BUPROPION HYDROCHLORIDE XL- bupropion hydrochloride tablet, extended release

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

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Active ingredient:
BUPROPION HYDROCHLORIDE (UNII: ZG7E5POY8O) (BUPROPION - UNII:01ZG3TPX31)
Available from:
Zhejiang Jutai Pharamceutical Co., Ltd
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Bupropion hydrochloride extended-release tablets (XL) are indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM). The efficacy of the immediate-release formulation of bupropion was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult patients with MDD. The efficacy of the sustained-release formulation of bupropion in the maintenance treatment of MDD was established in a long-term (up to 44 weeks), placebo-controlled trial in patients who had responded to bupropion in an 8-week study of acute treatment [see Clinical Studies (14.1)]. Bupropion hydrochloride extended-release tablets (XL) are indicated for the prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD). The efficacy of bupropion hydrochloride extended-release tablets in the prevention of seasonal major depressive episodes was established in 3 placebo-controll
Product summary:
Bupropion hydrochloride extended-release tablets (XL), 300 mg of bupropion hydrochloride, are white to off-white, round tablets printed with "T011". They are supplied as follows: Bottles of 30 tablets NDC 71765-002-03 Bottles of  90 tablets NDC 71765-002-09  Bottles of 500 tablets NDC 71765-002-50. Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light.   Bupropion hydrochloride extended-release tablets (XL) may have an odor.
Authorization status:
Abbreviated New Drug Application
Authorization number:
71765-002-03, 71765-002-09, 71765-002-50

BUPROPION HYDROCHLORIDE XL- bupropion hydrochloride tablet, extended release

Zhejiang Jutai Pharamceutical Co., Ltd

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MEDICATION GUIDE

Bupropion Hydrochloride (bue proe' pee on hye'' droe klor' ide) Extended-Release Tablets (XL)

IMPORTANT: Be sure to read the three sections of this Medication Guide. The first section is about the risk

of suicidal thoughts and actions with antidepressant medicines; the second section is about the risk of

changes in thinking and behavior, depression and suicidal thoughts or actions with medicines used to quit

smoking; and the third section is entitled “What Other Important Information Should I Know About

Bupropion Hydrochloride Extended-Release Tablets (XL)?”

Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions

This section of the Medication Guide is only about the risk of suicidal thoughts and actions with

antidepressant medicines.

What is the most important information I should know about antidepressant medicines, depression and other

serious mental illnesses, and suicidal thoughts or actions?

Antidepressant medicines may increase the risk of suicidal thoughts or actions in some children,

teenagers, or young adults within the first few months of treatment.

Depression or other serious mental illnesses are the most important causes of suicidal thoughts and

actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These

include people who have (or have a family history of) bipolar illness (also called manic-depressive

illness) or suicidal thoughts or actions.

How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?

Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts,

or feelings. This is very important when an antidepressant medicine is started or when the dose

is changed.

Call your healthcare provider right away to report new or sudden changes in mood, behavior,

thoughts, or feelings.

Keep all follow up visits with your healthcare provider as scheduled. Call the healthcare

provider between visits as needed, especially if you have concerns about symptoms.

Call your healthcare provider right away if you or your family member has any of the following symptoms,

especially if they are new, worse, or worry you:

thoughts about suicide or dying

attempts to commit suicide

new or worse depression

new or worse anxiety

feeling very agitated or restless

panic attacks

trouble sleeping (insomnia)

new or worse irritability

acting aggressive, being angry, or violent

acting on dangerous impulses

an extreme increase in activity and talking (mania)

other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an

antidepressant medicine suddenly can cause other symptoms.

Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss

all the risks of treating depression and also the risks of not treating it. Patients and their families or

other caregivers should discuss all treatment choices with the healthcare provider, not just the use of

antidepressants.

Antidepressant medicines have other side effects. Talk to the healthcare provider about the side

effects of the medicine prescribed for you or your family member.

Antidepressant medicines can interact with other medicines. Know all of the medicines that you or

your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start

new medicines without first checking with your healthcare provider.

It is not known if bupropion hydrochloride extended-release tablets (XL) are safe and effective in children

under the age of 18.

Quitting Smoking, Quit-Smoking Medications, Changes in Thinking and Behavior, Depression, and Suicidal

Thoughts or Actions

This section of the Medication Guide is only about the risk of changes in thinking and behavior, depression

and suicidal thoughts or actions with drugs used to quit smoking. Although bupropion hydrochloride

extended-release tablets (XL) are not a treatment for quitting smoking, they contain the same active

ingredient (bupropion hydrochloride) as ZYBAN ® which is used to help patients quit smoking.

Talk to your healthcare provider or your family member’s healthcare provider about:

all risks and benefits of quit-smoking medicines.

all treatment choices for quitting smoking.

When you try to quit smoking, with or without bupropion you may have symptoms that may be due to

nicotine withdrawal, including:

urge to smoke

depressed mood

trouble sleeping

irritability

frustration

anger

feeling anxious

difficulty concentrating

restlessness

decreased heart rate

increased appetite

weight gain

Some people have even experienced suicidal thoughts when trying to quit smoking without medication.

Sometimes quitting smoking can lead to worsening of mental health problems that you already have, such as

depression.

Some people have had serious side effects while taking bupropion to help them quit smoking, including:

New or worse mental health problems , such as changes in behavior or thinking, aggression, hostility,

agitation, depression, or suicidal thoughts or actions. Some people had these symptoms when they began

taking bupropion, and others developed them after several weeks of treatment, or after stopping bupropion.

These symptoms happened more often in people who had a history of mental health problems before taking

bupropion than in people without a history of mental health problems.

Stop taking bupropion hydrochloride extended-release tablets (XL) and call your healthcare provider right

away if you, your family, or caregiver notice any of these symptoms. Work with your healthcare provider to

decide whether you should continue to take bupropion hydrochloride extended-release tablets (XL). In many

people, these symptoms went away after stopping bupropion hydrochloride extended-release tablets (XL),

but in some people symptoms continued after stopping bupropion hydrochloride extended-release tablets

(XL). It is important for you to follow-up with your healthcare provider until your symptoms go away.

Before taking bupropion hydrochloride extended-release tablets (XL) , tell your healthcare provider if you

have ever had depression or other mental health problems. You should also tell your healthcare provider

about any symptoms you had during other times you tried to quit smoking, with or without bupropion.

What Other Important Information Should I Know About Bupropion Hydrochloride Extended-Release

Tablets (XL)?

Seizures: There is a chance of having a seizure (convulsion, fit) with bupropion hydrochloride

extended-release tablets (XL), especially in people:

with certain medical problems.

who take certain medicines.

The chance of having seizures increases with higher doses of bupropion hydrochloride extended-release

tablets (XL). For more information, see the sections “Who should not take bupropion hydrochloride

extended-release tablets (XL)?” and “What should I tell my healthcare provider before taking bupropion

hydrochloride extended-release tablets (XL)?” Tell your healthcare provider about all of your medical

conditions and all the medicines you take. Do not take any other medicines while you are taking bupropion

hydrochloride extended-release tablets (XL) unless your healthcare provider has said it is okay to take them.

