METHYLPHENIDATE HYDROCHLORIDE tablet, extended release

United States - English - NLM (National Library of Medicine)

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Active ingredient:
METHYLPHENIDATE HYDROCHLORIDE (UNII: 4B3SC438HI) (METHYLPHENIDATE - UNII:207ZZ9QZ49)
Available from:
Trigen Laboratories, LLC
INN (International Name):
METHYLPHENIDATE HYDROCHLORIDE
Composition:
METHYLPHENIDATE HYDROCHLORIDE 54 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Methylphenidate hydrochloride extended-release tablets USP is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children 6 years of age and older, adolescents, and adults up to the age of 65 [see Clinical Studies (14)] . A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; lo
Product summary:
Methylphenidate hydrochloride extended-release tablets are available in 18, 27, 36, 54, and 72 mg strengths.  The 18 mg tablets are yellow with “TL706” imprinted in black ink, 27 mg tablets are gray with “TL707” imprinted in black ink, 36 mg tablets are white with “TL708” imprinted in black ink, 54 mg tablets are pink with “TL709" imprinted in black ink, and 72 mg tablets are blue with “TL710” imprinted in black ink. The tablets are supplied: Storage and Handling Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from humidity.
Authorization status:
Abbreviated New Drug Application
Authorization number:
13811-706-10, 13811-707-10, 13811-708-10, 13811-709-10, 13811-710-10, 13811-710-30

Trigen Laboratories, LLC

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MedGuide

MEDICATION GUIDE

Methylphenidate hydrochloride extended-release tablets USP CII

(METH-il-FEN-i-date)

Read the Medication Guide that comes with methylphenidate hydrochloride extended-release tablets USP

before you or your child starts taking it and each time you get a refill. There may be new information. This

Medication Guide does not take the place of talking to your doctor about your or your child's treatment with

methylphenidate hydrochloride extended-release tablets USP.

What is the most important information I should know about methylphenidate hydrochloride extended-

release tablets?

The following have been reported with use of methylphenidate HCl and other stimulant medicines:

1. Heart-related problems:

· sudden death in patients who have heart problems or heart defects

· stroke and heart attack in adults

· increased blood pressure and heart rate

Tell your doctor if you or your child has any heart problems, heart defects, high blood pressure, or a family

history of these problems.

Your doctor should check you or your child carefully for heart problems before starting methylphenidate

hydrochloride extended-release tablets.

Your doctor should check you or your child's blood pressure and heart rate regularly during treatment with

methylphenidate hydrochloride extended-release tablets.

Call your doctor right away if you or your child has any signs of heart problems such as chest pain, shortness

of breath, or fainting while taking methylphenidate hydrochloride extended-release tablets.

2. Mental (Psychiatric) problems:

All Patients

· new or worse behavior and thought problems

· new or worse bipolar illness

· new or worse aggressive behavior or hostility

Children and Teenagers

· new psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or

new manic symptoms

Tell your doctor about any mental problems you or your child have, or about a family history of suicide,

bipolar illness, or depression.

Call your doctor right away if you or your child has any new or worsening mental symptoms or problems

while taking methylphenidate hydrochloride extended-release tablets, especially seeing or hearing things that

are not real, believing things that are not real, or are suspicious.

3. Painful and prolonged erections (priapism)

Painful and prolonged erections (priapism) have occurred with methylphenidate. If you or your child develop

priapism, seek medical help right away. Because of the potential for lasting damage, priapism should be

evaluated by a doctor immediately.

4. Circulation problems in fingers and toes

[Peripheral vasculopathy, including Raynaud’s phenomenon]:

fingers or toes may feel numb, cool, painful

fingers or toes may change color from pale, to blue, to red

Tell your doctor if you have or your child has numbness, pain, skin color change, or sensitivity to

temperature in your fingers or toes.

Call your doctor right away if you have or your child has any signs of unexplained wounds appearing on

fingers or toes while taking methylphenidate hydrochloride extended release tablets.

What is methylphenidate hydrochloride extended-release tablets?

Methylphenidate hydrochloride extended-release tablets are a central nervous system stimulant prescription

medicine. It is used for the treatment of attention deficit and hyperactivity disorder (ADHD).

Methylphenidate hydrochloride extended-release tablets may help increase attention and decrease

impulsiveness and hyperactivity in patients with ADHD.

Methylphenidate hydrochloride extended-release tablets should be used as a part of a total treatment program

for ADHD that may include counseling or other therapies.

Methylphenidate hydrochloride extended-release tablets are a federally controlled substance (CII) because it

can be abused or lead to dependence. Keep methylphenidate hydrochloride extended-release tablets in a safe

place to prevent misuse and abuse. Selling or giving away methylphenidate hydrochloride extended-release

tablets may harm others, and is against the law.

Tell your doctor if you or your child have (or have a family history of) ever abused or been dependent on

alcohol, prescription medicines, or street drugs.

Who should not take methylphenidate hydrochloride extended-release tablets?

Methylphenidate hydrochloride extended-release tablets should not be taken if you or your child:

· is very anxious, tense, or agitated

· have an eye problem called glaucoma

· have tics or Tourette's syndrome, or a family history of Tourette's syndrome. Tics are hard-to-control

repeated movements or sounds.

· is taking or have taken within the past 14 days an antidepression medicine called a monoamine oxidase

inhibitor or MAOI.

· is allergic to anything in methylphenidate hydrochloride extended-release tablets. See the end of this

Medication Guide for a complete list of ingredients.

Methylphenidate hydrochloride extended-release tablets should not be used in children less than 6 years old

because it has not been studied in this age group.

Methylphenidate hydrochloride extended-release tablets may not be right for you or your child. Before

starting methylphenidate hydrochloride extended-release tablets, tell your or your child's doctor about all

health conditions (or a family history of) including:

· heart problems, heart defects, or high blood pressure

· mental problems including psychosis, mania, bipolar illness, or depression

· tics or Tourette's syndrome

· seizures or have had an abnormal brain wave test (EEG)

· circulation problems in fingers and toes

· esophagus, stomach, or small or large intestine problems

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

Can methylphenidate hydrochloride extended-release tablets be taken with other medicines?

Tell your doctor about all of the medicines that you or your child take including prescription and

nonprescription medicines, vitamins, and herbal supplements. Methylphenidate hydrochloride extended-

release tablets and some medicines may interact with each other and cause serious side effects. Sometimes

the doses of other medicines will need to be adjusted while taking methylphenidate hydrochloride extended-

release tablets.

Your doctor will decide whether methylphenidate hydrochloride extended-release tablets can be taken with

other medicines.

Especially tell your doctor if you or your child takes:

· antidepression medicines including MAOIs

· seizure medicines

· blood thinner medicines

· blood pressure medicines

· cold or allergy medicines that contain decongestants

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

and pharmacist.

Do not start any new medicine while taking methylphenidate hydrochloride extended-release tablets without

talking to your doctor first.

How should methylphenidate hydrochloride extended-release tablets be taken?

· Take methylphenidate hydrochloride extended-release tablets exactly as prescribed. Your doctor may

adjust the dose until it is right for you or your child.

· Do not chew, crush, or divide the tablets. Swallow methylphenidate hydrochloride extended-release

tablets whole with water or other liquids. Tell your doctor if you or your child cannot swallow

methylphenidate hydrochloride extended-release tablets whole. A different medicine may need to be

prescribed.

· Methylphenidate hydrochloride extended-release tablets can be taken with or without food.

· Take methylphenidate hydrochloride extended-release tablets once each day in the morning.

Methylphenidate hydrochloride extended-release tablets are an extended-release tablet. It releases medication

into your or your child's body throughout the day.

· The methylphenidate hydrochloride extended-release tablet does not dissolve completely in the body

after all the medicine has been released. You or your child may sometimes notice the empty tablet in a bowel

movement. This is normal.

· From time to time, your doctor may stop methylphenidate hydrochloride extended-release tablets

treatment for a while to check ADHD symptoms.

· Your doctor may do regular checks of the blood, heart, and blood pressure while taking

methylphenidate hydrochloride extended-release tablets. Children should have their height and weight

checked often while taking methylphenidate hydrochloride extended-release tablets. Methylphenidate

hydrochloride extended-release tablets treatment may be stopped if a problem is found during these check-

ups.

· If you or your child takes too much methylphenidate hydrochloride extended-release tablets or

overdoses, call your doctor or poison control center right away, or get emergency treatment.

What are possible side effects of methylphenidate hydrochloride extended-release tablets?

See "What is the most important information I should know about methylphenidate hydrochloride extended-

release tablets?" for information on reported 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 seizures

· eyesight changes or blurred vision

· blockage of the esophagus, stomach, small or large intestine in patients who already have a narrowing

in any of these organs

Common side effects include:

decreased

appetite

dry mouth

trouble sleeping

dizziness

stomach ache

increased

sweating

headache

nausea

anxiety

weight loss

irritability

Stimulants may impair the ability of you or your child to operate potentially hazardous machinery or

vehicles. You or your child should exercise caution until you or your child is reasonably certain that

methylphenidate hydrochloride extended-release tablets does not adversely affect your or your child's ability

to engage in such activities.

Talk to your doctor if you or your child has side effects that are bothersome or do not go away.

This is not a complete list of possible side effects. Ask your doctor or pharmacist for more information.

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

1088.

You may also report side effects to Trigen Laboratories, LLC at 1-877-482-3788.

How should I store methylphenidate hydrochloride extended-release tablets?

Store methylphenidate hydrochloride extended-release tablets USP in a safe place at room temperature, 59 to

86°F (15 to 30°C). Protect from moisture.

· Keep methylphenidate hydrochloride extended-release tablets and all medicines out of the reach of

children.

General information about methylphenidate hydrochloride extended-release tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use

methylphenidate hydrochloride extended-release tablets for a condition for which it was not prescribed. Do

not give methylphenidate hydrochloride extended-release tablets to other people, even if they have the same

condition. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about methylphenidate hydrochloride

extended-release tablets If you would like more information, talk with your doctor. You can ask your doctor

or pharmacist for information about methylphenidate hydrochloride extended-release tablets that was written

for healthcare professionals. For more information about methylphenidate hydrochloride extended-release

tablets call 1-877-482-3788.

What are the ingredients in methylphenidate hydrochloride extended-release tablets?

