METADATE ER- 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:
Unither Manufacturing, LLC
INN (International Name):
methylphenidate hydrochloride
Composition:
methylphenidate hydrochloride 20 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Attention Deficit Disorders (previously known as Minimal Brain Dysfunction in Children). Other terms being used to describe the behavioral syndrome below include: Hyperkinetic Child Syndrome, Minimal Brain Damage, Minimal Cerebral Dysfunction, Minor Cerebral Dysfunction. METADATE ER is indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted. Specific etiology of th
Product summary:
METADATE ER Tablets (methylphenidate hydrochloride extended-release tablets, USP) are available as follows: 20 mg: Round, white, uncoated, unscored, debossed "562 MD".      NDC 53014-594-07   Bottle of 100's NOTE: METADATE ER Tablets are color-additive free. Dispense in a tight container as defined in the USP with a child-resistant closure. Store at 20° - 25°C (68°-77°F); excursions permitted to 15° - 30°C (59° - 86°F) [See USP Controlled Room Temperature]. Protect from moisture. Contact: Medical Affairs Department Phone: (866) 822-0068 Fax: (770) 970-8859 Manufactured for UCB, Inc. Smyrna, GA 30080 Rev. 9E 01/2014 METADATE is a registered trademark of the UCB Group of companies © 2014, UCB, Inc., Smyrna, GA 30080 All rights reserved. Printed in U.S.A.
Authorization status:
Abbreviated New Drug Application
Authorization number:
53014-594-07

METADATE ER- methylphenidate hydrochloride tablet, extended release

Unither Manufacturing, LLC

----------

MEDICATION GUIDE

METADATE® ER

(methylphenidate HCl extended-release tablets, USP) Tablets CII

Read the Medication Guide that comes with METADATE ER 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 METADATE ER.

What is the most important information I should know about METADATE ER?

The following have been reported with use of methylphenidate HCl, USP 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 have 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 METADATE

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

with METADATE ER.

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 METADATE ER.

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 have any new or worsening mental symptoms or

problems while taking METADATE ER, especially seeing or hearing things that are not real, believing

things that are not real, or are suspicious.

3. Circulation Problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon]:

fingers or toes may feel numb, cool, painful, and/or 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 the fingers and 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 METADATE ER.

What Is METADATE ER?

METADATE ER is a central nervous system stimulant prescription medicine. It is used for the treatment

of Attention-Deficit Hyperactivity Disorder (ADHD).

METADATE ER may help increase attention and decrease impulsiveness and hyperactivity in patients

with ADHD.

METADATE ER should be used as a part of a total treatment program for ADHD that may include

counseling or other therapies.

Who should not take METADATE ER?

METADATE ER should not be taken if you or your child:

are 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.

have severe high blood pressure or a heart problem

have hyperthyroidism

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

oxidase inhibitor or MAOI.

are allergic to anything in METADATE ER. See the end of this Medication Guide for a complete

list of ingredients.

METADATE ER should not be used in children less than 6 years old because it has not been studied in

this age group.

METADATE ER may not be right for you or your child. Before starting METADATE ER tell your or

your child's doctor about all health conditions (or a family history of) including:

heart problems, heart defects, 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 or toes

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

Can METADATE ER 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. METADATE ER 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 METADATE ER.

Your doctor will decide whether METADATE ER can be taken with other medicines.

Especially tell your doctor if you or your child takes:

anti-depression 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 METADATE ER without talking to your doctor first.

How should METADATE ER be taken?

Take METADATE ER exactly as prescribed. Your doctor may adjust the dose until it is right for

you or your child.

Take METADATE ER once a day. METADATE ER is an extended release tablet. It releases

medicine into your body throughout the day.

Do not chew or crush METADATE ER tablets. Swallow METADATE ER tablets whole with

water or other liquids. Tell your doctor if you or your child cannot swallow METADATE ER

whole. A different medicine may need to be prescribed.

From time to time, your doctor may stop METADATE ER treatment for a while to check ADHD

symptoms.

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

METADATE ER. Children should have their height and weight checked often while taking

METADATE ER. METADATE ER treatment may be stopped if a problem is found during these

check-ups.

If you or your child takes too much METADATE ER or overdoses, call your doctor or poison

control center right away, or get emergency treatment.