If you have a seizure while taking bupropion hydrochloride extended-release tablets (XL), stop taking the

tablets and call your healthcare provider right away. Do not take bupropion hydrochloride extended-release

tablets (XL) again if you have a seizure.

High blood pressure (hypertension). Some people get high blood pressure that can be severe, while

taking bupropion hydrochloride extended-release tablets (XL). The chance of high blood pressure

may be higher if you also use nicotine replacement therapy (such as a nicotine patch) to help you stop

smoking (see the section of this Medication Guide called “How should I take bupropion

hydrochloride extended-release tablets (XL)?”).

Manic episodes. Some people may have periods of mania while taking bupropion hydrochloride

extended-release tablets (XL) including:

Greatly increased energy

Severe trouble sleeping

Racing thoughts

Reckless behavior

Unusually grand ideas

Excessive happiness or irritability

Talking more or faster than usual

If you have any of the above symptoms of mania, call your healthcare provider.

Unusual thoughts or behaviors. Some patients have unusual thoughts or behaviors while taking

bupropion hydrochloride extended-release tablets (XL), including delusions (believe you are someone

else), hallucinations (seeing or hearing things that are not there), paranoia (feeling that people are

against you), or feeling confused. If this happens to you, call your healthcare provider.

Visual problems.

eye pain

changes in vision

swelling or redness in or around the eye.

Only some people are at risk for these problems. You may want to undergo an eye examination to see if you

are at risk and receive preventative treatment if you are.

Severe allergic reactions. Some people can have severe allergic reactions to bupropion hydrochloride

extended-release tablets (XL). Stop taking bupropion hydrochloride extended-release tablets (XL) and

call your healthcare provider right away if you get a rash, itching, hives, fever, swollen lymph glands,

painful sores in the mouth or around the eyes, swelling of the lips or tongue, chest pain, or have

trouble breathing. These could be signs of a serious allergic reaction.

What are bupropion hydrochloride extended-release tablets (XL)?

Bupropion hydrochloride extended-release tablets (XL) should be used with a patient support program. It is

important to participate in the behavioral program, counseling, or other support program your healthcare

professional recommends.

Quitting smoking can lower your chances of having lung disease, heart disease, or getting certain types of

cancer that are related to smoking.

Who should not take bupropion hydrochloride extended-release tablets (XL)?

Do not take bupropion hydrochloride extended-release tablets (XL) if you:

have or had a seizure disorder or epilepsy.

have or had an eating disorder such as anorexia nervosa or bulimia.

are taking any other medicines that contain bupropion, including WELLBUTRIN ® , WELLBUTRIN

® SR, APLENZIN ® , ZYBAN ® , or FORFIVO XL ® . Bupropion is the same active ingredient that

is in bupropion hydrochloride extended-release tablets (XL).

drink a lot of alcohol and abruptly stop drinking, take medicines called sedatives (these make you

sleepy) or benzodiazepines, or anti-seizure medicines, and you stop taking them all of a sudden.

take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are

not sure if you take an MAOI, including the antibiotic linezolid.

do not take an MAOI within 2 weeks of stopping bupropion hydrochloride extended-release

tablets (XL) unless directed to do so by your healthcare provider.

do not start bupropion hydrochloride extended-release tablets (XL) if you stopped taking an

MAOI in the last 2 weeks unless directed to do so by your healthcare provider.

are allergic to the active ingredient in bupropion hydrochloride extended-release tablets (XL),

bupropion, or to any of the inactive ingredients. See the end of this Medication Guide for a complete

list of ingredients in bupropion hydrochloride extended-release tablets (XL).

What should I tell my healthcare provider before taking bupropion hydrochloride extended-release tablets

(XL) ?

Tell your healthcare provider if you have ever had depression, suicidal thoughts or actions, or other mental

health problems. You should also tell your healthcare provider about any symptoms you had during other

times you tried to quit smoking, with or without bupropion hydrochloride extended-release tablets (XL). See

“Quitting Smoking, Quit-Smoking Medications, Changes in Thinking and Behavior, Depression, and

Suicidal Thoughts or Actions.”

Tell your healthcare provider about your other medical conditions, including if you:

have liver problems, especially cirrhosis of the liver.

have kidney problems.

have, or have had, an eating disorder such as anorexia nervosa or bulimia.

have had a head injury.

have had a seizure (convulsion, fit).

have a tumor in your nervous system (brain or spine).

have had a heart attack, heart problems, or high blood pressure.

are a diabetic taking insulin or other medicines to control your blood sugar.

drink alcohol.

abuse prescription medicines or street drugs.

are pregnant or plan to become pregnant.

are breastfeeding. Bupropion hydrochloride passes into your milk in small amounts.

Tell your healthcare provider about all the medicines you take , including prescription, over-the-counter

medicines, vitamins, and herbal supplements. Many medicines increase your chances of having seizures or

other serious side effects if you take them while you are taking bupropion hydrochloride extended-release

tablets (XL).

How should I take bupropion hydrochloride extended-release tablets (XL)?

Start bupropion hydrochloride extended-release tablets (XL) before you stop smoking to give

bupropion hydrochloride extended-release tablets (XL) time to build up in your body. It takes about 1

week for bupropion hydrochloride extended-release tablets (XL) to start working.

Pick a date to stop smoking that is during the second week you are taking bupropion hydrochloride

extended-release tablets (XL).

Take bupropion hydrochloride extended-release tablets (XL) exactly as prescribed by your healthcare

provider. Do not change your dose or stop taking bupropion hydrochloride extended-release tablets

(XL) without talking with your healthcare provider first.

Bupropion hydrochloride extended-release tablets (XL) are usually taken for 7 to 12 weeks. Your

healthcare provider may decide to prescribe bupropion hydrochloride extended-release tablets (XL)

for longer than 12 weeks to help you stop smoking. Follow your healthcare provider’s instructions.

Swallow bupropion hydrochloride extended-release tablets (XL) whole. Do not chew, cut, or crush

bupropion hydrochloride extended-release tablets (XL). If you do, the medicine will be released into

your body too quickly. If this happens you may be more likely to get side effects including seizures.

Tell your healthcare provider if you cannot swallow tablets.

Bupropion hydrochloride extended-release tablets (XL) may have an odor. This is normal.

Take your doses of bupropion hydrochloride extended-release tablets (XL) at least 8 hours apart.

You may take bupropion hydrochloride extended-release tablets (XL) with or without food.

It is not dangerous to smoke and take bupropion hydrochloride extended-release tablets (XL) at the

same time. But, you will lower your chance of breaking your smoking habit if you smoke after the

date you set to stop smoking.

You may use bupropion hydrochloride extended-release tablets (XL) and nicotine patches (a type of

nicotine replacement therapy) at the same time, following the precautions below.