Active Ingredient: methylphenidate HCl

Inactive Ingredients: black iron oxide, cellulose acetate, colloidal silicon dioxide, ferrosoferric oxide,

hypromellose, lactose monohydrate, magnesium stearate, phosphoric acid, polyethylene glycol, polyethylene

oxide, sodium chloride, succinic acid, titanium dioxide, triacetin. In addition,

27 mg tablets contain: FD&C Yellow #6 Aluminum Lake, FD&C Blue #2 Aluminum Lake, FD&C Red #40

Aluminum Lake

54 mg tablets contain: FD&C Yellow #6 Aluminum Lake, FD&C Red #40 Aluminum Lake, FD&C Blue #2

Aluminum Lake

72 mg tablets contain: FD&C Blue #1 Aluminum Lake

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

Trigen Laboratories, LLC

Bridgewater, NJ 08807

www.trigenlab.com

200206-01 Rev. 11/2019

Revised: 11/2019

Document Id: 5940a98d-403d-4dc9-839d-894094ed108b

34391-3

Set id: c45dc1de-adfa-4b3c-a7dc-cffbc8eac74f

Version: 38

Effective Time: 20191126

Trigen Laboratories, LLC

METHYLPHENIDATE HYDROCHLORIDE- methylphenidate hydrochloride tablet, extended

release

Trigen Laboratories, LLC

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use methylphenidate hydrochloride extended-

release tablets USP safely and effectively. See full prescribing information for METHYLPHENIDATE

hydrochloride extended-release tablets USP.

METHYLPHENIDATE hydrochloride extended-release tablets USP, for oral use CII

Initial U.S. Approval: 2000

WARNING: DRUG DEPENDENCE

See full prescribing information for complete boxed warning.

Methylphenidate hydrochloride extended-release tablets should be given cautiously to patients with a

history of drug dependence or alcoholism. Chronic abusive use can lead to marked tolerance and

psychological dependence, with varying degrees of abnormal behavior.

INDICATIONS AND USAGE

Methylphenidate hydrochloride extended-release tablets USP is a CNS stimulant indicated for the treatment of Attention

Deficit Hyperactivity Disorder (ADHD) in children 6 years of age and older, adolescents, and adults up to the age of 65. (1)

DOSAGE AND ADMINISTRATION

Methylphenidate hydrochloride extended-release tablets should be taken once daily in the morning and swallowed

whole with the aid of liquids. Methylphenidate hydrochloride extended-release tablets should not be chewed or

crushed. Methylphenidate hydrochloride extended-release tablets may be taken with or without food. (2.1)

For children and adolescents new to methylphenidate, the recommended starting dosage is 18 mg once daily. Dosage

may be increased by 18 mg/day at weekly intervals and should not exceed 54 mg/day in children and 72 mg/day in

adolescents. (2.2)

For adult patients new to methylphenidate, the recommended starting dose is 18 or 36 mg/day. Dosage may be

increased by 18 mg/day at weekly intervals and should not exceed 72 mg/day for adults. (2.2)

For patients currently using methylphenidate, dosing is based on current dose regimen and clinical judgment. (2.3)

DOSAGE FORMS AND STRENGTHS

Tablets: 18, 27, 36, 54, and 72 mg (3)

CONTRAINDICATIONS

Known hypersensitivity to the product (4.1)

Marked anxiety, tension, or agitation (4.2)

Glaucoma (4.3)

Tics or a family history or diagnosis of Tourette's syndrome (4.4)

Do not use methylphenidate hydrochloride extended-release tablets in patients currently using or within 2 weeks of

using an MAO inhibitor (4.5)

WARNINGS AND PRECAUTIONS

Serious Cardiovascular Events: Sudden death has been reported in association with CNS stimulant treatment at usual

doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Sudden death,

stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD.

Stimulant products generally should not be used in patients with known structural cardiac abnormalities,

cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious heart problems. (5.1)

Increase in Blood Pressure: Monitor patients for changes in heart rate and blood pressure and use with caution in

patients for whom an increase in blood pressure or heart rate would be problematic. (5.1)

Psychiatric Adverse Events: Use of stimulants may cause treatment-emergent psychotic or manic symptoms in

patients with no prior history, or exacerbation of symptoms in patients with preexisting psychiatric illness. Clinical

evaluation for Bipolar Disorder is recommended prior to stimulant use. Monitor for aggressive behavior. (5.2)

Seizures: Stimulants may lower the convulsive threshold. Discontinue in the presence of seizures. (5.3)

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 painful or prolonged penile erections

or priapism are observed. (5.4)

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. (5.5)

Visual Disturbance: difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

(5.7)

Long-Term Suppression of Growth: monitor height and weight at appropriate intervals in pediatric patients. (5.6)

Gastrointestinal obstruction with preexisting GI narrowing. (5.8)

Hematologic monitoring: Periodic CBC, differential, and platelet counts are advised during prolonged therapy. (5.9)

ADVERSE REACTIONS

The most common adverse reaction in double-blind clinical trials (>5%) in children and adolescents was abdominal pain

upper. The most common adverse reactions in double-blind clinical trials (>5%) in adult patients were decreased appetite,

headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis. (6.1 and 6.2)

The most common adverse reactions associated with discontinuation (≥1%) from either pediatric or adult clinical trials

were anxiety, irritability, insomnia, and blood pressure increased. (6.3)

To report SUSPECTED ADVERSE REACTIONS, contact Trigen Laboratories, LLC at 1-877-482-3788 or FDA at

1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Do not use methylphenidate hydrochloride extended-release tablets in patients currently using or within 2 weeks of

using an MAO inhibitor (7.1)

Methylphenidate hydrochloride extended-release tablets may increase blood pressure; use cautiously with

vasopressors (7.2)

Inhibition of metabolism of coumarin anticoagulants, anticonvulsants, and some antidepressants (7.3)

USE IN SPECIFIC POPULATIONS

Caution should be exercised if administered to nursing mothers (8.3)

Safety and efficacy has not been established in children less than six years old or elderly patients greater than 65 years

of age (8.4 and 8.5)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 11/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: DRUG DEPENDENCE

1 INDICATIONS AND USAGE

1.1 Special Diagnostic Considerations

1.2 Need for Comprehensive Treatment Program

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Information

2.2 Patients New to Methylphenidate

2.3 Patients Currently Using Methylphenidate

2.4 Dose Titration

2.5 Maintenance/Extended Treatment

2.6 Dose Reduction and Discontinuation

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

4.1 Hypersensitivity to Methylphenidate

4.2 Agitation

4.3 Glaucoma

4.4 Tics

4.5 Monoamine Oxidase Inhibitors

5 WARNINGS AND PRECAUTIONS

5.1 Serious Cardiovascular Events

5.2 Psychiatric Adverse Events

5.3 Seizures

5.4 Priapism

5.5 Peripheral Vasculopathy, including Raynaud's Phenomenon

5.6 Long-Term Suppression of Growth

5.7 Visual Disturbance

5.8 Potential for Gastrointestinal Obstruction

5.9 Hematologic Monitoring

6 ADVERSE REACTIONS

6.1 Commonly Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical

T rials

6.2 Other Adverse Reactions Observed in methylphenidate hydrochloride extended-release

tablets Clinical Trials

6.3 Discontinuation Due to Adverse Reactions

6.4 Tics

6.5 Blood Pressure and Heart Rate Increases

6.6 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 MAO Inhibitors

7.2 Vasopressor Agents

7.3 Coumarin Anticoagulants, Antidepressants, and Selective Serotonin Reuptake Inhibitors

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

9.2 Abuse

9.3 Dependence

10 OVERDOSAGE

10.1 Signs and Symptoms

10.2 Recommended Treatment

10.3 Poison Control Center

11 DESCRIPTION

11.1 System Components and Performance

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

14 CLINICAL STUDIES

14.1 Children

14.2 Adolescents

14.3 Adults

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

WARNING: DRUG DEPENDENCE

Methylphenidate hydrochloride extended-release tablets USP should be given cautiously to

patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to

marked tolerance and psychological dependence with varying degrees of abnormal

behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful

supervision is required during withdrawal from abusive use since severe depression may

occur. Withdrawal following chronic therapeutic use may unmask symptoms of the

underlying disorder that may require follow-up.

1 INDICATIONS AND USAGE

Methylphenidate hydrochloride extended-release tablets USP is indicated for the treatment of Attention

Deficit Hyperactivity Disorder (ADHD) in children 6 years of age and older, adolescents, and adults up

to the age of 65 [see Clinical Studies (14)].

A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies the presence of

hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7

years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or

occupational functioning, and be present in two or more settings, e.g., school (or work) and at home.

The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at

least six of the following symptoms must have persisted for at least 6 months: lack of attention to

details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks;

poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted;

forgetful. For the Hyperactive-Impulsive Type, at least six of the following symptoms must have

persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing;

difficulty with quiet activities; "on the go;" excessive talking; blurting answers; can't wait turn; intrusive.

The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.

1.1 Special Diagnostic Considerations

Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate

diagnosis requires the use of medical and special psychological, educational, and social resources.

Learning may or may not be impaired. The diagnosis must be based upon a complete history and

evaluation of the patient and not solely on the presence of the required number of DSM-IV

characteristics.

1.2 Need for Comprehensive Treatment Program

Methylphenidate hydrochloride extended-release tablets are indicated as an integral part of a total

treatment program for ADHD that may include other measures (psychological, educational, social).

Drug treatment may not be indicated for all patients with ADHD. Stimulants are not intended for use in

patients who exhibit symptoms secondary to environmental factors and/or other primary psychiatric

disorders, including psychosis. Appropriate educational placement is essential and psychosocial

intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe

stimulant medication will depend upon the physician's assessment of the chronicity and severity of the

patient's symptoms.

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Information

Methylphenidate hydrochloride extended-release tablets should be administered orally once daily in the

morning with or without food.

Methylphenidate hydrochloride extended-release tablets must be swallowed whole with the aid of

liquids, and must not be chewed, divided, or crushed [see Patient Counseling Information (17)].

2.2 Patients New to Methylphenidate

The recommended starting dose of methylphenidate hydrochloride extended-release tablets for patients

who are not currently taking methylphenidate or stimulants other than methylphenidate is 18 mg once

daily for children and adolescents and 18 or 36 mg once daily for adults (see Table 1).

TABLE 1. Methylphenidate hydrochloride extended-release tablets Recommended Starting

Doses and Dose Ranges

Patient Age

Recommended Starting Dose

Dose Range

Children 6–12 years of age

18 mg/day

18 mg – 54 mg/day

Adolescents 13–17 years of age 18 mg/day

18 mg – 72 mg/day

not to exceed 2 mg/kg/day

Adults 18–65 years of age

18 or 36 mg/day

18 mg – 72 mg/day

2.3 Patients Currently Using Methylphenidate

The recommended dose of methylphenidate hydrochloride extended-release tablets for patients who are

currently taking methylphenidate twice daily or three times daily at doses of 10 to 60 mg/day is

provided in Table 2. Dosing recommendations are based on current dose regimen and clinical judgment.