What are possible side effects of METADATE ER?

See "What is the most important information I should know about METADATE ER?" 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

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.

Common side effects include:

headache

decreased appetite

stomach ache

nervousness

trouble sleeping

dizziness

nausea

heart palpitations

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.

How should I store METADATE ER?

Store METADATE ER in a safe place at room temperature, 59 to 86° F (15 to 30° C). Protect

from moisture.

Keep METADATE ER and all medicines out of the reach of children.

General information about METADATE ER

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

use METADATE ER for a condition for which it was not prescribed. Do not give METADATE ER 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 METADATE ER. If you would

like more information, talk with your doctor. You can ask your doctor or pharmacist for information

about METADATE ER that was written for healthcare professionals. For more information about

METADATE ER call 1-866-822-0068.

What are the ingredients in METADATE ER?

Active Ingredient: methylphenidate HCl

Inactive Ingredients: cetyl alcohol, ethylcellulose, anhydrous lactose and magnesium stearate.

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

Manufactured for

UCB, Inc.

Smyrna, GA 30080

METADATE is a registered trademark of the UCB Group of companies

©2014, UCB, Inc., Smyrna, GA 30080

All rights reserved. Printed in U.S.A.

3E 01/2014

Revised: 1/2014

Document Id: 6470b9ad-04b8-4386-b2c3-184518ac6957

Set id: 739bbd64-d9e1-4771-967b-a2cd08f4eaf5

Version: 9

Effective Time: 20140106

Unither Manufacturing, LLC

METADATE ER- methylphenidate hydrochloride tablet, extended release

Unither Manufacturing, LLC

----------

Metadate

ER Tablets

(methylphenidate hydrochloride

extended-release tablets, USP)

CII

Rx Only

DESCRIPTION

METADATE ER Tablets (methylphenidate hydrochloride extended-release tablets, USP) are a mild

central nervous system (CNS) stimulant. METADATE ER is available as 20 mg extended-release

tablets for oral administration.

Methylphenidate hydrochloride is methyl α-phenyl-2-piperidineacetate hydrochloride, and its structural

formula is:

Methylphenidate hydrochloride is a white, odorless, fine crystalline powder. Its solutions are acid to

litmus. It is freely soluble in water and in methanol, soluble in alcohol, and slightly soluble in

chloroform and in acetone. Its chemical formula is C

H NO HCl, and its molecular weight is

269.77.

Inactive Ingredients: Cetyl alcohol, ethylcellulose, anhydrous lactose and magnesium stearate.

CLINICAL PHARMACOLOGY

Pharmacodynamics

METADATE ER is a mild central nervous system stimulant.

The mode of action in man is not completely understood, but methylphenidate presumably activates the

brain stem arousal system and cortex to produce its stimulant effect.

There is neither specific evidence which clearly establishes the mechanism whereby methylphenidate

produces its mental and behavioral effects in children, nor conclusive evidence regarding how these

effects relate to the condition of the central nervous system.

Effects on QT Interval

The effect of Focalin® XR (dexmethylphenidate, the pharmacologically active d-enantiomer of

methylphenidate) on the QT interval was evaluated in a double-blind, placebo- and open label active

(moxifloxacin)-controlled study following single doses of Focalin® XR 40mg in 75 healthy

volunteers. ECGs were collected up to 12 h post-dose. Frederica's method for heart rate correction

was employed to derive the corrected QT interval (QTcF). The maximum mean prolongation of QTcF

intervals was <5 ms, and the upper limit of the 90% confidence interval was below 10 ms for all time

matched comparisons versus placebo. This was below the threshold of clinical concern and there was

®

no evident-exposure response relationship.

Pharmacokinetics

METADATE ER in extended-release tablets is more slowly but as extensively absorbed as in the

regular tablets. Bioavailability of METADATE 20 mg Extended-Release Tablets was compared to a

sustained-release reference product and an immediate-release product. The extent of absorption for the

three products was similar, and the rate of absorption of the two sustained-release products was not

statistically different.

In another reported study with a brand of Methylphenidate HCl sustained-release, the time to peak rate in

children was reported as 4.7 hours (1.3 - 8.2 hours) for the sustained-release tablet dosage form and 1.9

hours (0.3 - 4.4 hours) for immediate release tablets. An average of 67% of a sustained-release tablet

dosage form was excreted in children compared to 86% in adults.