You should only use bupropion hydrochloride extended-release tablets (XL) and nicotine

patches together under the care of your healthcare provider. Using bupropion hydrochloride

extended-release tablets (XL) and nicotine patches together may raise your blood pressure, and

sometimes this can be severe.

Tell your healthcare provider if you plan to use nicotine patches. Your healthcare provider

should check your blood pressure regularly if you use nicotine patches with bupropion

hydrochloride extended-release tablets (XL) to help you quit smoking.

If you miss a dose, do not take an extra dose to make up for the dose you missed. Wait and take your

next dose at the regular time. This is very important. Too much bupropion hydrochloride extended-

release tablets (XL) can increase your chance of having a seizure.

If you take too much bupropion hydrochloride extended-release tablets (XL), or overdose, call your

local emergency room or poison control center right away.

Do not take any other medicines while taking bupropion hydrochloride extended-release tablets (XL) unless

your healthcare provider has told you it is okay.

What should I avoid while taking bupropion hydrochloride extended-release tablets (XL)?

Limit or avoid using alcohol during treatment with bupropion hydrochloride extended-release tablets

(XL). If you usually drink a lot of alcohol, talk with your healthcare provider before suddenly

stopping. If you suddenly stop drinking alcohol, you may increase your chance of having seizures.

Do not drive a car or use heavy machinery until you know how bupropion hydrochloride extended-

release tablets (XL) affects you. bupropion hydrochloride extended-release tablets (XL) can affect

your ability to do these things safely.

What are possible side effects of bupropion hydrochloride extended-release tablets (XL)?

Bupropion hydrochloride extended-release tablets (XL) can cause serious side effects. See the sections at the

beginning of this Medication Guide for information about serious side effects of bupropion hydrochloride

extended-release tablets (XL).

The most common side effects of bupropion hydrochloride extended-release tablets (XL) include:

trouble sleeping

feeling anxious

stuffy nose

nausea

dry mouth

constipation

dizziness

joint aches

If you have trouble sleeping, do not take bupropion hydrochloride extended-release tablets (XL) too close to

bedtime.

Tell your healthcare provider right away about any side effects that bother you.

These are not all the possible side effects of bupropion hydrochloride extended-release tablets (XL). For

more information, ask your healthcare provider or pharmacist.

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 Tulex Pharmaceuticals Inc. at 1-609-619-3098.

How should I store bupropion hydrochloride extended-release tablets (XL)?

Store bupropion hydrochloride extended-release tablets at room temperature between 59° and 86°F

(15° to 30°C). Protect from light.

Keep bupropion hydrochloride extended-release tablets (XL) and all medicines out of the reach of children.

General information about the safe and effective use of bupropion hydrochloride extended-release tablets

(XL).

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

bupropion hydrochloride extended-release tablets (XL) for a condition for which it was not prescribed. Do

not give bupropion hydrochloride extended-release tablets (XL) to other people, even if they have the same

symptoms you have. It may harm them.

If you take a urine drug screening test, bupropion hydrochloride extended-release tablets (XL) may make the

test result positive for amphetamines. If you tell the person giving you the drug screening test that you are

taking bupropion hydrochloride extended-release tablets (XL), they can do a more specific drug screening

test that should not have this problem.

This Medication Guide summarizes important information about bupropion hydrochloride extended-release

tablets (XL). If you would like more information, talk with your healthcare provider. You can ask your

healthcare provider or pharmacist for information about bupropion hydrochloride extended-release tablets

(XL) that is written for health professionals.

For more information about bupropion hydrochloride extended-release tablets (XL), call Tulex

Pharmaceuticals Inc. at 1 609-619-3098.

What are the ingredients in bupropion hydrochloride extended-release tablets (XL)?

Active ingredient: bupropion hydrochloride.

Inactive ingredients:alcohol, ethylcellulose, hydrochloric acid, hydroxypropyl cellulose, hypromellose,

methacrylic acid and ethyl acrylate copolymer, polyethylene glycol, povidone, purified water, silicon

dioxide, stearic acid and talc. The tablets are printed with edible black ink, which contains ferrosoferric

oxide, hypromellose, propylene glycol, and purified water.

Manufactured by:

Tulex Pharmaceuticals Inc.

Cranbury, NJ 08512 USA

Manufactured for:

Zhejiang Jutai Pharmaceuticals Co., Ltd.

No. 51 Donggang Road, Keecheng District,

Quzhou City, Zhejiang Province, China 324022

All product/brand names are the trademarks of their respective owners.

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

PI0010000203 Rev: 08/2019

Revised: 9/2019

Document Id: 92c0bab1-f2d4-2171-e053-2995a90ac526

34391-3

Set id: 1f25201c-1a15-4da1-a250-e91040df8774

Version: 8

Effective Time: 20190917

Zhejiang Jutai Pharamceutical Co., Ltd

BUPROPION HYDROCHLORIDE XL- bupropion hydrochloride tablet, extended release

Zhejiang Jutai Pharamceutical Co., Ltd

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use BUPROPION HYDROCHLORIDE

EXTENDED-RELEASE TABLETS (XL) safely and effectively. See full prescribing information for BUPROPION

HYDROCHLORIDE EXTENDED-RELEASE TABLETS (XL).

BUPROPION HYDROCHLORIDE extended-release tablets (XL), for oral use

Initial U.S. Approval: 1985

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

See full prescribing information for complete boxed warning.

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking

antidepressants.

Monitor for worsening and emergence of suicidal thoughts and behaviors. ( 5.1)

RECENT MAJOR CHANGES

Boxed Warning 05/2017

Warnings and Precautions, Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation

Treatment ( 5.2) 05/2017

INDICATIONS AND USAGE

Bupropion hydrochloride extended-release tablets (XL) are an aminoketone antidepressant, indicated for the treatment of

major depressive disorder (MDD) and prevention of seasonal affective disorder (SAD). Periodically reevaluate long-term

usefulness for the individual patient. ( 1)

DOSAGE AND ADMINISTRATION

Ge ne ral:

Increase dose gradually to reduce seizure risk. ( 2.1, 5.3)

Periodically reassess the dose and need for maintenance treatment. ( 2.2)

Major Depressive Disorder

Starting dose: 150 mg once daily. Usual target dose: 300 mg once daily ( 2.2)

After 4 days, may increase the dose to 300 mg once daily. ( 2.2)

Seasonal Affective Disorder

Initiate treatment in the autumn prior to onset of seasonal depressive symptoms. ( 2.3)

Starting dose: 150 mg once daily. Usual target dose: 300 mg once daily. ( 2.3)

After one week, may increase the dose to 300 mg once daily. ( 2.3)

Continue treatment through the winter season. ( 2.3)

Hepatic Impairment

Moderate to severe hepatic impairment: 150 mg every other day ( 2.6)

Mild hepatic impairment: Consider reducing the dose and/or frequency of dosing. ( 2.6, 8.7)