Conversion dosage should not exceed 72 mg daily.

TABLE 2. Recommended Dose Conversion from Methylphenidate Regimens to methylphenidate

hydrochloride extended-release tablets

Previous Methylphenidate Daily

Dos e

Recommended methylphenidate hydrochloride extended-

release tablets Starting Dose

5 mg Methylphenidate twice daily or

three times daily

18 mg every morning

10 mg Methylphenidate twice daily or

three times daily

36 mg every morning

15 mg Methylphenidate twice daily or

three times daily

54 mg every morning

20 mg Methylphenidate twice daily or

three times daily

72 mg every morning

Other methylphenidate regimens: Clinical judgment should be used when selecting the starting dose.

2.4 Dose Titration

Doses may be increased in 18 mg increments at weekly intervals for patients who have not achieved an

optimal response at a lower dose. Daily dosages above 54 mg in children and 72 mg in adolescents have

not been studied and are not recommended. Daily dosages above 72 mg in adults are not recommended.

A 27 mg dosage strength is available for physicians who wish to prescribe between the 18 mg and 36

mg dosages.

2.5 Maintenance/Extended Treatment

There is no body of evidence available from controlled trials to indicate how long the patient with

ADHD should be treated with methylphenidate hydrochloride extended-release tablets. It is generally

agreed, however, that pharmacological treatment of ADHD may be needed for extended periods.

The effectiveness of methylphenidate hydrochloride extended-release tablets for long-term use, i.e.,

for more than 7 weeks, has not been systematically evaluated in controlled trials. The physician who

elects to use methylphenidate hydrochloride extended-release tablets for extended periods in patients

with ADHD should periodically re-evaluate the long-term usefulness of the drug for the individual

patient with trials off medication to assess the patient's functioning without pharmacotherapy.

Improvement may be sustained when the drug is either temporarily or permanently discontinued.

2.6 Dose Reduction and Discontinuation

If paradoxical aggravation of symptoms or other adverse events occur, the dosage should be reduced,

or, if necessary, the drug should be discontinued.

If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug

should be discontinued.

3 DOSAGE FORMS AND STRENGTHS

Methylphenidate hydrochloride extended-release tablets are available in the following dosage

strengths: 18 mg tablets are yellow with “TL706” imprinted in black ink, 27 mg tablets are gray with

“TL707” imprinted in black ink, 36 mg tablets are white with “TL708” imprinted in black ink, 54 mg

tablets are pink with “TL709" imprinted in black ink, and 72 mg tablets are blue with “TL710” imprinted

in black ink.

4 CONTRAINDICATIONS

4.1 Hypersensitivity to Methylphenidate

Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been observed in

patients treated with methylphenidate hydrochloride extended-release tablets. Therefore,

methylphenidate hydrochloride extended-release tablets are contraindicated in patients known to be

hypersensitive to methylphenidate or other components of the product [see Adverse Reactions (6.6)].

4.2 Agitation

Methylphenidate hydrochloride extended-release tablets are contraindicated in patients with marked

anxiety, tension, and agitation, since the drug may aggravate these symptoms.

4.3 Glaucoma

Methylphenidate hydrochloride extended-release tablets are contraindicated in patients with glaucoma.

4.4 Tics

Methylphenidate hydrochloride extended-release tablets are contraindicated in patients with motor tics

or with a family history or diagnosis of Tourette's syndrome [see Adverse Reactions (6.4)].

4.5 Monoamine Oxidase Inhibitors

Methylphenidate hydrochloride extended-release tablets are contraindicated during treatment with

monoamine oxidase (MAO) inhibitors, and also within a minimum of 14 days following discontinuation

of a MAO inhibitor (hypertensive crises may result) [see Drug Interactions (7.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Serious Cardiovascular Events

Sudden Death and Preexisting Structural Cardiac Abnormalities or Other Serious Heart Problems

Children and Adolescents

Sudden death has been reported in association with CNS stimulant treatment at usual doses in children

and adolescents with structural cardiac abnormalities or other serious heart problems. Although some

serious heart problems alone carry an increased risk of sudden death, stimulant products generally

should not be used in children or adolescents with known serious structural cardiac abnormalities,

cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place

them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

Adults

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at

usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults

have a greater likelihood than children of having serious structural cardiac abnormalities,

cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac

problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.

Hypertension and Other Cardiovascular Conditions

Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mm Hg) and

average heart rate (about 3 to 6 bpm) [see Adverse Reactions (6.5)], and individuals may have larger

increases. While the mean changes alone would not be expected to have short-term consequences, all

patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in

treating patients whose underlying medical conditions might be compromised by increases in blood

pressure or heart rate, e.g., those with preexisting hypertension, heart failure, recent myocardial

infarction, or ventricular arrhythmia.

Assessing Cardiovascular Status in Patients Being Treated with Stimulant Medications

Children, adolescents, or adults who are being considered for treatment with stimulant medications

should have a careful history (including assessment for a family history of sudden death or ventricular

arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further

cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram).

Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms

suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.

5.2 Psychiatric Adverse Events

Preexisting Psychosis

Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in

patients with a preexisting psychotic disorder.

Bipolar Illness

Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar

disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to

initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately

screened to determine if they are at 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 Symptoms

Treatment-emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in

patients without a 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, and

discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-

controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3482 exposed

to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients

compared to 0 in placebo-treated patients.

Aggression

Aggressive behavior or hostility is often observed in patients with ADHD, and has been reported in

clinical trials and the postmarketing experience of some medications indicated for the treatment of

ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility,

patients beginning treatment for ADHD should be monitored for the appearance of or worsening of

aggressive behavior or hostility.

5.3 Seizures

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with

prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very

rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence

of seizures, the drug should be discontinued.

5.4 Priapism

Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with

methylphenidate products, including methylphenidate hydrochloride extended release tablets, in both

pediatric and adult patients [see Adverse Reactions (6.6)]. 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.

5.5 Peripheral Vasculopathy, including Raynaud's Phenomenon

Stimulants, including methylphenidate hydrochloride extended release tablets, 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.

5.6 Long-Term Suppression of Growth

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either

methylphenidate or nonmedication treatment groups over 14 months, as well as in naturalistic subgroups

of newly methylphenidate-treated and nonmedication-treated children over 36 months (to the ages of 10

to 13 years), suggests that consistently medicated children (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. Published data are inadequate to determine whether chronic use of

amphetamines may cause similar suppression of growth; 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 not growing or gaining height or weight as expected may need to have their treatment

interrupted.

5.7 Visual Disturbance

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

5.8 Potential for Gastrointestinal Obstruction

Because the methylphenidate hydrochloride extended-release tablet is nondeformable and does not

appreciably change in shape in the GI tract, methylphenidate hydrochloride extended-release

tablets should not ordinarily be administered to patients with preexisting severe gastrointestinal

narrowing (pathologic or iatrogenic, for example: esophageal motility disorders, small bowel

inflammatory disease, "short gut" syndrome due to adhesions or decreased transit time, past history of

peritonitis, cystic fibrosis, chronic intestinal pseudoobstruction, or Meckel's diverticulum). There have

been rare reports of obstructive symptoms in patients with known strictures in association with the

ingestion of drugs in nondeformable controlled-release formulations. Due to the controlled-release

design of the tablet, methylphenidate hydrochloride extended-release tablets should be used only in

patients who are able to swallow the tablet whole [see Patient Counseling Information (17)].

5.9 Hematologic Monitoring

Periodic CBC, differential, and platelet counts are advised during prolonged therapy.

6 ADVERSE REACTIONS

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

Drug Dependence [see Box Warning]

Hypersensitivity to Methylphenidate [see Contraindications (4.1)]

Agitation [see Contraindications (4.2)]

Glaucoma [see Contraindications (4.3)]

Tics [see Contraindications (4.4)]

Monoamine Oxidase Inhibitors [see Contraindications (4.5) and Drug Interactions (7.1)]

Serious Cardiovascular Events [see Warnings and Precautions (5.1)]

Psychiatric Adverse Events [see Warnings and Precautions (5.2)]

Seizures [see Warnings and Precautions (5.3)]

Priapism [see Warnings and Precautions (5.4)]

Long-Term Suppression of Growth [see Warnings and Precautions (5.6)]

Visual Disturbance [see Warnings and Precautions (5.7)]

Potential for Gastrointestinal Obstruction [see Warnings and Precautions (5.8)]

Hematologic Monitoring [see Warnings and Precautions (5.9)]

The most common adverse reaction in double-blind clinical trials (>5%) in pediatric patients (children

and adolescents) was abdominal pain upper. The most common adverse reactions in double-blind

clinical trials (>5%) in adult patients were decreased appetite, headache, dry mouth, nausea, insomnia,

anxiety, dizziness, weight decreased, irritability, and hyperhidrosis [see Adverse Reactions (6.1)].

The most common adverse reactions associated with discontinuation (≥1%) from either pediatric or

adult clinical trials were anxiety, irritability, insomnia, and blood pressure increased [see Adverse

Reactions (6.3)].

The development program for methylphenidate hydrochloride extended-release tablets included

exposures in a total of 3906 participants in clinical trials. Children, adolescents, and adults with ADHD

were evaluated in 6 controlled clinical studies and 11 open-label clinical studies (see Table 3). Safety

was assessed by collecting adverse events, vital signs, weights, and ECGs, and by performing physical

examinations and laboratory analyses.

Table 3. Methylphenidate hydrochloride extended-release tablets Exposure in Double-Blind and

Open-Label Clinical Studies

Patient Population

N

Dose Range

Children

2216 18 to 54 mg once daily

Adolescents

18 to 72 mg once daily

Adults

1188 18 to 108 mg once daily

Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical

investigators using their own terminology. Consequently, to provide a meaningful estimate of the

proportion of individuals experiencing adverse events, events were grouped in standardized categories

using MedDRA terminology.

The stated frequencies of adverse events represent the proportion of individuals who experienced, at

least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-

emergent if it occurred for the first time or worsened while receiving therapy following baseline

evaluation.

Throughout this section, adverse reactions are reported. Adverse reactions are adverse events that

were considered to be reasonably associated with the use of methylphenidate hydrochloride extended-

release tablets based on the comprehensive assessment of the available adverse event information. A

causal association for methylphenidate hydrochloride extended-release tablets often cannot be reliably

established in individual cases. Further, 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 clinical trials of another drug and may not reflect the rates observed in clinical practice.

The majority of adverse reactions were mild to moderate in severity.

6.1 Commonly Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials

Adverse reactions in either the pediatric or adult double-blind adverse reactions tables may be relevant

for both patient populations.