Based on rate of bioavailability (AUC

and C

), no significant statistical difference was

found following single dose administration, in fasting and fed adults, of two METADATE 10 mg

Extended-Release Tablets, or one methylphenidate hydrochloride, USP sustained-release 20 mg tablet.

The administration of the extended-release methylphenidate HCl, USP, tablets with food, resulted in a

greater C

and AUC

than when administered in a fasting condition.

Pharmacokinetic and statistical analyses for a multiple dose study demonstrated that 3 times daily

administration of two METADATE 10 mg Extended-Release Tablets met the requirements for

bioequivalence to one methylphenidate hydrochloride, USP sustained-release 20 mg tablet when

administered every eight hours. Pharmacokinetic parameters (i.e., AUC

, and C )

demonstrated achievement of steady state following 3 times daily administration of two METADATE

10 mg Extended-Release Tablets was confirmed.

In a clinical study involving adult subjects who received Extended-release (ER) tablets, plasma

concentrations of methylphenidate hydrochloride's major metabolite appeared to be greater in females

than in males. No gender differences were observed for methylphenidate hydrochloride's plasma

concentration in the same subjects.

INDICATIONS AND USAGE

Attention Deficit Disorders, Narcolepsy

Attention Deficit Disorders (previously known as Minimal Brain Dysfunction in Children). Other terms

being used to describe the behavioral syndrome below include: Hyperkinetic Child Syndrome, Minimal

Brain Damage, Minimal Cerebral Dysfunction, Minor Cerebral Dysfunction.

METADATE ER is indicated as an integral part of a total treatment program which typically includes

other remedial measures (psychological, educational, social) for a stabilizing effect in children with a

behavioral syndrome characterized by the following group of developmentally inappropriate symptoms:

moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity.

The diagnosis of this syndrome should not be made with finality when these symptoms are only of

comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal

EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not

be warranted.

Special Diagnostic Considerations

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

diagnosis requires the use not only of medical but of special psychological, educational, and social

resources.

Characteristics commonly reported include: chronic history of short attention span, distractibility,

emotional lability, impulsivity, and moderate-to-severe hyperactivity; minor neurological signs and

0→∞,

max,

0→∞

0→∞

abnormal EEG. Learning may or may not be impaired. The diagnosis must be based upon a complete

history and evaluation of the child and not solely on the presence of one or more of these

characteristics.

Drug treatment is not indicated for all children with this syndrome. Stimulants are not intended for use in

the child who exhibits symptoms secondary to environmental factors and/or primary psychiatric

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

intervention is generally necessary. When remedial measures alone are insufficient, the decision to

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

severity of the child's symptoms.

CONTRAINDICATIONS

Agitation

Marked anxiety, tension and agitation are contraindications to METADATE ER, since the drug may

aggravate these symptoms.

Hypersensitivity To Methylphenidate Or Other Excipients

METADATE ER is contraindicated in patients known to be hypersensitive to methylphenidate or other

components of the product.

METADATE ER contains lactose. Therefore, patients with rare hereditary problems of galactose

intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this

medicine.

Glaucoma

METADATE ER is contraindicated in patients with glaucoma.

Tics

METADATE ER is contraindicated in patients with motor tics or with a family history or diagnosis of

Tourette's syndrome (see ADVERSE REACTIONS).

Monoamine Oxidase Inhibitors

METADATE ER is contraindicated during treatment with monoamine oxidase inhibitors, and also within

a minimum of 14 days following discontinuation of a monoamine oxidase inhibitor (hypertensive crises

may result).

Hypertension And Other Cardiovascular Conditions

METADATE ER is contraindicated in patients with severe hypertension, angina pectoris, cardiac

arrhythmias, heart failure, recent myocardial infarction, hyperthyroidism or thyrotoxicosis (see

WARNINGS).

Halogenated Anaesthetics

There is a risk of sudden blood pressure increase during surgery. If surgery is planned, METADATE

ER should not be taken on the day of the surgery.

WARNINGS

Serious Cardiovascular Events

Sudden Death And Pre-existing 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 (see

CONTRAINDICATIONS).

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 (see

CONTRAINDICATIONS).