Renal Impairment

Consider reducing the dose and/or frequency of dosing. ( 2.7, 8.6)

DOSAGE FORMS AND STRENGTHS

Extended-release tablets: 300 mg ( 3)

CONTRAINDICATIONS

Seizure disorder. ( 4, 5.3)

Current or prior diagnosis of bulimia or anorexia nervosa ( 4, 5.3)

Current or prior diagnosis of bulimia or anorexia nervosa ( 4, 5.3)

Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, antiepileptic drugs. ( 4, 5.3)

Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with bupropion

hydrochloride extended-release tablets (XL) or within 14 days of stopping treatment with bupropion hydrochloride

extended-release tablets (XL). Do not use bupropion hydrochloride extended-release tablets (XL) within 14 days of

stopping an MAOI intended to treat psychiatric disorders. In addition, do not start bupropion hydrochloride extended-

release tablets (XL) in a patient who is being treated with linezolid or intravenous methylene blue. ( 4, 7.6)

Known hypersensitivity to bupropion or other ingredients of bupropion hydrochloride extended-release tablets (XL) (

4, 5.8)

WARNINGS AND PRECAUTIONS

Neuropsychiatric Adverse Events During Smoking Cessation: Postmarketing reports of serious or clinically significant

neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis,

hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as

suicidal ideation, suicide attempt, and completed suicide. Observe patients attempting to quit smoking with bupropion

hydrochloride extended-release tablets (XL) for the occurrence of such symptoms and instruct them to discontinue

bupropion hydrochloride extended-release (XL) tablets and contact a healthcare provider if they experience such

adverse events. ( 5.2)

Seizure Risk: The risk is dose-related. Can minimize risk by limiting daily dose to 450 mg and gradually increasing the

dose. Discontinue if seizure occurs. ( 4, 5.3, 7.3)

Hypertension: Bupropion hydrochloride extended-release tablets (XL) can increase blood pressure. Monitor blood

pressure before initiating treatment and periodically during treatment. ( 5.4)

Activation of Mania/Hypomania: Screen patients for bipolar disorder and monitor for these symptoms. ( 5.5)

Psychosis and Other Neuropsychiatric Reactions: Instruct patients to contact a healthcare professional if such reactions

occur. ( 5.6)

Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles

treated with antidepressants. ( 5.7)

ADVERSE REACTIONS

Most common adverse reactions are (incidence ≥5%; ≥2× placebo rate): dry mouth, nausea, insomnia, dizziness,

pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency,

rash. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Tulex Pharmaceuticals Inc at 1-609-619-3098 or FDA

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

DRUG INTERACTIONS

CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir,

efavirenz, carbamazepine, phenobarbital, and phenytoin) based on clinical exposure, but should not exceed the

maximum recommended dose. ( 7.1)

Drugs metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g.,

venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol,

risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide).

Consider dose reduction when using with bupropion. ( 7.2)

Drugs that lower seizure threshold: Dose bupropion hydrochloride extended-release tablets (XL) with caution. ( 5.3,

7.3)

Dopaminergic Drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly with bupropion

hydrochloride extended-release tablets (XL). ( 7.4)

MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly with bupropion hydrochloride

extended-release tablets (XL). ( 7.6)

Drug-laboratory test interactions: Bupropion hydrochloride extended-release tablets (XL) can cause false-positive urine

test results for amphetamines. ( 7.7)

USE IN SPECIFIC POPULATIONS

Pregnancy: Use only if benefit outweighs potential risk to the fetus. ( 8.1)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 8/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Major Depressive Disorder

1.2 Seasonal Affective Disorder

2 DOSAGE AND ADMINISTRATION

2.1 General Instructions for Use

2.2 Dosage for Major Depressive Disorder (MDD)

2.3 Dosage for Seasonal Affective Disorder (SAD)

2.4 Switching Patients from WELLBUTRIN® Tablets (bupropion hydrochloride tablets) or

from WELLBUTRIN® SR (bupropion hydrochloride extended-release tablets (SR))

2.5 To Discontinue Bupropion Hydrochloride Extended-Release Tablets (XL), Taper the

Dos e

2.6 Dosage Adjustment in Patients with Hepatic Impairment

2.7 Dose Adjustment in Patients with Renal Impairment

2.8 Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Antidepressant

2.9 Use of Bupropion Hydrochloride Extended-Release Tablets (XL) with Reversible MAOIs

such as Linezolid or Methylene Blue

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults

5.2 Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation Treatment

5.3 Seizure

5.4 Hypertension

5.5 Activation of Mania/Hypomania

5.6 Psychosis and Other Neuropsychiatric Reactions

5.7 Angle-Closure Glaucoma

5.8 Hypersensitivity Reactions

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Potential for Other Drugs to Affect Bupropion Hydrochloride Extended-Release Tablets

(XL)

7.2 Potential for Bupropion Hydrochloride Extended-Release Tablets (XL) to Affect Other

Drugs

7.3 Drugs That Lower Seizure Threshold

7.4 Dopaminergic Drugs (Levodopa and Amantadine)

7.5 Use with Alcohol

7.6 MAO Inhibitors

7.7 Drug-Laboratory Test Interactions

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

9.2 Abuse

10 OVERDOSAGE

10.1 Human Overdose Experience

10.2 Overdosage Management

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Major Depressive Disorder

14.2 Seasonal Affective Disorder

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

SUICIDALITY AND ANTIDEPRESSANT DRUGS

Antidepressants increased the risk of suicidal thoughts and behavior in children,

adolescents, and young adults in short-term trials. These trials did not show an increase in

the risk of suicidal thoughts and behavior with antidepressant use in subjects aged 65 and

older [see Warnings and Precautions (5.1)].

In patients of all ages who are started on antidepressant therapy, monitor closely for

worsening, and for emergence of suicidal thoughts and behaviors. Advise families and

caregivers of the need for close observation and communication with the prescriber [see

Warnings and Precautions (5.1)].

1 INDICATIONS AND USAGE

1.1 Major Depressive Disorder

Bupropion hydrochloride extended-release tablets (XL) are indicated for the treatment of major

depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM).

The efficacy of the immediate-release formulation of bupropion was established in two 4-week

controlled inpatient trials and one 6-week controlled outpatient trial of adult patients with MDD. The

efficacy of the sustained-release formulation of bupropion in the maintenance treatment of MDD was

established in a long-term (up to 44 weeks), placebo-controlled trial in patients who had responded to

bupropion in an 8-week study of acute treatment [see Clinical Studies (14.1)].

1.2 Seasonal Affective Disorder

Bupropion hydrochloride extended-release tablets (XL) are indicated for the prevention of seasonal

major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD).

The efficacy of bupropion hydrochloride extended-release tablets in the prevention of seasonal major

depressive episodes was established in 3 placebo-controlled trials in adult outpatients with a history of

MDD with an autumn-winter seasonal pattern as defined in the DSM [see Clinical Studies (14.2)].