Children and Adolescents

Table 4 lists the adverse reactions reported in 1% or more of methylphenidate hydrochloride extended-

release tablets-treated children and adolescent subjects in 4 placebo-controlled, double-blind clinical

trials.

Table 4. Adverse Reactions Reported by ≥1% of methylphenidate hydrochloride extended-

release tablets-Treated Children and Adolescent Subjects in 4 Placebo-Controlled, Double-Blind

Clinical Trials of methylphenidate hydrochloride extended-release tablets

System/Organ Class

Adverse Reaction

methylphenidate hydrochloride extended-

release tablets

(n=321)

%

Placebo

(n=318)

%

Gastrointestinal Disorders

Abdominal pain upper

Vomiting

General Disorders and Administration Site

Conditions

Pyrexia

Infections and Infestations

Nasopharyngitis

Nervous System Disorders

Dizziness

Psychiatric Disorders

Insomnia

Respiratory, Thoracic and Mediastinal

Dis orders

Cough

Oropharyngeal pain

The majority of adverse reactions were mild to moderate in severity.

Adults

Table 5 lists the adverse reactions reported in 1% or more of methylphenidate hydrochloride extended-

release tablets-treated adults in 2 placebo-controlled, double-blind clinical trials.

Table 5. Adverse Reactions Reported by ≥1% of methylphenidate hydrochloride extended-

release tablets-Treated Adult Subjects in 2 Placebo-Controlled, Double-Blind Clinical Trials*

System/Organ Class

Adverse Reaction

methylphenidate hydrochloride extended-

release tablets

(n=415)

%

Placebo

(n=212)

%

Cardiac Disorders

Tachycardia

Palpitations

Ear and Labyrinth Disorders

Vertigo

Eye Disorders

Vision blurred

Gastrointestinal Disorders

Dry mouth

14.0

Nausea

12.8

Dyspepsia

Vomiting

Constipation

General Disorders and Administration Site

Conditions

Irritability

Infections and Infestations

Upper respiratory tract infection

Investigations

Weight decreased

Metabolism and Nutrition Disorders

Decreased appetite

25.3

Anorexia

Musculoskeletal and Connective Tissue Disorders

Muscle tightness

Nervous System Disorders

Headache

22.2

15.6

Terms of Initial insomnia (methylphenidate hydrochloride extended-release tablets=0.6%) and Insomnia

(methylphenidate hydrochloride extended-release tablets=2.2%) are combined into Insomnia.

Dizziness

Tremor

Paresthesia

Sedation

Tension headache

Psychiatric Disorders

Insomnia

12.3

Anxiety

Initial insomnia

Depressed mood

Nervousness

Restlessness

Agitation

Aggression

Bruxism

Depression

Libido decreased

Affect lability

Confusional state

Tension

Respiratory, Thoracic and Mediastinal Disorders

Oropharyngeal pain

Skin and Subcutaneous Tissue Disorders

Hyperhidrosis

The majority of ADRs were mild to moderate in severity.

6.2 Other Adverse Reactions Observed in methylphenidate hydrochloride extended-release

tablets Clinical Trials

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.

This section includes adverse reactions reported by methylphenidate hydrochloride extended-release

tablets-treated subjects in double-blind trials that do not meet the criteria specified for Table 4 or Table

5 and all adverse reactions reported by methylphenidate hydrochloride extended-release tablets-treated

subjects who participated in open-label and postmarketing clinical trials.

Blood and Lymphatic System Disorders: Leukopenia

Eye Disorders: Accommodation disorder, Dry eye

Vascular Disorders: Hot flush

Gastrointestinal Disorders: Abdominal discomfort, Abdominal pain, Diarrhea

General Disorders and Administrative Site Conditions: Asthenia, Fatigue, Feeling jittery, Thirst

Infections and Infestations: Sinusitis

Investigations: Alanine aminotransferase increased, Blood pressure increased, Cardiac murmur, Heart

rate increased

Musculoskeletal and Connective Tissue Disorders: Muscle spasms

Nervous System Disorders: Lethargy, Psychomotor hyperactivity, Somnolence

Psychiatric Disorders: Anger, Hypervigilance, Mood altered, Mood swings, Panic attack, Sleep

disorder, Tearfulness, Tic

Reproductive System and Breast Disorders: Erectile dysfunction

Respiratory, Thoracic and Mediastinal Disorders: Dyspnea

Skin and Subcutaneous Tissue Disorders: Rash, Rash macular

Vascular Disorders: Hypertension

6.3 Discontinuation Due to Adverse Reactions

Adverse reactions in the 4 placebo-controlled studies of children and adolescents leading to

discontinuation occurred in 2 methylphenidate hydrochloride extended-release tablets patients (0.6%)

including depressed mood (1, 0.3%) and headache and insomnia (1, 0.3%), and 6 placebo patients (1.9%)

including headache and insomnia (1, 0.3%), irritability (2, 0.6%), headache (1, 0.3%), psychomotor

hyperactivity (1, 0.3%), and tic (1, 0.3%).

In the 2 placebo-controlled studies of adults, 25 methylphenidate hydrochloride extended-release

tablets patients (6.0%) and 6 placebo patients (2.8%) discontinued due to an adverse reaction. Those

events with an incidence of >0.5% in the methylphenidate hydrochloride extended-release

tablets patients included anxiety (1.7%), irritability (1.4%), blood pressure increased (1.0%), and

nervousness (0.7%). In placebo patients, blood pressure increased and depressed mood had an incidence

of >0.5% (0.9%).

In the 11 open-label studies of children, adolescents, and adults, 266 methylphenidate hydrochloride

extended-release tablets patients (7.0%) discontinued due to an adverse reaction. Those events with an

incidence of >0.5% included insomnia (1.2%), irritability (0.8%), anxiety (0.7%), decreased appetite

(0.7%), and tic (0.6%).

6.4 Tics

In a long-term uncontrolled study (n=432 children), the cumulative incidence of new onset of tics was

9% after 27 months of treatment with methylphenidate hydrochloride extended-release tablets.

In a second uncontrolled study (n=682 children) the cumulative incidence of new-onset tics was 1%

(9/682 children). The treatment period was up to 9 months with mean treatment duration of 7.2 months.

6.5 Blood Pressure and Heart Rate Increases

In the laboratory classroom clinical trials in children (Studies 1 and 2), both methylphenidate

hydrochloride extended-release tablets once daily and methylphenidate three times daily increased

resting pulse by an average of 2 to 6 bpm and produced average increases of systolic and diastolic

blood pressure of roughly 1 to 4 mm Hg during the day, relative to placebo. In the placebo-controlled

adolescent trial (Study 4), mean increases from baseline in resting pulse rate were observed with

methylphenidate hydrochloride extended-release tablets and placebo at the end of the double-blind

phase (5 and 3 beats/minute, respectively). Mean increases from baseline in blood pressure at the end of

the double-blind phase for methylphenidate hydrochloride extended-release tablets and placebo-treated

patients were 0.7 and 0.7 mm Hg (systolic) and 2.6 and 1.4 mm Hg (diastolic), respectively. In one

placebo-controlled study in adults (Study 6), dose-dependent mean increases of 3.9 to 9.8 bpm from

baseline in standing pulse rate were observed with methylphenidate hydrochloride extended-release

tablets at the end of the double-blind treatment vs. an increase of 2.7 beats/minute with placebo. Mean

changes from baseline in standing blood pressure at the end of double-blind treatment ranged from 0.1

to 2.2 mm Hg (systolic) and -0.7 to 2.2 mm Hg (diastolic) for methylphenidate hydrochloride extended-

release tablets and was 1.1 mm Hg (systolic) and -1.8 mm Hg (diastolic) for placebo. In a second

placebo-controlled study in adults (Study 5), mean changes from baseline in resting pulse rate were

observed for methylphenidate hydrochloride extended-release tablets and placebo at the end of the

double-blind treatment (3.6 and –1.6 beats/minute, respectively). Mean changes from baseline in blood

pressure at the end of the double–blind treatment for methylphenidate hydrochloride extended-release

tablets and placebo-treated patients were –1.2 and –0.5 mm Hg (systolic) and 1.1 and 0.4 mm Hg

(diastolic), respectively [see Warnings and Precautions (5.1)].

6.6 Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of

methylphenidate hydrochloride extended-release tablets. Because these reactions are reported

voluntarily from a population of uncertain size, it is not always possible to reliably estimate their

frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders: Pancytopenia, Thrombocytopenia, Thrombocytopenic purpura

Cardiac Disorders: Angina pectoris, Bradycardia, Extrasystoles, Supraventricular tachycardia,

Ventricular extrasystoles

Eye Disorders: Diplopia, Mydriasis, Visual impairment

General Disorders: Chest pain, Chest discomfort, Drug effect decreased, Hyperpyrexia, Therapeutic

response decreased

Hepatobiliary Disorders: Hepatocellular injury, Acute hepatic failure

Immune System Disorders: Hypersensitivity reactions such as Angioedema, Anaphylactic reactions,

Auricular swelling, Bullous conditions, Exfoliative conditions, Urticarias, Pruritus NEC, Rashes,

Eruptions, and Exanthemas NEC

Investigations: Blood alkaline phosphatase increased, Blood bilirubin increased, Hepatic enzyme

increased, Platelet count decreased, White blood cell count abnormal

Musculoskeletal, Connective Tissue and Bone Disorders: Arthralgia, Myalgia, Muscle twitching,

Rhabdomyolysis

Nervous System Disorders: Convulsion, Grand mal convulsion, Dyskinesia, Serotonin syndrome in

combination with serotonergic drugs

Psychiatric Disorders: Disorientation, Hallucination, Hallucination auditory, Hallucination visual,

Mania, Logorrhea, Libido changes

Reproductive System and Breast Disorders: Priapism

Skin and Subcutaneous Tissue Disorders: Alopecia, Erythema

Vascular Disorders: Raynaud's phenomenon

7 DRUG INTERACTIONS

7.1 MAO Inhibitors

Methylphenidate hydrochloride extended-release tablets should not be used in patients being treated

(currently or within the preceding 2 weeks) with MAO inhibitors [see Contraindications (4.5)].

7.2 Vasopressor Agents

Because of possible increases in blood pressure, methylphenidate hydrochloride extended-release

tablets should be used cautiously with vasopressor agents [see Warnings and Precautions (5.1)].

7.3 Coumarin Anticoagulants, Antidepressants, and Selective Serotonin Reuptake Inhibitors

Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin

anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and some antidepressants

(tricyclics and selective serotonin reuptake inhibitors). Downward dose adjustment of these drugs may

be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage

and monitor plasma drug concentrations (or, in the case of coumarin, coagulation times), when initiating

or discontinuing concomitant methylphenidate.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

Methylphenidate has been shown to have teratogenic effects in rabbits when given in doses of 200

mg/kg/day, which is approximately 100 times and 40 times the maximum recommended human dose on a

mg/kg and mg/m basis, respectively.

