 years of age [see Clinical Studies (14)] .

Methylphenidate hydrochloride is a CNS stimulant. The mode of therapeutic action in ADHD is not known.

Methylphenidate hydrochloride extended-release capsules (LA) contains methylphenidate hydrochloride, a Schedule II controlled substance.

Prior to initiating treatment with central nervous system (CNS) stimulants, including methylphenidate hydrochloride extended-release capsules (LA), assess for the presence of cardiac disease (i.e., perform a careful history, including family history of sudden death or ventricular arrhythmia, and physical examination) [see Warnings and Precautions (5.2)] .

Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Maintain careful prescription records, educate patients about abuse, monitor for signs of abuse and overdose, and periodically reevaluate the need for methylphenidate hydrochloride extended-release capsules (LA) use [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)].

• Serious Cardiovascular Events: Sudden death has been reported in association with CNS-stimulant treatment at usual doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infarction have been reported. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm arrhythmias, or coronary artery disease ( 5.2).
• Blood Pressure and Heart Rate Increases: Monitor blood pressure and pulse. Consider the benefits and risk in patients for whom an increase in blood pressure or heart rate would be problematic ( 5.3).
• Psychiatric Adverse Reactions: Use of stimulants may cause psychotic or manic symptoms in patients with no prior history or exacerbation of symptoms in patients with preexisting psychiatric illness. Evaluate for preexisting psychotic or bipolar disorder prior to methylphenidate hydrochloride extended-release capsules (LA) use ( 5.4).
• Priapism: Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed ( 5.5).
• Peripheral Vasculopathy, including Raynaud's Phenomenon: Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants ( 5.6).
• Long-Term Suppression of Growth: Monitor height and weight at appropriate intervals in pediatric patients ( 5.7).

• Administer orally once daily in the morning ( 2.2).
• Capsules may be swallowed whole, or opened and the entire contents sprinkled on applesauce ( 2.2).
• Should not be crushed, chewed, or divided ( 2.2).
• Patients new to methylphenidate: Start at 20 mg daily, titrating the dose weekly in 10-mg increments. Doses above 60 mg daily are not recommended ( 2.3).
• For patients currently using methylphenidate hydrochloride tablets or methylphenidate hydrochloride extended-release tablets: Dosage is based on current dose regimen ( 2.4).
• If switching from other methylphenidate products, discontinue treatment and titrate with methylphenidate hydrochloride extended-release capsules (LA) ( 2.4).

• 10 mg extended-release capsules white/light green (imprinted mayne 609 on both the body and cap)
• 20 mg extended-release capsules white/white (imprinted mayne 610 on both the body and cap)
• 30 mg extended-release capsules white/light blue, (imprinted mayne 611 on both body and cap)
• 40 mg extended-release capsules white/dark blue, (imprinted mayne 612 on both body and cap)
• 60 mg extended-release capsules light yellow/dark yellow (imprinted mayne 614 on both body and cap)

The following adverse reactions have been identified during the post approval use of methylphenidate products. 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.

Methylphenidate hydrochloride extended-release capsules (LA) was evaluated in a randomized, double-blind, placebo-controlled, parallel group clinical study in which 134 children, ages 6 to 12, with DSM-IV diagnoses of ADHD received a single morning dose of methylphenidate hydrochloride extended-release capsules (LA)in the range of 10 to 40 mg/day, or placebo, for up to 2 weeks. The doses used were the optimal doses established in a previous individual dose titration phase. In that titration phase, 53 of 164 patients (32%) started on a daily dose of 10 mg and 111 of 164 patients (68%) started on a daily dose of 20 mg or higher. The patient's regular schoolteacher completed the Conners ADHD/DSM-IV Scale for Teachers (CADS-T) at baseline and the end of each week. The CADS-T assesses symptoms of hyperactivity and inattention. The change from baseline of the (CADS-T) scores during the last week of treatment was analyzed as the primary efficacy parameter. Patients treated with methylphenidate hydrochloride extended-release capsules (LA) showed a statistically significant improvement in symptom scores from baseline [Mean (final score - baseline) = -10.7 points)] over patients who received placebo [Mean (final score - baseline) = +2.8 points ]. The lower the final score on the CADS-T scale from baseline, the less severe the disease is. This demonstrates that a single morning dose of methylphenidate hydrochloride extended-release capsules (LA) exerts a treatment effect in ADHD.

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 practice.