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

2 DOSAGE AND ADMINISTRATION

2.1 General Instructions for Use

To minimize the risk of seizure, increase the dose gradually [see Warnings and Precautions (5.3)].

Bupropion hydrochloride extended-release tablets (XL) should be swallowed whole and not crushed,

divided, or chewed.

Bupropion hydrochloride extended-release tablets (XL) should be administered in the morning and may

be taken with or without food.

2.2 Dosage for Major Depressive Disorder (MDD)

The recommended starting dose for MDD is 150 mg once daily in the morning. After 4 days of dosing,

the dose may be increased to the target dose of 300 mg once daily in the morning.

It is generally agreed that acute episodes of depression require several months or longer of

antidepressant treatment beyond the response in the acute episode. It is unknown whether the bupropion

hydrochloride extended-release tablets (XL) dose needed for maintenance treatment is identical to the

dose that provided an initial response. Periodically reassess the need for maintenance treatment and the

appropriate dose for such treatment.

2.3 Dosage for Seasonal Affective Disorder (SAD)

The recommended starting dose for SAD is 150 mg once daily. After 7 days of dosing, the dose may be

increased to the target dose of 300 mg once daily in the morning. Doses above 300 mg of bupropion

HCl extended-release were not assessed in the SAD trials.

For the prevention of seasonal MDD episodes associated with SAD, initiate bupropion hydrochloride

extended-release tablets (XL) in the autumn, prior to the onset of depressive symptoms. Continue

treatment through the winter season. Taper and discontinue bupropion hydrochloride extended-release

tablets (XL) in early spring. For patients treated with 300 mg per day, decrease the dose to 150 mg once

daily before discontinuing bupropion hydrochloride extended-release tablets (XL). Individualize the

timing of initiation, and duration of treatment should be individualized, based on the patient’s historical

pattern of seasonal MDD episodes.

2.4 Switching Patients from WELLBUTRIN® Tablets (bupropion hydrochloride tablets) or from

WELLBUTRIN® SR (bupropion hydrochloride extended-release tablets (SR))

When switching patients from WELLBUTRIN

Tablets (bupropion hydrochloride tablets) to

bupropion hydrochloride extended-release tablets (XL) or from WELLBUTRIN

SR (bupropion

hydrochloride extended-release tablets (SR)) to bupropion hydrochloride extended-release tablets

(XL), give the same total daily dose when possible.

2.5 To Discontinue Bupropion Hydrochloride Extended-Release Tablets (XL), Taper the Dose

When discontinuing treatment in patients treated with bupropion hydrochloride extended-release

tablets (XL) 300 mg once daily, decrease the dose to 150 mg once daily prior to discontinuation.

2.6 Dosage Adjustment in Patients with Hepatic Impairment

In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose is

150 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider

reducing the dose and/or frequency of dosing [see Use in Specific Populations (8.7) and Clinical

Pharmacology (12.3)].

2.7 Dose Adjustment in Patients with Renal Impairment

Consider reducing the dose and/or frequency of bupropion hydrochloride extended-release tablets in

patients with renal impairment (glomerular filtration rate less than 90 mL/min) [see Use in Specific

Populations (8.6) and Clinical Pharmacology (12.3)] .

2.8 Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Antidepressant

At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and

initiation of therapy with bupropion hydrochloride extended-release tablets (XL). Conversely, at least

14 days should be allowed after stopping bupropion hydrochloride extended-release tablets

(XL) before starting an MAOI antidepressant [see Contraindications (4) and Drug Interactions (7.6)].

2.9 Use of Bupropion Hydrochloride Extended-Release Tablets (XL) with Reversible MAOIs

such as Linezolid or Methylene Blue

Do not start bupropion hydrochloride extended-release tablets (XL) in a patient who is being treated

with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase

risk of hypertensive reactions. In a patient who requires more urgent treatment of a psychiatric

condition, non-pharmacological interventions, including hospitalization, should be considered [see

Contraindications (4)].

In some cases, a patient already receiving therapy with bupropion hydrochloride extended-release

tablets (XL) may require urgent treatment with linezolid or intravenous methylene blue. If acceptable

alternatives to linezolid or intravenous methylene blue treatment are not available and the potential

benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of

hypertensive reactions in a particular patient, bupropion hydrochloride extended-release tablets (XL)

should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The

patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous

methylene blue, whichever comes first. Therapy with bupropion hydrochloride extended-release

tablets (XL) may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local

injection) or in intravenous doses much lower than 1 mg per kg with bupropion hydrochloride extended-

release tablets (XL) are unclear. The clinician should, nevertheless, be aware of the possibility of a

drug interaction with such use [see Contraindications (4)and Drug Interactions (7.6)].

3 DOSAGE FORMS AND STRENGTHS

Bupropion hydrochloride extended-release tablets (XL), 300 mg of bupropion hydrochloride, are white

to off white round tablets printed with “T011” on one side and blank on the other side.

4 CONTRAINDICATIONS

Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients with seizure

disorder.

Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients with a current

or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in

such patients treated with bupropion hydrochloride extended-release tablets (XL) [see Warnings and

Precautions (5.3)].

Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients undergoing

abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see

Warnings and Precautions (5.3)and Drug Interactions (7.3)].

The use of MAOIs (intended to treat psychiatric disorders) concomitantly with bupropion

hydrochloride extended-release tablets (XL) or within 14 days of discontinuing treatment with

bupropion hydrochloride extended-release tablets (XL) is contraindicated. There is an increased

risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (XL) are

used concomitantly with MAOIs. The use of bupropion hydrochloride extended-release

tablets (XL) within 14 days of discontinuing treatment with an MAOI is also contraindicated. Starting

bupropion hydrochloride extended-release tablets (XL) in a patient treated with reversible MAOIs

such as linezolid or intravenous methylene blue is contraindicated [see Dosage and Administration

(2.9), Warnings and Precautions (5.4) and Drug Interactions (7.6)].

Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients with known

hypersensitivity to bupropion or other ingredients of bupropion hydrochloride extended-release

tablets (XL). Anaphylactoid/anaphylactic reactions and Stevens-Johnson Syndrome have been

reported [see Warnings and Precautions (5.8)].

5 WARNINGS AND PRECAUTIONS

5.1 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of

their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes

in behavior, whether or not they are taking antidepressant medications, and this risk may persist until

significant remission occurs. Suicide is a known risk of depression and certain other psychiatric

disorders, and these disorders themselves are the strongest predictors of suicide. There has been a

long-standing concern that antidepressants may have a role in inducing worsening of depression and the

emergence of suicidality in certain patients during the early phases of treatment.

Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (Selective Serotonin

Reuptake Inhibitors [SSRIs] and others) show that these drugs increase the risk of suicidal thinking and

behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive

disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk

of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction

with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive

compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9

antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults

with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2

months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of

suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs

studied. There were differences in absolute risk of suicidality across the different indications, with the

highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable

within age strata and across indications. These risk differences (drug-placebo difference in the number

of cases of suicidality per 1000 patients treated) are provided in Table 1.