Hypertension And Other Cardiovascular Conditions

Stimulant medications cause a modest increase in average blood pressure (about 2-4 mmHg) and

average heart rate (about 3-6 bpm), 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 pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular

arrhythmia (see CONTRAINDICATIONS).

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.

Psychiatric Adverse Events

Pre-Existing Psychosis

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

patients with a pre-existing 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

children and adolescents without prior history of psychotic illness or mania can be caused by stimulants

at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the

stimulant, 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 children and adolescents 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.

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 non-medication treatment groups over 14 months, as well as in naturalistic

subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the

ages of 10 to 13 years), 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 a 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.

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.

Priapis m

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

methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug

initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism

has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). Patients

who develop abnormally sustained or frequent and painful erections should seek immediate medical

attention.

Peripheral Vasculopathy, Including Raynaud's Phenomenon

Stimulants, including METADATE ER, 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 postmarketing 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.

Visual Disturbance

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

Use In Children Under Six Years Of Age

METADATE ER should not be used in children under six years, since safety and efficacy in this age

group have not been established.

Drug Dependence

METADATE ER 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. Careful supervision is required during drug 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.

PRECAUTIONS

Patients with an element of agitation may react adversely; discontinue therapy if necessary.

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

not indicated in all cases of this behavioral syndrome and should be considered only in light of the

complete history and evaluation of the child. The decision to prescribe METADATE ER should

depend on the physician's assessment of the chronicity and severity of the child's symptoms and their

appropriateness for his/her age. Prescription should not depend solely on the presence of one or more

of the behavioral characteristics.

When these symptoms are associated with acute stress reactions, treatment with methylphenidate is

usually not indicated.

Drug Testing

METADATE ER contains methylphenidate which may result in a positive result during drug testing.

Information for Patients

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

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

its appropriate use. A patient Medication Guide is available for METADATE ER. The prescriber or

healthcare professional should instruct patients, their families, and their caregivers to read the

Medication Guide and should assist them in understanding its contents. Patients should be given the

opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they

may have. The complete text of the Medication Guide is reprinted at the end of this document. The

Medication Guide may also be obtained by calling 1-866-822-0068.

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

priapis m.

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon]

Instruct patients beginning treatment with METADATE ER about the risk of peripheral

vasculopathy, including Raynaud's Phenomenon, and in 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 METADATE ER.

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

Drug Interactions

METADATE ER should not be used in patients being treated (currently or within the proceeding two

weeks) with MAO Inhibitors (see CONTRAINDICATIONS, Monoamine Oxidase Inhibitors).

Because of possible effects on blood pressure, METADATE ER should be used cautiously with

pressor agents.

METADATE ER may decrease the effectiveness of drugs used to treat hypertension. METADATE ER

is metabolized primarily to ritalinic acid by de-esterification and not through oxidative pathways.

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

coumarin anticoagulants, anticonvulsants (e.g. phenobarbital, phenytoin, primidone), phenylbutazone, and

tricyclic drugs (e.g. imipramine, clomipramine, desipramine). Downward dosage adjustments of these

drugs may be required when given concomitantly with METADATE ER. It may be necessary to adjust

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

initiating or discontinuing methylphenidate.

In theory, there is a possibility that the clearance of methylphenidate might be affected by urinary pH,

either being increased with acidifying agents or decreased with alkalizing agents. This should be

considered when methylphenidate is given in combination with agents that alter urinary pH.

Halogenated Anesthetics

There is a risk of sudden blood pressure increase during surgery. If surgery is planned, METADATE

ER should not be taken the day of the surgery.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

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 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 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 60-74 mg/kg/day of methylphenidate.

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

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

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

Ovary (CHO) cells. Methylphenidate was negative in vivo in males and females in the mouse bone

marrow micronucleus assay.

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

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

approximately 80-fold and 8-fold the highest recommended dose on a mg/kg and mg/m basis,

respectively.