A reproduction study in rats revealed no evidence of harm to the fetus at oral doses up to 30 mg/kg/day,

approximately 15-fold and 3-fold the maximum recommended human dose of methylphenidate

hydrochloride extended-release tablets on a mg/kg and mg/m basis, respectively. The approximate

plasma exposure to methylphenidate plus its main metabolite PPAA in pregnant rats was 1–2 times that

seen in trials in volunteers and patients with the maximum recommended dose of methylphenidate

hydrochloride extended-release tablets based on the AUC.

The safety of methylphenidate for use during human pregnancy has not been established. There are no

adequate and well-controlled studies in pregnant women. Methylphenidate hydrochloride extended-

release tablets should be used during pregnancy only if the potential benefit justifies the potential risk to

the fetus.

8.2 Labor and Delivery

The effect of methylphenidate hydrochloride extended-release tablets on labor and delivery in humans

is unknown.

8.3 Nursing Mothers

It is not known whether methylphenidate is excreted in human milk. Because many drugs are excreted in

human milk, caution should be exercised if methylphenidate hydrochloride extended-release tablets is

administered to a nursing woman.

In lactating female rats treated with a single oral dose of 5 mg/kg radiolabeled methylphenidate,

radioactivity (representing methylphenidate and/or its metabolites) was observed in milk and levels were

generally similar to those in plasma.

8.4 Pediatric Use

Methylphenidate hydrochloride extended-release tablets should not be used in children under six years,

since safety and efficacy in this age group have not been established. Long-term effects of

methylphenidate in children have not been well established.

8.5 Geriatric Use

Methylphenidate hydrochloride extended-release tablets have not been studied in patients greater than

65 years of age.

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Methylphenidate is a Schedule II controlled substance under the Controlled Substances Act.

9.2 Abuse

As noted in the Box Warning, methylphenidate hydrochloride extended-release tablets should be given

cautiously to patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to

marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank

psychotic episodes can occur, especially with parenteral abuse.

In two placebo-controlled human abuse potential studies, single oral doses of methylphenidate

hydrochloride extended-release tablets were compared to single oral doses of immediate-release

methylphenidate (IR MPH) and placebo in subjects with a history of recreational stimulant use to assess

relative abuse potential. For the purpose of this assessment, the response for each of the subjective

measures was defined as the maximum effect within the first 8 hours after dose administration.

In one study (n=40), both methylphenidate hydrochloride extended-release tablets (108 mg) and 60 mg

IR MPH compared to placebo produced statistically significantly greater responses on the five

subjective measures suggestive of abuse potential. In comparisons between the two active treatments,

however, methylphenidate hydrochloride extended-release tablets (108 mg) produced variable

responses on positive subjective measures that were either statistically indistinguishable from (Abuse

Potential, Drug Liking, Amphetamine, and Morphine Benzedrine Group [Euphoria]) or statistically less

than (Stimulation – Euphoria) responses produced by 60 mg IR MPH.

In another study (n=49), both doses of methylphenidate hydrochloride extended-release tablets (54 mg

and 108 mg) and both doses of IR MPH (50 mg and 90 mg) produced statistically significantly greater

responses compared to placebo on the two primary scales used in the study (Drug Liking, Euphoria).

When doses of methylphenidate hydrochloride extended-release tablets (54 mg and 108 mg) were

compared to IR MPH (50 mg and 90 mg), respectively, methylphenidate hydrochloride extended-

release tablets produced statistically significantly lower subjective responses on these two scales than

IR MPH. Methylphenidate hydrochloride extended-release tablets (108 mg) produced responses that

were statistically indistinguishable from the responses on these two scales produced by IR MPH (50

mg). Differences in subjective responses to the respective doses should be considered in the context

that only 22% of the total amount of methylphenidate in methylphenidate hydrochloride extended-release

tablets is available for immediate release from the drug overcoat [see System Components and

Performance (11.1)].

Although these findings reveal a relatively lower response to methylphenidate hydrochloride extended-

release tablets on subjective measures suggestive of abuse potential compared to IR MPH at roughly

equivalent total MPH doses, the relevance of these findings to the abuse potential of methylphenidate

hydrochloride extended-release tablets in the community is unknown.

9.3 Dependence

As noted in the Box Warning, careful supervision is required during withdrawal from abusive use since

severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of

the underlying disorder that may require follow-up.

10 OVERDOSAGE

10.1 Signs and Symptoms

Signs and symptoms of methylphenidate hydrochloride extended-release tablets overdosage, resulting

principally from overstimulation of the CNS and from excessive sympathomimetic effects, may include

the following: vomiting, agitation, muscle twitching, convulsion, grand mal convulsion, confusional

state, hallucinations (auditory and/or visual), hyperhidrosis, headache, pyrexia, tachycardia, palpitations,

heart rate increased, sinus arrhythmia, hypertension, rhabdomyolysis, mydriasis, and dry mouth.

10.2 Recommended Treatment

Treatment consists of appropriate supportive measures. The patient must be protected against self-injury

and against external stimuli that would aggravate overstimulation already present. Gastric contents may

be evacuated by gastric lavage as indicated. Before performing gastric lavage, control agitation and

seizures if present and protect the airway. Other measures to detoxify the gut include administration of

activated charcoal and a cathartic. Intensive care must be provided to maintain adequate circulation and

respiratory exchange; external cooling procedures may be required for pyrexia.

Efficacy of peritoneal dialysis or extracorporeal hemodialysis for methylphenidate hydrochloride

extended-release tablets overdosage has not been established.

The prolonged release of methylphenidate from methylphenidate hydrochloride extended-release

tablets should be considered when treating patients with overdose.

10.3 Poison Control Center

As with the management of all overdosage, the possibility of multiple-drug ingestion should be

considered. The physician may wish to consider contacting a poison control center for up-to-date

information on the management of overdosage with methylphenidate.

11 DESCRIPTION

Methylphenidate hydrochloride extended-release tablets are a central nervous system (CNS) stimulant.

Methylphenidate hydrochloride extended-release tablets are available in five tablet strengths. Each

extended-release tablet for once-a-day oral administration contains 18, 27, 36, 54, or 72 mg of

methylphenidate HCl USP and is designed to have a 12-hour duration of effect. Chemically,

methylphenidate HCl is d,l (racemic) methyl α-phenyl-2-piperidineacetate hydrochloride. Its empirical

formula is C

H NO HCl. Its structural formula is:

Methylphenidate HCl USP is a white, odorless crystalline powder. Its solutions are acid to litmus. It is

freely soluble in water and in methanol, soluble in alcohol, and slightly soluble in chloroform and in

acetone. Its molecular weight is 269.77.

Methylphenidate hydrochloride extended-release tablets also contains the following inactive

ingredients: black iron oxide, cellulose acetate, colloidal silicon dioxide, ferrosoferric oxide,

hypromellose, lactose monohydrate, magnesium stearate, phosphoric acid, polyethylene glycol,

polyethylene oxide, sodium chloride, succinic acid, titanium dioxide, triacetin. In addition,

27 mg tablets contain: FD&C Yellow #6 Aluminum Lake, FD&C Blue #2 Aluminum Lake, FD&C Red

#40 Aluminum Lake

54 mg tablets contain: FD&C Yellow #6 Aluminum Lake, FD&C Red #40 Aluminum Lake, FD&C Blue

#2 Aluminum Lake

72 mg tablets contain: FD&C Blue #1 Aluminum Lake

USP Dissolution Test Pending

11.1 System Components and Performance

Methylphenidate hydrochloride extended-release tablets use osmotic pressure to deliver

methylphenidate HCl at a controlled rate. The system, which resembles a conventional tablet in

appearance, comprises an osmotically active bilayer core surrounded by a semipermeable membrane

with an immediate-release drug overcoat. The bilayer core is composed of a drug layer containing the

drug and excipients, and a push layer containing osmotically active components. There is a precision-

laser drilled orifice on the drug-layer end of the tablet. In an aqueous environment, such as the

gastrointestinal tract, the drug overcoat dissolves within one hour, providing an initial dose of

methylphenidate. Water permeates through the membrane into the tablet core. As the osmotically active

polymer excipients expand, methylphenidate is released through the orifice. The membrane controls the

rate at which water enters the tablet core, which in turn controls drug delivery. Furthermore, the drug

release rate from the system increases with time over a period of 6 to 7 hours due to the drug-

concentration gradient incorporated into the drug layer of core of methylphenidate hydrochloride

extended-release tablets. The biologically inert components of the tablet remain intact during

gastrointestinal transit and are eliminated in the stool as a tablet shell along with insoluble core

components. It is possible that methylphenidate hydrochloride extended-release tablets may be visible

on abdominal x-rays under certain circumstances, especially when digital enhancing techniques are

utilized.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Methylphenidate HCl is a central nervous system (CNS) stimulant. The mode of therapeutic action in

Attention Deficit Hyperactivity Disorder (ADHD) is not known. Methylphenidate is thought to block the

reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these

monoamines into the extraneuronal space.

12.2 Pharmacodynamics

Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more

pharmacologically active than the l-isomer.

12.3 Pharmacokinetics

Absorption

Methylphenidate is readily absorbed. Following oral administration of methylphenidate hydrochloride

extended-release tablets, plasma methylphenidate concentrations increase rapidly, reaching an initial

maximum at about 1 hour, followed by gradual ascending concentrations over the next 5 to 9 hours, after

which a gradual decrease begins. Mean times to reach peak plasma concentrations across all doses of

methylphenidate hydrochloride extended-release tablets occurred between 6 and 10 hours.

Methylphenidate hydrochloride extended-release tablets once daily minimizes the fluctuations between

peak and trough concentrations associated with immediate-release methylphenidate three times daily

(see Figure 1). The relative bioavailability of methylphenidate hydrochloride extended-release tablets

once daily and methylphenidate three times daily in adults is comparable.

Figure 1. Mean methylphenidate plasma concentrations in 36 adults, following a single dose of

methylphenidate hydrochloride extended-release tablets 18 mg once daily and immediate-release

methylphenidate 5 mg three times daily administered every 4 hours.

The mean single-dose pharmacokinetic parameters in 36 healthy adults following the administration of

methylphenidate hydrochloride extended-release tablets 18 mg once daily and methylphenidate 5 mg

three times daily are summarized in Table 6.