Table 1: Risk Differences in the Number of Suicidality Cases by Age Group in the Pooled

Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients

Age Range

Drug-Placebo Difference in Number of Cases

of Suicidality per 1000 Patients Treated

Increases Compared to Placebo

<18 years

14 additional cases

18-24 years

5 additional cases

Decreases Compared to Placebo

25-64 years

1 fewer case

≥65 years

6 fewer cases

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the

number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months.

However, there is substantial evidence from placebo-controlled maintenance trials in adults with

depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored

appropriately and observed closely for clinical worsening, suicidality, and unusual changes in

behavior, especially during the initial few months of a course of drug therapy, or at times of dose

changes, either increases or decreases [see Boxed Warning and Use in Specific Populations (8.4)].

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility,

aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been

reported in adult and pediatric patients being treated with antidepressants for major depressive disorder

as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the

emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal

impulses has not been established, there is concern that such symptoms may represent precursors to

emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing

the medication, in patients whose depression is persistently worse, or who are experiencing emergent

suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if

these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.

Families and caregivers of patients being treated with antidepressants for major depressive

disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the

need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior,

and the other symptoms described above, as well as the emergence of suicidality, and to report

such symptoms immediately to healthcare providers. Such monitoring should include daily

observation by families and caregivers. Prescriptions for bupropion hydrochloride extended-

release tablets (XL) should be written for the smallest quantity of tablets consistent with good

patient management, in order to reduce the risk of overdose.

5.2 Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation Treatment

Bupropion hydrochloride extended-release tablets (XL) are not approved for smoking cessation

treatment; however, bupropion HCl sustained-release is approved for this use. Serious

neuropsychiatric adverse events have been reported in patients taking bupropion for smoking cessation.

These postmarketing reports have included changes in mood (including depression and mania),

psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation,

anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide [see Adverse

Reactions (6.2)]. Some patients who stopped smoking may have been experiencing symptoms of nicotine

withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been

reported in smokers undergoing a smoking cessation attempt without medication. However, some of

these adverse events occurred in patients taking bupropion who continued to smoke.

Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease;

some patients experienced worsening of their psychiatric illnesses. Observe patients for the

occurrence of neuropsychiatric adverse events. Advise patients and caregivers that the patient should

stop taking bupropion hydrochloride extended-release tablets (XL) and contact a healthcare provider

immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the

patient are observed, or if the patient develops suicidal ideation or suicidal behavior. The healthcare

provider should evaluate the severity of the adverse events and the extent to which the patient is

benefiting from treatment, and consider options including continued treatment under closer monitoring,

or discontinuing treatment. In many postmarketing cases, resolution of symptoms after discontinuation of

bupropion was reported. However, the symptoms persisted in some cases; therefore, ongoing

monitoring and supportive care should be provided until symptoms resolve.

5.3 Seizure

Bupropion hydrochloride extended-release tablets (XL) can cause seizure. The risk of seizure is dose-

related. The dose should not exceed 300 mg once daily. Increase the dose gradually. Discontinue

bupropion hydrochloride extended-release tablets (XL) and do not restart treatment if the patient

experiences a seizure.

The risk of seizures is also related to patient factors, clinical situations, and concomitant medications

that lower the seizure threshold. Consider these risks before initiating treatment with bupropion

hydrochloride extended-release tablets (XL). Bupropion hydrochloride extended-release tablets (XL)

are contraindicated in patients with a seizure disorder or conditions that increase the risk of seizure

(e.g., severe head injury, arteriovenous malformation, CNS tumor or CNS infection, severe stroke,

anorexia nervosa or bulimia, or abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and

antiepileptic drugs [see Contraindications (4)]. The following conditions can also increase the risk of

seizure: concomitant use of other medications that lower the seizure threshold (e.g., other bupropion

products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids),

metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia), or use

of illicit drugs (e.g., cocaine) or abuse or misuse of prescription drugs such as CNS stimulants.

Additional predisposing conditions include diabetes mellitus treated with oral hypoglycemic drugs or

insulin, use of anorectic drugs, excessive use of alcohol, benzodiazepines, sedative/hypnotics, or

opiates.

Incidence of Seizure with Bupropion Use

The incidence of seizure with bupropion hydrochloride extended-release tablets (XL) has not been

formally evaluated in clinical trials. In studies using bupropion HCl sustained-release up to 300 mg per

day the incidence of seizure was approximately 0.1% (1/1000 patients). In a large prospective, follow-

up study, the seizure incidence was approximately 0.4% (13/3200) with bupropion HCl immediate-

release in the range of 300 mg to 450 mg per day.

Additional data accumulated for bupropion immediate-release suggests that the estimated seizure

incidence increases almost tenfold between 450 and 600 mg/day. The risk of seizure can be reduced if

the bupropion hydrochloride extended-release tablets (XL) dose does not exceed 450 mg once daily

and the titration rate is gradual.

5.4 Hypertension

Treatment with bupropion hydrochloride extended-release tablets (XL) can result in elevated blood

pressure and hypertension. Assess blood pressure before initiating treatment with bupropion

hydrochloride extended-release tablets (XL), and monitor periodically during treatment. The risk of

hypertension is increased if bupropion hydrochloride extended-release tablets (XL) are used

concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity [see

Contraindications (4)].

Data from a comparative trial of the sustained-release formulation of bupropion HCl, nicotine

transdermal system (NTS), the combination of sustained-release bupropion plus NTS, and placebo as an

aid to smoking cessation suggest a higher incidence of treatment-emergent hypertension in patients

treated with the combination of sustained-release bupropion and NTS. In this trial, 6.1% of subjects

treated with the combination of sustained-release bupropion and NTS had treatment-emergent

hypertension compared to 2.5%, 1.6%, and 3.1% of subjects treated with sustained-release bupropion,

NTS, and placebo, respectively. The majority of these subjects had evidence of pre-existing

hypertension. Three subjects (1.2%) treated with the combination of sustained-release bupropion and

NTS and 1 subject (0.4%) treated with NTS had study medication discontinued due to hypertension

compared with none of the subjects treated with sustained-release bupropion or placebo. Monitoring of

blood pressure is recommended in patients who receive the combination of bupropion and nicotine

replacement.

In the 3 trials of bupropion HCl extended-release in seasonal affective disorder, there were significant

elevations in blood pressure. Hypertension was reported as an adverse reaction for 2% of the

bupropion group (11/537) and none in the placebo group (0/511). In the SAD trials, 2 patients treated

with bupropion discontinued from the study because they developed hypertension. None of the placebo

group discontinued because of hypertension. The mean increase in systolic blood pressure was 1.3

mmHg in the bupropion group and 0.1 mmHg in the placebo group. The difference was statistically

significant (p=0.013). The mean increase in diastolic blood pressure was 0.8 mmHg in the bupropion

group and 0.1 mmHg in the placebo group. The difference was not statistically significant (p=0.075). In

the SAD trials, 82% of patients were treated with 300 mg per day, and 18% were treated with 150 mg

per day. The mean daily dose was 270 mg per day. The mean duration of bupropion exposure was 126

days.