Pregnancy

Pregnancy Category C

In studies conducted in rats and rabbits, methylphenidate was administered orally at doses of up to 75 and

200 mg/kg/day, respectively, during the period of organogenesis. Teratogenic effects (increased

incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 40

times the maximum recommended human dose (MRHD) on a mg/m basis. The no effect level for

embryo-fetal development in rabbits was 60 mg/kg/day (11 times the MRHD on a mg/m basis). There

was no evidence of specific teratogenic activity in rats, although increased incidences of fetal skeletal

variations were seen at the highest dose level (7 times the MRHD on a mg/m basis), which was also

maternally toxic. The no effect level for embryo-fetal development in rats was 25 mg/kg/day (2 times the

MRHD on a mg/m basis). When methylphenidate was administered to rats throughout pregnancy and

lactation at doses of up to 45 mg/kg/day, offspring body weight gain was decreased at the highest dose

(4 times the MRHD on a mg/m basis), but no other effects on postnatal development were observed.

The no effect level for pre- and postnatal development in rats was 15 mg/kg/day (equal to the MRHD on

a mg/m basis).

Adequate and well-controlled studies in pregnant women have not been conducted. METADATE ER

should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 METADATE ER is administered to a nursing woman.

Pediatric Use

METADATE ER should not be used in children under six years of age (see WARNINGS).

In a study conducted in young rats, methylphenidate was administered orally at doses of up to 100

mg/kg/day for 9 weeks, starting early in the postnatal period (Postnatal Day 7) and continuing through

sexual maturity (Postnatal Week 10). When these animals were tested as adults (Postnatal Weeks 13-14),

decreased spontaneous locomotor activity was observed in males and females previously treated with

50 mg/kg/day (approximately 6 times the maximum recommended human dose [MRHD] on a mg/m

basis) or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed

to the highest dose (12 times the MRHD on a mg/m basis). The no effect level for juvenile

neurobehavioral development in rats was 5 mg/kg/day (half the MRHD on a mg/m basis). The clinical

significance of the long-term behavioral effects observed in rats is unknown.

ADVERSE REACTIONS

Nervousness and insomnia are the most common adverse reactions but are usually controlled by

reducing dosage and omitting the drug in the afternoon or evening. Other reactions include

hypersensitivity (including skin rash, pruritus, urticaria, fever, arthralgia, exfoliative dermatitis,

erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic

purpura); anorexia; nausea; dizziness; palpitations; headache; dyskinesia; drowsiness; blood pressure

and pulse changes, both up and down; tachycardia; angina; cardiac arrhythmia; abdominal pain; weight

loss during prolonged therapy; libido changes. There have been rare reports of Tourette's syndrome

and obsessive-compulsive disorder. Toxic psychosis has been reported. Although a definite causal

relationship has not been established, the following have been reported in patients taking this drug:

instances of abnormal liver function, ranging from transaminase elevation to hepatic coma; isolated

cases of cerebral arteritis and/or occlusion; leukopenia and/or anemia; transient depressed mood;

aggressive behavior; a few instances of scalp hair loss. Very rare reports of neuroleptic malignant

syndrome (NMS) have been received, and, in most of these, patients were concurrently receiving

therapies associated with NMS. In a single report, a ten year old boy who had been taking

methylphenidate for approximately 18 months experienced an NMS-like event within 45 minutes of

ingesting his first dose of venlafaxine. It is uncertain whether this case represented a drug-drug

interaction, a response to either drug alone, or some other cause.

In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and

tachycardia may occur more frequently; however, any of the other adverse reactions listed above may

also occur.

Postmarketing Experience

In addition to the adverse events listed above, the following have been reported in patients receiving

methylphenidate worldwide. The list is alphabetized: abnormal behavior, aggression, anxiety, cardiac

arrest, depression, fixed drug eruption, hyperactivity, irritability, migraine, obsessive-compulsive

disorder, peripheral coldness, Raynaud's phenomenon, reversible ischaemic neurological deficit,

sudden death, suicidal behavior (including completed suicide), and thrombocytopenia. Data are

insufficient to support an estimation of incidence or establish causation.

DOSAGE AND ADMINISTRATION

Dosage should be individualized according to the needs and responses of the patient.

Adults

Methylphenidate Hydrochloride, USP Immediate-Release Tablets

Administer in divided doses 2 or 3 times daily, preferably 30 to 45 minutes before meals. Average

dosage is 20 to 30 mg daily. Some patients may require 40 to 60 mg daily. In others, 10 to 15 mg daily

will be adequate. Patients who are unable to sleep if medication is taken late in the day should take the

last dose before 6 p.m.