TABLE 6. Pharmacokinetic Parameters (Mean ± SD) After Single Dose in Healthy Adults

Parameters

methylphenidate hydrochloride extended-release tablets

(18 mg once daily)

(n=36)

methylphenidate

(5 mg three times daily)

(n=35)

(ng/mL)

3.7 ± 1.0

4.2 ± 1.0

6.8 ± 1.8

6.5 ± 1.8

(ng·h/mL) 41.8 ± 13.9

38.0 ± 11.0

3.5 ± 0.4

3.0 ± 0.5

The pharmacokinetics of methylphenidate hydrochloride extended-release tablets were evaluated in

healthy adults following single- and multiple-dose administration (steady state) of doses up to 144

mg/day. The mean half-life was about 3.6 hours. No differences in the pharmacokinetics of

methylphenidate hydrochloride extended-release tablets were noted following single and repeated

once-daily dosing, indicating no significant drug accumulation. The AUC and t

following repeated

once-daily dosing are similar to those following the first dose of methylphenidate hydrochloride

extended-release tablets in a dose range of 18 to 144 mg.

Dose Proportionality

Following administration methylphenidate hydrochloride extended-release tablets in single doses of 18,

36, and 54 mg/day to healthy adults, C

and AUC

of d-methylphenidate were proportional to

dose, whereas l-methylphenidate C

and AUC

increased disproportionately with respect to

dose. Following administration of methylphenidate hydrochloride extended-release tablets, plasma

concentrations of the l-isomer were approximately 1/40 the plasma concentrations of the d-isomer.

(0–inf)

(0–inf)

In healthy adults, single and multiple dosing of once-daily methylphenidate hydrochloride extended-

release tablets doses from 54 to 144 mg/day resulted in linear and dose-proportional increases in C

and AUC

for total methylphenidate (MPH) and its major metabolite, α-phenyl-piperidine acetic acid

(PPAA). There was no time dependency in the pharmacokinetics of methylphenidate. The ratio of

metabolite (PPAA) to parent drug (MPH) was constant across doses from 54 to 144 mg/day, both after

single dose and upon multiple dosing.

In a multiple-dose study in adolescent ADHD patients aged 13 to 16 administered their prescribed dose

(18 to 72 mg/day) of methylphenidate hydrochloride extended-release tablets, mean C

and AUC

of d- and total methylphenidate increased proportionally with respect to dose.

Distribution

Plasma methylphenidate concentrations in adults and adolescents decline biexponentially following oral

administration. The half-life of methylphenidate in adults and adolescents following oral administration

of methylphenidate hydrochloride extended-release tablets was approximately 3.5 hours.

Metabolism and Excretion

In humans, methylphenidate is metabolized primarily by de-esterification to PPAA, which has little or no

pharmacologic activity. In adults the metabolism of methylphenidate hydrochloride extended-release

tablets once daily as evaluated by metabolism to PPAA is similar to that of methylphenidate three times

daily. The metabolism of single and repeated once-daily doses of methylphenidate hydrochloride

extended-release tablets is similar.

After oral dosing of radiolabeled methylphenidate in humans, about 90% of the radioactivity was

recovered in urine. The main urinary metabolite was PPAA, accounting for approximately 80% of the

dose.

Food Effects

In patients, there were no differences in either the pharmacokinetics or the pharmacodynamic

performance of methylphenidate hydrochloride extended-release tablets when administered after a

high-fat breakfast. There is no evidence of dose dumping in the presence or absence of food.

Alcohol Effect

In-vitro studies were conducted to explore the effect of alcohol on the release characteristics of

methylphenidate for all five strengths of Methylphenidate Extended Release Tablets. At alcohol

concentrations up to 40%, there was no increased release of methylphenidate in the first two hours.

Special Populations

Gender

In healthy adults, the mean dose-adjusted AUC

values for methylphenidate hydrochloride

extended-release tablets were 36.7 ng·h/mL in men and 37.1 ng·h/mL in women, with no differences

noted between the two groups.

Race

In adults receiving methylphenidate hydrochloride extended-release tablets, dose-adjusted AUC

was consistent across ethnic groups; however, the sample size may have been insufficient to detect

ethnic variations in pharmacokinetics.

Age

Increase in age resulted in increased apparent oral clearance (CL/F) (58% increase in adolescents

compared to children). Some of these differences could be explained by body-weight differences

among these populations. This suggests that subjects with higher body weight may have lower

exposures of total methylphenidate at similar doses.

(0–inf)

(0–inf)

The pharmacokinetics of methylphenidate hydrochloride extended-release tablets have not been studied

in children less than 6 years of age.

Renal Insufficiency

There is no experience with the use of methylphenidate hydrochloride extended-release tablets in

patients with renal insufficiency. After oral administration of radiolabeled methylphenidate in humans,

methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted

in the urine in the form of PPAA. Since renal clearance is not an important route of methylphenidate

clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of

methylphenidate hydrochloride extended-release tablets.

Hepatic Insufficiency

There is no experience with the use of methylphenidate hydrochloride extended-release tablets in

patients with hepatic insufficiency.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

Carcinogenesis

In a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in

hepatocellular adenomas and, in males only, an increase in hepatoblastomas at a daily dose of

approximately 60 mg/kg/day. This dose is approximately 30 times and 4 times the maximum

recommended human dose of methylphenidate hydrochloride extended-release tablets on a mg/kg and

mg/m basis, respectively. Hepatoblastoma is a relatively rare rodent malignant tumor type. There was

no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of

hepatic tumors, and the significance of these results to humans is unknown.

Methylphenidate did not cause any increases in tumors in a lifetime carcinogenicity study carried out in

F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 22 times and

5 times the maximum recommended human dose of methylphenidate hydrochloride extended-release

tablets on a mg/kg and mg/m basis, respectively.

In a 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which is sensitive to

genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets

containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; the high-

dose groups were exposed to 60 to 74 mg/kg/day of methylphenidate.

Mutagenesis

Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or the in vitro mouse

lymphoma cell forward mutation assay. Sister chromatid exchanges and chromosome aberrations were

increased, indicative of a weak clastogenic response, in an in vitro assay in cultured Chinese Hamster

Ovary cells. Methylphenidate was negative in vivo in males and females in the mouse bone marrow

micronucleus assay.

Impairment of Fertility

Methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in

an 18-week Continuous Breeding study. The study was conducted at doses up to 160 mg/kg/day,

approximately 80-fold and 8-fold the highest recommended human dose of methylphenidate

hydrochloride extended-release tablets on a mg/kg and mg/m basis, respectively.

14 CLINICAL STUDIES

Methylphenidate hydrochloride extended-release tablets was demonstrated to be effective in the

treatment of Attention Deficit Hyperactivity Disorder (ADHD) in 4 randomized, double-blind, placebo-

controlled studies in children and adolescents and 2 double-blind placebo-controlled studies in adults

who met the Diagnostic and Statistical Manual 4

edition (DSM-IV) criteria for ADHD.

14.1 Children

Three double-blind, active- and placebo-controlled studies were conducted in 416 children aged 6 to

12 years. The controlled studies compared methylphenidate hydrochloride extended-release

tablets given once daily (18, 36, or 54 mg), methylphenidate given three times daily over 12 hours (15,

30, or 45 mg total daily dose), and placebo in two single-center, 3-week crossover studies (Studies 1

and 2) and in a multicenter, 4-week, parallel-group comparison (Study 3). The primary comparison of

interest in all three trials was methylphenidate hydrochloride extended-release tablets versus placebo.

Symptoms of ADHD were evaluated by community schoolteachers using the Inattention / Overactivity

with Aggression (IOWA) Conners scale. Statistically significant reduction in the Inattention /

Overactivity subscale versus placebo was shown consistently across all three controlled studies for

methylphenidate hydrochloride extended-release tablets. The scores for methylphenidate

hydrochloride extended-release tablets and placebo for the three studies are presented in Figure 2.

Figure 2: Mean Community School Teacher IOWA Conners Inattention/Overactivity Scores with

methylphenidate hydrochloride extended-release tablets once daily (18, 36, or 54 mg) and placebo.

Studies 1 and 2 involved a 3-way crossover of 1 week per treatment arm. Study 3 involved 4 weeks of

parallel-group treatments with a Last Observation Carried Forward analysis at week 4. Error bars

represent the mean plus standard error of the mean.

In Studies 1 and 2, symptoms of ADHD were evaluated by laboratory schoolteachers using the

SKAMP laboratory school rating scale. The combined results from these two studies demonstrated

statistically significant improvements in attention and behavior in patients treated with methylphenidate

hydrochloride extended-release tablets versus placebo that were maintained through 12 hours after

dosing. Figure 3 presents the laboratory schoolteacher SKAMP ratings for methylphenidate

hydrochloride extended-release tablets and placebo.

Figure 3: Laboratory School Teacher SKAMP Ratings: Mean (SEM) of Combined Attention (Studies 1

and 2)

14.2 Adolescents

In a randomized, double-blind, multicenter, placebo-controlled trial (Study 4) involving 177 patients,

methylphenidate hydrochloride extended-release tablets was demonstrated to be effective in the

treatment of ADHD in adolescents aged 13 to 18 years at doses up to 72 mg/day (1.4 mg/kg/day). Of 220

patients who entered an open 4-week titration phase, 177 were titrated to an individualized dose

(maximum of 72 mg/day) based on meeting specific improvement criteria on the ADHD Rating Scale and

the Global Assessment of Effectiveness with acceptable tolerability. Patients who met these criteria

were then randomized to receive either their individualized dose of methylphenidate hydrochloride

extended-release tablets (18 – 72 mg/day, n=87) or placebo (n=90) during a two-week double-blind

phase. At the end of this phase, mean scores for the investigator rating on the ADHD Rating Scale

demonstrated that methylphenidate hydrochloride extended-release tablets was statistically significantly

Swanson, Kotkin, Agler, M-Fynn, and Pelham

superior to placebo.

14.3 Adults

Two double-blind, placebo-controlled studies were conducted in 627 adults aged 18 to 65 years. The

controlled studies compared methylphenidate hydrochloride extended-release tablets administered once

daily and placebo in a multicenter, parallel-group, 7-week dose-titration study (Study 5) (36 to 108

mg/day) and in a multicenter, parallel-group, 5-week, fixed-dose study (Study 6) (18, 36, and 72 mg/day).

Study 5 demonstrated the effectiveness of methylphenidate hydrochloride extended-release tablets in

the treatment of ADHD in adults aged 18 to 65 years at doses from 36 mg/day to 108 mg/day based on

the change from baseline to final study visit on the Adult ADHD Investigator Rating Scale (AISRS). Of

226 patients who entered the 7-week trial, 110 were randomized to methylphenidate hydrochloride

extended-release tablets and 116 were randomized to placebo. Treatment was initiated at 36 mg/day and

patients continued with incremental increases of 18 mg/day (36 to 108 mg/day) based on meeting

specific improvement criteria with acceptable tolerability. At the final study visit, mean change scores

(LS Mean, SEM) for the investigator rating on the AISRS demonstrated that methylphenidate

hydrochloride extended-release tablets was statistically significantly superior to placebo.