In a clinical trial of bupropion immediate-release in MDD subjects with stable congestive heart failure

(N=36), bupropion was associated with an exacerbation of pre-existing hypertension in 2 subjects,

leading to discontinuation of bupropion treatment. There are no controlled studies assessing the safety

of bupropion in patients with a recent history of myocardial infarction or unstable cardiac disease.

5.5 Activation of Mania/Hypomania

Antidepressant treatment can precipitate a manic, mixed, or hypomanic manic episode. The risk appears

to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. Prior to

initiating bupropion hydrochloride extended-release tablets (XL), screen patients for a history of

bipolar disorder and the presence of risk factors for bipolar disorder (e.g., family history of bipolar

disorder, suicide, or depression). Bupropion hydrochloride extended-release tablets (XL) are not

approved for the treatment of bipolar depression.

5.6 Psychosis and Other Neuropsychiatric Reactions

Depressed patients treated with bupropion have had a variety of neuropsychiatric signs and symptoms,

including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. Some

of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated upon dose

reduction and/or withdrawal of treatment. Discontinue bupropion hydrochloride extended-release

tablets (XL) if these reactions occur.

5.7 Angle-Closure Glaucoma

Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant

drugs including bupropion hydrochloride extended-release tablets (XL) may trigger an angle-closure

attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

5.8 Hypersensitivity Reactions

Anaphylactoid/anaphylactic reactions have occurred during clinical trials with bupropion. Reactions

have been characterized by pruritus, urticaria, angioedema, and dyspnea, requiring medical treatment. In

addition, there have been rare, spontaneous postmarketing reports of erythema multiforme, Stevens-

Johnson Syndrome, and anaphylactic shock associated with bupropion. Instruct patients to discontinue

bupropion hydrochloride extended-release tablets (XL) and consult a healthcare provider if they

develop an allergic or anaphylactoid/anaphylactic reaction (e.g., skin rash, pruritus, hives, chest pain,

edema, and shortness of breath) during treatment.

There are reports of arthralgia, myalgia, fever with rash and other symptoms of serum sickness

suggestive of delayed hypersensitivity.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Suicidal thoughts and behaviors in children, adolescents, and young adults [see Warnings and

Precautions (5.1)]

Neuropsychiatric adverse events and suicide risk in smoking cessation treatment [see Warnings and

Precautions (5.2)]

Seizure [see Warnings and Precautions (5.3)]

Hypertension [see Warnings and Precautions (5.4)]

Activation of mania or hypomania [see Warnings and Precautions (5.5)]

Psychosis and other neuropsychiatric events [see Warnings and Precautions (5.6)]

Angle-Closure Glaucoma [see Warnings and Precautions (5.7)]

Hypersensitivity reactions [see Warnings and Precautions (5.8)]

6.1 Clinical Trials Experience

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.

Commonly Observed Adverse Reactions in Controlled Clinical Trials of Sustained-Release Bupropion

Hydrochloride

Adverse reactions that occurred in at least 5% of patients treated with bupropion HCl sustained-release

(300 mg and 400 mg per day) and at a rate at least twice the placebo rate are listed below.

300 mg/day of bupropion HCl sustained-release: anorexia, dry mouth, rash, sweating, tinnitus, and tremor.

400 mg/day of bupropion HCl sustained-release: abdominal pain, agitation, anxiety, dizziness, dry mouth,

insomnia, myalgia, nausea, palpitation, pharyngitis, sweating, tinnitus, and urinary frequency.

Bupropion hydrochloride extended-release tablets (XL) have been demonstrated to have similar

bioavailability both to the immediate-release and sustained-release formulations of bupropion. The

information included under this subsection and under subsection 6.2 is based primarily on data from

controlled clinical trials with the sustained-release and extended-release formulations of bupropion

hydrochloride.

Major Depressive Disorder

Adverse Reactions Leading to Discontinuation of Treatment with Bupropion HCl Immediate-

Release, Bupropion HCl Sustained-Release, and Bupropion HCl Extended-Release in Major

Depressive Disorder Trials

In placebo-controlled clinical trials with bupropion HCl sustained-release, 4%, 9%, and 11% of the

placebo, 300 mg/day and 400 mg/day groups, respectively, discontinued treatment because of adverse

reactions. The specific adverse reactions leading to discontinuation in at least 1% of the 300 mg/day or

400 mg/day groups and at a rate at least twice the placebo rate are listed in Table 2.

Table 2: Treatment Discontinuation Due to Adverse Reactions in Placebo-Controlled Trials in

MDD

Adverse Reaction

Term

Placebo

(n=385)

Bupropion HCl Sustained-Release

300 mg/day

(n=376)

Bupropion HCl Sustained-Release

400 mg/day

(n=114)

Rash

0.0%

2.4%

0.9%

Nausea

0.3%

0.8%

1.8%

Agitation

0.3%

0.3%

1.8%

Migraine

0.3%

0.0%

1.8%

In clinical trials with bupropion HCl immediate-release, 10% of patients and volunteers discontinued

due to an adverse reaction. Reactions resulting in discontinuation (in addition to those listed above for

the sustained-release formulation) included vomiting, seizures, and sleep disturbances.

Adverse Reactions Occurring at an Incidence of >1% in Patients Treated with Bupropion HCl

Immediate-Release or Bupropion HCl Sustained-Release in MDD

Table 3 summarizes the adverse reactions that occurred in placebo-controlled trials in patients treated

with bupropion HCl sustained-release 300 mg/day and 400 mg/day. These include reactions that

occurred in either the 300 mg or 400 mg group at an incidence of 1% or more and were more frequent

than in the placebo group.

Table 3: Adverse Reactions in Placebo-Controlled Trials in Patients with MDD

Body System/Adverse

Reaction

Placebo

(n=385)

Bupropion HCl Sustained-

Release 300 mg/day

(n=376)

Bupropion HCl Sustained-

Release 400 mg/day

(n=114)

Body (General)

Headache

Infection

Abdominal pain

Asthenia

Chest pain

Pain

Fever

Cardiovascular

Palpitation

Flushing

Migraine

Hot flashes

Digestive

Dry mouth

Nausea

Constipation

Diarrhea

Anorexia

Vomiting

Dysphagia

Musculoskeletal

Myalgia

Arthralgia

Arthritis

Twitch

Nervous System

Insomnia

Dizziness

Agitation

Anxiety

Tremor

Nervousness

Somnolence

Irritability

Memory decreased

Paresthesia

Central nervous system

stimulation

Respiratory

Pharyngitis

Sinusitis

Increased cough

Skin

Sweating

Rash

Pruritus

Urticaria

Special Senses

Tinnitus

Taste perversion

Blurred vision or

diplopia

Urogenital

Urinary frequency

Urinary urgency

Vaginal hemorrhage

Urinary tract infection

The following additional adverse reactions occurred in controlled trials of bupropion HCl immediate-

release (300 to 600 mg per day) at an incidence of at least 1% more frequently than in the placebo group

were: cardiac arrhythmia (5% vs. 4%), hypertension (4% vs. 2%), hypotension (3% vs. 2%), menstrual

complaints (5% vs. 1%), akathisia (2% vs. 1%), impaired sleep quality (4% vs. 2%), sensory disturbance

(4% vs. 3%), confusion (8% vs. 5%), decreased libido (3% vs. 2%), hostility (6% vs. 4%), auditory

disturbance (5% vs. 3%), and gustatory disturbance (3% vs. 1%).