Extended-Release Tablets

METADATE ER Tablets have a duration of action of approximately 8 hours. Therefore, the extended-

release tablets may be used in place of the immediate-release tablets when the 8-hour dosage of

METADATE ER Tablets corresponds to the titrated 8-hour dosage of the immediate-release tablets.

METADATE ER Tablets must be swallowed whole and never crushed or chewed.

Children (6 Years And Over)

Methylphenidate hydrochloride tablets should be initiated in small doses, with gradual weekly

increments. Daily dosage above 60 mg is not recommended.

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

should be discontinued.

Methylphenidate Hydrochloride, USP Immediate-Release Tablets

Start with 5 mg twice daily (before breakfast and lunch) with gradual increments of 5 to 10 mg weekly.

Extended-Release Tablets

METADATE ER Tablets have a duration of action of approximately 8 hours. Therefore, the extended-

release tablets may be used in place of the immediate-release tablets when the 8-hour dosage of

METADATE ER Tablets corresponds to the titrated 8-hour dosage of the immediate-release tablets.

METADATE ER Tablets must be swallowed whole and never crushed or chewed.

If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage, or, if

necessary, discontinue the drug.

METADATE ER should be periodically discontinued to assess the child's condition. Improvement may

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

Drug treatment should not and need not be indefinite and usually may be discontinued after puberty.

OVERDOSAGE

Signs and symptoms of acute overdosage, resulting principally from overstimulation of the central

nervous system and from excessive sympathomimetic effects, may include the following: vomiting,

agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria,

confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia,

palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous membranes.

Consult with a Certified Poison Control Center regarding treatment for up-to-date guidance and advice.

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. In the presence of severe intoxication, use a carefully titrated dosage of

a short-acting barbiturate before performing gastric lavage. 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 hyperpyrexia.

Efficacy of peritoneal dialysis or extracorporeal hemodialysis for methylphenidate overdosage has not

been established.

HOW SUPPLIED

METADATE ER Tablets (methylphenidate hydrochloride extended-release tablets, USP) are available

as follows:

20 mg: Round, white, uncoated, unscored, debossed "562 MD".

NDC 53014-594-07 Bottle of 100's

NOTE: METADATE ER Tablets are color-additive free.

Pharmacis t

Dispense in a tight container as defined in the USP with a child-resistant closure.

Store at 20° - 25°C (68°-77°F); excursions permitted to 15° - 30°C (59° - 86°F) [See USP Controlled

Room Temperature]. Protect from moisture.

For Medical Information

Contact: Medical Affairs Department

Phone: (866) 822-0068

Fax: (770) 970-8859

Manufactured for

UCB, Inc.

Smyrna, GA 30080

Rev. 9E 01/2014

METADATE is a registered trademark of the UCB Group of companies

© 2014, UCB, Inc., Smyrna, GA 30080 All rights reserved. Printed in U.S.A.

MEDICATION GUIDE

METADATE® ER

(methylphenidate HCl extended-release tablets, USP) Tablets CII

Read the Medication Guide that comes with METADATE ER 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 METADATE ER.

What is the most important information I should know about METADATE ER?

The following have been reported with use of methylphenidate HCl, USP 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 have 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 METADATE

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

with METADATE ER.

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 METADATE ER.

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 have any new or worsening mental symptoms or

problems while taking METADATE ER, especially seeing or hearing things that are not real,

believing things that are not real, or are suspicious.

3. Circulation Problems in fingers and toes [Peripheral vasculopathy, including Raynaud's

phenomenon]: fingers or toes may feel numb, cool, painful, and/or 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 the fingers and 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 METADATE ER.

What Is METADATE ER?

METADATE ER is a central nervous system stimulant prescription medicine. It is used for the

treatment of Attention-Deficit Hyperactivity Disorder (ADHD).

METADATE ER may help increase attention and decrease impulsiveness and hyperactivity in patients

with ADHD.

METADATE ER should be used as a part of a total treatment program for ADHD that may include

counseling or other therapies.

METADATE ER is a federally controlled substance (CII) because it can be abused or lead

to dependence. Keep METADATE ER in a safe place to prevent misuse and abuse. Selling

or giving away METADATE ER 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 METADATE ER?