Study 6 was a multicenter, double-blind, randomized, placebo-controlled, parallel-group, dose-

response study (5-week duration) with 3 fixed-dose groups (18, 36, and 72 mg). Patients were

randomized to receive methylphenidate hydrochloride extended-release tablets administered at doses of

18 mg (n=101), 36 mg (n=102), 72 mg/day (n=102), or placebo (n=96). All three doses of

methylphenidate hydrochloride extended-release tablets were statistically significantly more effective

than placebo in improving CAARS (Conners' Adult ADHD Rating Scale) total scores at double-blind

end point in adult subjects with ADHD.

15 REFERENCES

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed.

Washington, DC: American Psychiatric Association, 1994.

16 HOW SUPPLIED/STORAGE AND HANDLING

Methylphenidate hydrochloride extended-release tablets are available in 18, 27, 36, 54, and 72 mg

strengths. The 18 mg tablets are yellow with “TL706” imprinted in black ink, 27 mg tablets are gray

with “TL707” imprinted in black ink, 36 mg tablets are white with “TL708” imprinted in black ink, 54 mg

tablets are pink with “TL709" imprinted in black ink, and 72 mg tablets are blue with “TL710” imprinted

in black ink.

The tablets are supplied:

18 mg

100-count

bottle

NDC 13811-706-

27 mg

100-count bottle

NDC 13811-707-

36 mg

100-count bottle

NDC 13811-708-

54 mg

100-count bottle

NDC 13811-709-

72 mg

30-count bottle

NDC 13811-710-

72 mg

100-count bottle

NDC 13811-710-

Storage and Handling

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room

Temperature]. Protect from humidity.

17 PATIENT COUNSELING INFORMATION

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

Priapism

Advise patients, caregivers, and family members of the possibility of painful or prolonged penile

erections (priapism). Instruct the patient to seek immediate medical attention in the event of

priapism [see Warnings and Precautions (5.4)].

Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, including Raynaud’s Phenomenon]

Instruct patients beginning treatment with methylphenidate hydrochloride extended release tablets about

the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and

symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to

red.

Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to

temperature in fingers or toes.

Instruct patients to call their physician immediately with any signs of unexplained wounds

appearing on fingers or toes while taking methylphenidate hydrochloride extended release

tablets .

Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

General Considerations

Prescribers or other health professionals should inform patients, their families, and their caregivers

about the benefits and risks associated with treatment with methylphenidate and should counsel them in

its appropriate use. A patient Medication Guide is available for methylphenidate hydrochloride

extended-release tablets. The prescriber or health professional should instruct patients, their families,

and their caregivers to read the Medication Guide and should assist them in understanding its contents.

Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain

answers to any questions they may have.

Administration Instructions

Patients should be informed that methylphenidate hydrochloride extended-release tablets should be

swallowed whole with the aid of liquids. Tablets should not be chewed, divided, or crushed. The

medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate.

The tablet shell, along with insoluble core components, is eliminated from the body; patients should not

be concerned if they occasionally notice in their stool something that looks like a tablet.

Driving or Operating Heavy Machinery

Stimulants may impair the ability of the patient to operate potentially hazardous machinery or vehicles.

Patients should be cautioned accordingly until they are reasonably certain that methylphenidate

hydrochloride extended-release tablets do not adversely affect their ability to engage in such activities.

Trigen Laboratories, LLC

Bridgewater, NJ 08807

www.trigenlab.com

1-877-482-3788

200227-02

Patent numbers:

US 9,855,258

US 9,827,234

US 9,707,217

US 10,265,308 B2

MedGuide

MEDICATION GUIDE

Methylphenidate hydrochloride extended-release tablets USP CII

(METH-il-FEN-i-date)

Read the Medication Guide that comes with methylphenidate hydrochloride extended-release tablets

USP before you or your child starts taking it and each time you get a refill. There may be new

information. This Medication Guide does not take the place of talking to your doctor about your or your

child's treatment with methylphenidate hydrochloride extended-release tablets USP.

What is the most important information I should know about methylphenidate

hydrochloride extended-release tablets?

The following have been reported with use of methylphenidate HCl and other stimulant

medicines :

1. Heart-related problems:

· sudden death in patients who have heart problems or heart defects

· stroke and heart attack in adults

· increased blood pressure and heart rate

Tell your doctor if you or your child has any heart problems, heart defects, high blood pressure,

or a family history of these problems.

Your doctor should check you or your child carefully for heart problems before starting

methylphenidate hydrochloride extended-release tablets.

Your doctor should check you or your child's blood pressure and heart rate regularly during

treatment with methylphenidate hydrochloride extended-release tablets.

Call your doctor right away if you or your child has any signs of heart problems such as

chest pain, shortness of breath, or fainting while taking methylphenidate hydrochloride

extended-release tablets.

2. Mental (Psychiatric) problems:

All Patients

· new or worse behavior and thought problems

· new or worse bipolar illness

· new or worse aggressive behavior or hostility

Children and Teenagers

· new psychotic symptoms (such as hearing voices, believing things that are not true,

are suspicious) or new manic symptoms

Tell your doctor about any mental problems you or your child have, or about a family history of

suicide, bipolar illness, or depression.

Call your doctor right away if you or your child has any new or worsening mental

symptoms or problems while taking methylphenidate hydrochloride extended-release

tablets, especially seeing or hearing things that are not real, believing things that are not

real, or are suspicious.

3. Painful and prolonged erections (priapism)

Painful and prolonged erections (priapism) have occurred with methylphenidate. If you or your child

develop priapism, seek medical help right away. Because of the potential for lasting damage,

priapism should be evaluated by a doctor immediately.

4. Circulation problems in fingers and toes

[Peripheral vasculopathy, including Raynaud’s phenomenon]:

fingers or toes may feel numb, cool, painful

fingers or toes may change color from pale, to blue, to red

Tell your doctor if you have or your child has numbness, pain, skin color change, or sensitivity to

temperature in your fingers or toes.

Call your doctor right away if you have or your child has any signs of unexplained wounds

appearing on fingers or toes while taking methylphenidate hydrochloride extended release

tablets .

What is methylphenidate hydrochloride extended-release tablets?

Methylphenidate hydrochloride extended-release tablets are a central nervous system stimulant

prescription medicine. It is used for the treatment of attention deficit and hyperactivity disorder

(ADHD). Methylphenidate hydrochloride extended-release tablets may help increase attention and

decrease impulsiveness and hyperactivity in patients with ADHD.

Methylphenidate hydrochloride extended-release tablets should be used as a part of a total treatment

program for ADHD that may include counseling or other therapies.

Methylphenidate hydrochloride extended-release tablets are a federally controlled

substance (CII) because it can be abused or lead to dependence. Keep methylphenidate

hydrochloride extended-release tablets in a safe place to prevent misuse and abuse. Selling

or giving away methylphenidate hydrochloride extended-release tablets may harm others,

and is against the law.

Tell your doctor if you or your child have (or have a family history of) ever abused or been

dependent on alcohol, prescription medicines, or street drugs.

Who should not take methylphenidate hydrochloride extended-release tablets?

Methylphenidate hydrochloride extended-release tablets should not be taken if you or your child:

· is very anxious, tense, or agitated

· have an eye problem called glaucoma

· have tics or Tourette's syndrome, or a family history of Tourette's syndrome. Tics are hard-to-

control repeated movements or sounds.

· is taking or have taken within the past 14 days an antidepression medicine called a monoamine

oxidase inhibitor or MAOI.

· is allergic to anything in methylphenidate hydrochloride extended-release tablets. See the end of

this Medication Guide for a complete list of ingredients.

Methylphenidate hydrochloride extended-release tablets should not be used in children less than 6

years old because it has not been studied in this age group.

Methylphenidate hydrochloride extended-release tablets may not be right for you or your child.

Before starting methylphenidate hydrochloride extended-release tablets, tell your or your child's

doctor about all health conditions (or a family history of) including:

· heart problems, heart defects, or high blood pressure

· mental problems including psychosis, mania, bipolar illness, or depression

· tics or Tourette's syndrome

· seizures or have had an abnormal brain wave test (EEG)

· circulation problems in fingers and toes

· esophagus, stomach, or small or large intestine problems

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

Can methylphenidate hydrochloride extended-release tablets be taken with other medicines?

Tell your doctor about all of the medicines that you or your child take including prescription and

nonprescription medicines, vitamins, and herbal supplements. Methylphenidate hydrochloride

extended-release tablets and some medicines may interact with each other and cause serious side

effects. Sometimes the doses of other medicines will need to be adjusted while taking methylphenidate

hydrochloride extended-release tablets.

Your doctor will decide whether methylphenidate hydrochloride extended-release tablets can be taken

with other medicines.

Especially tell your doctor if you or your child takes:

· antidepression medicines including MAOIs

· seizure medicines

· blood thinner medicines

· blood pressure medicines

· cold or allergy medicines that contain decongestants

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

doctor and pharmacist.

Do not start any new medicine while taking methylphenidate hydrochloride extended-release

tablets without talking to your doctor first.

How should methylphenidate hydrochloride extended-release tablets be taken?

· Take methylphenidate hydrochloride extended-release tablets exactly as prescribed. Your

doctor may adjust the dose until it is right for you or your child.

· Do not chew, crush, or divide the tablets. Swallow methylphenidate hydrochloride extended-

release tablets whole with water or other liquids. Tell your doctor if you or your child cannot swallow

methylphenidate hydrochloride extended-release tablets whole. A different medicine may need to be

prescribed.

· Methylphenidate hydrochloride extended-release tablets can be taken with or without food.

· Take methylphenidate hydrochloride extended-release tablets once each day in the morning.

Methylphenidate hydrochloride extended-release tablets are an extended-release tablet. It releases

medication into your or your child's body throughout the day.

· The methylphenidate hydrochloride extended-release tablet does not dissolve completely in the

body after all the medicine has been released. You or your child may sometimes notice the empty tablet

in a bowel movement. This is normal.

· From time to time, your doctor may stop methylphenidate hydrochloride extended-release tablets

treatment for a while to check ADHD symptoms.

· Your doctor may do regular checks of the blood, heart, and blood pressure while taking

methylphenidate hydrochloride extended-release tablets. Children should have their height and weight

checked often while taking methylphenidate hydrochloride extended-release tablets. Methylphenidate

hydrochloride extended-release tablets treatment may be stopped if a problem is found during these

check-ups.

· If you or your child takes too much methylphenidate hydrochloride extended-release tablets

or overdoses, call your doctor or poison control center right away, or get emergency treatment.