The clinical program for methylphenidate hydrochloride extended-release capsules (LA) consisted of 6 studies: 2 controlled clinical studies conducted in children with ADHD aged 6 to 12 years and 4 clinical pharmacology studies conducted in healthy adult volunteers. These studies included a total of 256 subjects; 195 children with ADHD and 61 healthy adult volunteers. The subjects received methylphenidate hydrochloride extended-release capsules (LA) in doses of 10 to 40 mg per day. Safety of methylphenidate hydrochloride extended-release capsules (LA) was assessed by evaluating frequency and nature of adverse events, routine laboratory tests, vital signs, and body weight. A placebo-controlled, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of methylphenidate hydrochloride extended-release capsules (LA) in children with ADHD aged 6 to 12 years. All subjects received methylphenidate hydrochloride extended-release capsules (LA) for up to 4 weeks, and had their dose optimally adjusted, prior to entering the double-blind phase of the trial. In the 2-week double-blind treatment phase of this study, patients received either placebo or methylphenidate hydrochloride extended-release capsules (LA) at their individually-titrated dose (range, 10 to 40 mg).

Adverse reactions with an incidence greater than 5% during the initial 4-week single-blind methylphenidate hydrochloride extended-release capsules (LA) titration period of this study were headache, insomnia, upper abdominal pain, appetite decreased, and anorexia.

Adverse reactions with an incidence greater than 2% among methylphenidate hydrochloride extended-release capsules (LA) -treated subjects, during the 2-week double-blind phase of the clinical study, are shown in Table 2:

CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA), other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Warning and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)] .

The recommended starting dose for methylphenidate hydrochloride extended-release capsules (LA) is 20 mg once daily. Increase dosage gradually, in increments of 10 mg weekly. Daily dosage above 60 mg is not recommended. When a lower initial dose is appropriate, patients may begin treatment with 10 mg.

Administer methylphenidate hydrochloride extended-release capsules (LA) orally once daily in the morning. Methylphenidate hydrochloride extended-release capsules (LA) may be swallowed as whole capsules or may be administered by sprinkling the capsule contents on a small amount of applesauce (see specific instructions below). Methylphenidate hydrochloride extended-release capsules (LA) and/or their contents should not be crushed, chewed, or divided.

The capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The applesauce should not be warm because it could affect the modified release properties of this formulation. The mixture of drug and applesauce should be consumed immediately in its entirety. The drug and applesauce mixture should not be stored for future use.

Pharmacological treatment of ADHD may be needed for extended periods. Periodically reevaluate the long-term use of methylphenidate hydrochloride tablets and methylphenidate hydrochloride extended-release tablets, and adjust dosage as needed.

Advise the patient to read the FDA-approved patient labeling (Medication Guide)

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.

Careful follow-up of weight and height in pediatric 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 10-13 years), suggests that consistently medicated pediatric patients (i.e., treatment for 7 days per week throughout the year) have 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 period of development.

Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA). Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

10 mg white/light green capsules (imprinted mayne 609 on both the body and the cap)

20 mg white/white capsules (imprinted mayne 610 on both the body and cap

30 mg white/light blue capsules (imprinted mayne 611 on both the body and cap

40 mg white/dark blue capsules (imprinted mayne 612 on both the body and cap)

60 mg light yellow/dark yellow capsules (imprinted mayne 614 on both the body and cap)

Sudden death, stroke, and myocardial infarction have been reported in adults with CNS-stimulant treatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during methylphenidate hydrochloride extended-release capsules (LA) treatment.

If paradoxical worsening of symptoms or other adverse reactions occur, reduce the dosage, or, if necessary, discontinue methylphenidate hydrochloride extended-release capsules (LA). If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.

CNS stimulants, including methylphenidate hydrochloride extended-release capsules (LA), other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Boxed Warning, Drug Abuse and Dependence (9.2, 9.3)].

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). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia.

If switching from other methylphenidate products, discontinue that treatment, and titrate with methylphenidate hydrochloride extended-release capsules (LA) using the titration schedule.

Do not substitute for other methylphenidate products on a milligram-per-milligram basis, because different methylphenidate base compositions and differing pharmacokinetic profiles [see Description (11), Clinical Pharmacology (12.3)] .

Clinical judgment should be used when selecting the starting dose. Daily dosage above 60 mg is not recommended.

NDC 51862-609-01

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

10 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

100 Capsules

maynepharma

NDC 51862-610-01

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

20 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

100 Capsules

maynepharma

NDC 51862-611-01

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

30 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

100 Capsules

maynepharma

NDC 51862-612-01

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

40 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

100 Capsules

maynepharma

NDC 51862-614-30

Once Daily

Methylphenidate

Hydrochloride

CII

Extended-Release Capsules (LA)

60 mg

PHARMACIST: Please dispense with

Medication Guide provided separately.

Rx Only

30 Capsules

maynepharma

CNS Stimulants, including methylphenidate hydrochloride extended-release capsules (LA), used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Table 3 presents clinically important drug interactions with methylphenidate hydrochloride extended-release capsules (LA)

The recommended dose of methylphenidate hydrochloride extended-release capsules (LA) for patients currently taking methylphenidate hydrochloride tablets twice daily or methylphenidate hydrochloride extended-release tablets (SR) is provided below.