METADATE ER should not be taken if you or your child:

are 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.

have severe high blood pressure or a heart problem

have hyperthyroidism

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

oxidase inhibitor or MAOI.

are allergic to anything in METADATE ER. See the end of this Medication Guide for a complete

list of ingredients.

METADATE ER should not be used in children less than 6 years old because it has not been studied in

this age group.

METADATE ER may not be right for you or your child. Before starting METADATE ER tell

your or your child's doctor about all health conditions (or a family history of) including:

heart problems, heart defects, 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 or toes

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

Can METADATE ER 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. METADATE ER 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 METADATE ER.

Your doctor will decide whether METADATE ER can be taken with other medicines.

Especially tell your doctor if you or your child takes:

anti-depression 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 METADATE ER without talking to your doctor first.

How should METADATE ER be taken?

Take METADATE ER exactly as prescribed. Your doctor may adjust the dose until it is right for

you or your child.

Take METADATE ER once a day. METADATE ER is an extended release tablet. It releases

medicine into your body throughout the day.

Do not chew or crush METADATE ER tablets. Swallow METADATE ER tablets whole with

water or other liquids. Tell your doctor if you or your child cannot swallow METADATE ER

whole. A different medicine may need to be prescribed.

From time to time, your doctor may stop METADATE ER treatment for a while to check ADHD

symptoms.

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

METADATE ER. Children should have their height and weight checked often while taking

METADATE ER. METADATE ER treatment may be stopped if a problem is found during these

check-ups.

If you or your child takes too much METADATE ER or overdoses, call your doctor or

poison control center right away, or get emergency treatment.

What are possible side effects of METADATE ER?

See "What is the most important information I should know about METADATE ER?" 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

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.

Common side effects include:

headache

decreased appetite

stomach ache

nervousness

trouble sleeping

dizziness

nausea

heart palpitations

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.

How should I store METADATE ER?

Store METADATE ER in a safe place at room temperature, 59 to 86° F (15 to 30° C). Protect from

moisture.

Keep METADATE ER and all medicines out of the reach of children.

General information about METADATE ER

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

use METADATE ER for a condition for which it was not prescribed. Do not give METADATE ER 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 METADATE ER. If you

would like more information, talk with your doctor. You can ask your doctor or pharmacist for

information about METADATE ER that was written for healthcare professionals. For more information

about METADATE ER call 1-866-822-0068.

What are the ingredients in METADATE ER?

Active Ingredient: methylphenidate HCl

Inactive Ingredients: cetyl alcohol, ethylcellulose, anhydrous lactose and magnesium stearate.

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

Manufactured for

UCB, Inc.

Smyrna, GA 30080

METADATE is a registered trademark of the UCB Group of companies

©2014, UCB, Inc., Smyrna, GA 30080

All rights reserved. Printed in U.S.A.

3E 01/2014

PRINCIPAL DISPLAY PANEL - 20 mg Tablet Bottle Label

NDC 53014-594-07

Metadate

ER Tablets

(methylphenidate

hydrochloride extended-

release tablets, USP)

CII

100 Tablets

20 mg

UCB, Inc.

A Medication Guide is required

for every prescription dispensed.

Please use accompanying

Medication Guide.

Rx Only

METADATE ER

methylphenidate hydrochloride tablet, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:530 14-59 4

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

methylphenida te hydro chlo ride (UNII: 4B3SC438 HI) (methylphenidate -

UNII:20 7ZZ9 QZ49 )

me thylphe nida te

hydro c hlo ride

20 mg

®

Unither Manufacturing, LLC

Inactive Ingredients

Ingredient Name

Stre ng th

cetyl a lco ho l (UNII: 9 36 JST6 JCN)

ethylcellulo ses (UNII: 7Z8 S9 VYZ4B)

a nhydro us la cto se (UNII: 3SY5LH9 PMK)

ma g nesium stea ra te (UNII: 70 0 9 7M6 I30 )

Product Characteristics

Color

WHITE (White)

S core

no sco re

S hap e

ROUND (Ro und)

S iz e

8 mm

Flavor

Imprint Code

56 2;MD

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:530 14-59 4-0 7

10 0 in 1 BOTTLE

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 8 9 6 0 1

0 6 /0 1/19 8 8

Labeler -

Unither Manufacturing, LLC (079176615)

Revised: 1/2014

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