What are possible side effects of methylphenidate hydrochloride extended-release tablets?

See "What is the most important information I should know about methylphenidate

hydrochloride extended-release tablets?" for information on reported 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 seizures

· eyesight changes or blurred vision

· blockage of the esophagus, stomach, small or large intestine in patients who already have a

narrowing in any of these organs

Common side effects include:

decreased appetite

dry mouth

trouble sleeping

dizziness

stomach ache

increased sweating

headache

nausea

anxiety

weight loss

irritability

Stimulants may impair the ability of you or your child to operate potentially hazardous machinery or

vehicles. You or your child should exercise caution until you or your child is reasonably certain that

methylphenidate hydrochloride extended-release tablets does not adversely affect your or your child's

ability to engage in such activities.

Talk to your doctor if you or your child has side effects that are bothersome or do not go away.

This is not a complete list of possible side effects. Ask your doctor or pharmacist for more

information.

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

FDA-1088.

You may also report side effects to Trigen Laboratories, LLC at 1-877-482-3788.

How should I store methylphenidate hydrochloride extended-release tablets?

Store methylphenidate hydrochloride extended-release tablets USP in a safe place at room temperature,

59 to 86°F (15 to 30°C). Protect from moisture.

· Keep methylphenidate hydrochloride extended-release tablets and all medicines out of the

reach of children.

General information about methylphenidate hydrochloride extended-release tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use methylphenidate hydrochloride extended-release tablets for a condition for which it was not

prescribed. Do not give methylphenidate hydrochloride extended-release tablets to other people, even

if they have the same condition. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about methylphenidate hydrochloride

extended-release tablets If you would like more information, talk with your doctor. You can ask your

doctor or pharmacist for information about methylphenidate hydrochloride extended-release tablets that

was written for healthcare professionals. For more information about methylphenidate hydrochloride

extended-release tablets call 1-877-482-3788.

What are the ingredients in methylphenidate hydrochloride extended-release tablets?

Active Ingredient: methylphenidate HCl

Inactive Ingredients: black iron oxide, cellulose acetate, colloidal silicon dioxide, ferrosoferric

oxide, hypromellose, lactose monohydrate, magnesium stearate, phosphoric acid, polyethylene glycol,

polyethylene oxide, sodium chloride, succinic acid, titanium dioxide, triacetin. In addition,

27 mg tablets contain: FD&C Yellow #6 Aluminum Lake, FD&C Blue #2 Aluminum Lake, FD&C Red

#40 Aluminum Lake

54 mg tablets contain: FD&C Yellow #6 Aluminum Lake, FD&C Red #40 Aluminum Lake, FD&C Blue

#2 Aluminum Lake

72 mg tablets contain: FD&C Blue #1 Aluminum Lake

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

Trigen Laboratories, LLC

Bridgewater, NJ 08807

www.trigenlab.com

200206-01 Rev. 11/2019

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL - Methylphenidate Hydrochloride Extended-release Tablets

CII 18 mg Tablet Label

NDC 13811-706-10

100 tablets

Rx only

Please see the Medication Guide

provided by your pharmacist.

Methylphenidate18mg 100ctRev022019

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL - Methylphenidate Hydrochloride Extended-release Tablets

CII 27 mg Tablet Label

NDC 13811-707-10

100 tablets

Rx only

Please see the Medication Guide

provided by your pharmacist.

Methylphenidate27mg 100ctRev022019

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL - Methylphenidate Hydrochloride Extended-release Tablets

CII 36 mg Tablet Label

NDC 13811-708-10

100 tablets

Rx only

Please see the Medication Guide

provided by your pharmacist.

Methylphenidate36mg 100ctRev022019

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL - Methylphenidate Hydrochloride Extended-release Tablets

CII 54 mg Tablet Label

NDC 13811-709-10

100 tablets

Rx only

Please see the Medication Guide

provided by your pharmacist.

Methylphenidate54 mg 100ctRev022019

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL - Methylphenidate Hydrochloride Extended-release Tablets

CII 72 mg Tablet Label

NDC 13811-710-10

100 tablets

Rx only

Please see the Medication Guide

provided by your pharmacist.

Methylphenidate72mg 100ctRev022019

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL - Methylphenidate Hydrochloride Extended-release Tablets

CII 72 mg Tablet Label

NDC 13811-710-30

30 tablets

Rx only

Please see the Medication Guide

provided by your pharmacist.

Methylphenidate72mg 30ctRev022019

METHYLPHENIDATE HYDROCHLORIDE

methylphenidate hydrochloride tablet, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:138 11-70 9

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

METHYLPHENIDATE HYDRO CHLO RIDE (UNII: 4B3SC438 HI) (METHYLPHENIDATE -

UNII:20 7ZZ9 QZ49 )

METHYLPHENIDATE

HYDROCHLORIDE

54 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PHO SPHO RIC ACID (UNII: E4GA8 8 8 4NN)

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

SUCCINIC ACID (UNII: AB6 MNQ6 J6 L)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

CELLULO SE ACETATE (UNII: 3J2P0 7GVB6 )

PO LYETHYLENE O XIDE 2 0 0 0 0 0 (UNII: 116 28 IH70 O)

FD&C RED NO . 4 0 (UNII: WZB9 127XOA)

FD&C BLUE NO . 2 (UNII: L0 6 K8 R7DQK)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIACETIN (UNII: XHX3C3X6 73)

FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )

PO LYETHYLENE O XIDE 50 0 0 0 0 0 (UNII: 3IG9 0 32SAH)

Product Characteristics

Color

PINK

S core

no sco re

S hap e

ROUND (capsule-shaped)

S iz e

8 mm

Flavor

Imprint Code

TL70 9

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:138 11-70 9 -10

10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /14/20 17

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 5327

0 8 /14/20 17

METHYLPHENIDATE HYDROCHLORIDE

methylphenidate hydrochloride tablet, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:138 11-70 6

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

METHYLPHENIDATE HYDRO CHLO RIDE (UNII: 4B3SC438 HI) (METHYLPHENIDATE -

UNII:20 7ZZ9 QZ49 )

METHYLPHENIDATE

HYDROCHLORIDE

18 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PHO SPHO RIC ACID (UNII: E4GA8 8 8 4NN)

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

SUCCINIC ACID (UNII: AB6 MNQ6 J6 L)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIACETIN (UNII: XHX3C3X6 73)

CELLULO SE ACETATE (UNII: 3J2P0 7GVB6 )

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

PO LYETHYLENE O XIDE 2 0 0 0 0 0 (UNII: 116 28 IH70 O)

PO LYETHYLENE O XIDE 50 0 0 0 0 0 (UNII: 3IG9 0 32SAH)

Product Characteristics

Color

YELLOW

S core

no sco re

S hap e

ROUND

S iz e

6 mm

Flavor

Imprint Code

TL70 6

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:138 11-70 6 -10

10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /14/20 17

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 5327

0 8 /14/20 17

METHYLPHENIDATE HYDROCHLORIDE

methylphenidate hydrochloride tablet, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:138 11-70 7

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

METHYLPHENIDATE HYDRO CHLO RIDE (UNII: 4B3SC438 HI) (METHYLPHENIDATE -

UNII:20 7ZZ9 QZ49 )

METHYLPHENIDATE

HYDROCHLORIDE

27 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PHO SPHO RIC ACID (UNII: E4GA8 8 8 4NN)

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

SUCCINIC ACID (UNII: AB6 MNQ6 J6 L)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIACETIN (UNII: XHX3C3X6 73)

CELLULO SE ACETATE (UNII: 3J2P0 7GVB6 )

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

FD&C BLUE NO . 2 (UNII: L0 6 K8 R7DQK)

FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )

FD&C RED NO . 4 0 (UNII: WZB9 127XOA)

PO LYETHYLENE O XIDE 2 0 0 0 0 0 (UNII: 116 28 IH70 O)

PO LYETHYLENE O XIDE 50 0 0 0 0 0 (UNII: 3IG9 0 32SAH)

Product Characteristics

Color

GRAY

S core

no sco re

S hap e

ROUND

S iz e

Flavor

Imprint Code

TL70 7

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:138 11-70 7-10

10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /14/20 17

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 5327

0 8 /14/20 17

METHYLPHENIDATE HYDROCHLORIDE

methylphenidate hydrochloride tablet, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:138 11-70 8

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

METHYLPHENIDATE HYDRO CHLO RIDE (UNII: 4B3SC438 HI) (METHYLPHENIDATE -

UNII:20 7ZZ9 QZ49 )

METHYLPHENIDATE

HYDROCHLORIDE

36 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PHO SPHO RIC ACID (UNII: E4GA8 8 8 4NN)

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

SUCCINIC ACID (UNII: AB6 MNQ6 J6 L)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIACETIN (UNII: XHX3C3X6 73)

CELLULO SE ACETATE (UNII: 3J2P0 7GVB6 )

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

PO LYETHYLENE O XIDE 2 0 0 0 0 0 (UNII: 116 28 IH70 O)

PO LYETHYLENE O XIDE 50 0 0 0 0 0 (UNII: 3IG9 0 32SAH)

Product Characteristics

Color

WHITE

S core

no sco re

S hap e

ROUND

S iz e

8 mm

Flavor

Imprint Code

TL70 8

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:138 11-70 8 -10

10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /14/20 17

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 5327

0 8 /14/20 17

METHYLPHENIDATE HYDROCHLORIDE

methylphenidate hydrochloride tablet, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:138 11-710

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

METHYLPHENIDATE HYDRO CHLO RIDE (UNII: 4B3SC438 HI) (METHYLPHENIDATE -

UNII:20 7ZZ9 QZ49 )

METHYLPHENIDATE

HYDROCHLORIDE

72 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PHO SPHO RIC ACID (UNII: E4GA8 8 8 4NN)

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

CELLULO SE ACETATE (UNII: 3J2P0 7GVB6 )

FD&C BLUE NO . 1 (UNII: H3R47K3TBD)

PO LYETHYLENE O XIDE 2 0 0 0 0 0 (UNII: 116 28 IH70 O)

SUCCINIC ACID (UNII: AB6 MNQ6 J6 L)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIACETIN (UNII: XHX3C3X6 73)

PO LYETHYLENE O XIDE 50 0 0 0 0 0 (UNII: 3IG9 0 32SAH)

Product Characteristics

Color

BLUE

S core

no sco re

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

TL710

Contains

Trigen Laboratories, LLC

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:138 11-710 -10

10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

12/29 /20 17

2

NDC:138 11-710 -30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

12/29 /20 17

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 5327

12/29 /20 17

Labeler -

T rigen Laboratories, LLC (830479668)

Revised: 11/2019

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