Seasonal Affective Disorder

In placebo-controlled clinical trials in SAD, 9% of patients treated with bupropion hydrochloride

extended-release tablets (XL) and 5% of patients treated with placebo discontinued treatment because of

adverse reactions. The adverse reactions leading to discontinuation in at least 1% of patients treated

with bupropion and at a rate numerically greater than the placebo rate were insomnia (2% vs. <1%) and

headache (1% vs. <1%).

Table 4 summarizes the adverse reactions that occurred in patients treated with bupropion

hydrochloride extended-release tablets (XL) for up to approximately 6 months in 3 placebo-controlled

trials. These include reactions that occurred at an incidence of 2% or more and were more frequent than

in the placebo group.

Table 4: Adverse Reactions in Placebo-Controlled Trials in Patients with SAD

System Organ Class/Preferred Term

Placebo

(n=511)

Bupropion HCl

Extended-Release

(n=537)

Gastrointestinal Disorder

Dry mouth

Incidence based on the number of female patients.

Hyphen denotes adverse reactions occurring in greater than 0 but less than 0.5% of patients.

Nausea

Constipation

Flatulence

Abdominal pain

<1%

Nervous System Disorders

Headache

Dizziness

Tremor

<1%

Infections and Infestations

Nasopharyngitis

Upper respiratory tract infection

Sinusitis

Psychiatric Disorders

Insomnia

Anxiety

Abnormal dreams

Agitation

<1%

Musculoskeletal and Connective Tissue Disorders

Myalgia

Pain in extremity

Respiratory, Thoracic, and Mediastinal Disorders

Cough

General Disorders and Administration Site Conditions

Feeling jittery

Skin and Subcutaneous Tissue Disorders

Rash

Metabolism and Nutrition Disorders

Decreased appetite

Reproductive System and Breast Disorders

Dysmenorrhea

<1%

Ear and Labyrinth Disorders

Tinnitus

<1%

Vascular Disorders

Hypertension

Changes in Body Weight

Table 5 presents the incidence of body weight changes (≥5 lbs) in the short-term MDD trials using

bupropion HCl sustained-release. There was a dose-related decrease in body weight.

Table 5: Incidence of Weight Gain or Weight Loss (≥5 lbs) in MDD

Trials Using Bupropion HCl Sustained-Release

Weight Change

Bupropion HCl

Sustained-Release

300 mg/day

(n=339)

Bupropion HCl

Sustained-Release

400 mg/day

(n=112)

Placebo

(n=347)

Gained >5 lbs

Lost >5 lbs

Table 6 presents the incidence of body weight changes (≥5 lbs) in the 3 SAD trials using bupropion

HCl extended-release. A higher proportion of subjects in the bupropion group (23%) had a weight loss

≥5 lbs, compared to the placebo group (11%). These were relatively long-term trials (up to 6 months).

Table 6: Incidence of Weight Gain or Weight Loss (≥5 lbs) in SAD Trials Using Bupropion

HCl Extended-Release

Weight Change

Bupropion HCl

Extended-Release

150 to 300 mg/day

(n=537)

Placebo

(n=511)

Gained >5 lbs

Lost >5 lbs

6.2 Postmarketing Experience

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

hydrochloride extended-release tablets (XL). 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..

Body (General)

Chills, facial edema, edema, peripheral edema, musculoskeletal chest pain, photosensitivity, and

malaise.

Cardiovas cular

Postural hypotension, hypertension, stroke, vasodilation, syncope, complete atrioventricular block,

extrasystoles, myocardial infarction, phlebitis, and pulmonary embolism.

Diges tive

Abnormal liver function, bruxism, gastric reflux, gingivitis, glossitis, increased salivation, jaundice,

mouth ulcers, stomatitis, thirst, edema of tongue, colitis, esophagitis, gastrointestinal hemorrhage, gum

hemorrhage, hepatitis, intestinal perforation, liver damage, pancreatitis, and stomach ulcer.

Endocrine

Hyperglycemia, hypoglycemia, and syndrome of inappropriate antidiuretic hormone secretion.

Hemic and Lymphatic

Ecchymosis, anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia.

Altered PT and/or INR, associated with hemorrhagic or thrombotic complications, were observed when

bupropion was coadministered with warfarin.

Metabolic and Nutritional

Glycosuria.

Mus culos keletal

Leg cramps, fever/rhabdomyolysis, and muscle weakness.

Nervous System

Abnormal coordination, depersonalization, emotional lability, hyperkinesia, hypertonia, hypesthesia,

vertigo, amnesia, ataxia, derealization, abnormal electroencephalogram (EEG), aggression, akinesia,

aphasia, coma, dysarthria, dyskinesia, dystonia, euphoria, extrapyramidal syndrome, hypokinesia,

increased libido, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking

tardive dyskinesia.

Res piratory

Bronchospasm and pneumonia.

Skin

Maculopapular rash, alopecia, angioedema, exfoliative dermatitis, and hirsutism.

Special Senses

Accommodation abnormality, dry eye, deafness, increased intraocular pressure, angle-closure

glaucoma, and mydriasis.

Urogenital

Impotence, polyuria, prostate disorder, abnormal ejaculation, cystitis, dyspareunia, dysuria,

gynecomastia, menopause, painful erection, salpingitis, urinary incontinence, urinary retention, and

vaginitis.

7 DRUG INTERACTIONS

7.1 Potential for Other Drugs to Affect Bupropion Hydrochloride Extended-Release Tablets (XL)

Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists

for drug interactions between bupropion hydrochloride extended-release tablets (XL) and drugs that are

inhibitors or inducers of CYP2B6.

Inhibitors of CYP2B6

Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures

but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of bupropion

hydrochloride extended-release tablets (XL) may be necessary when coadministered with CYP2B6

inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)].

Inducers of CYP2B6

Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and

hydroxybupropion exposure. Dosage increase of bupropion hydrochloride extended-release tablets

(XL) may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not

exceed the maximum recommended dose [see Clinical Pharmacology (12.3)].

Carbamazepine, Phenobarbital, Phenytoin: While not systemically studied, these drugs may induce

metabolism of bupropion and may decrease bupropion exposure [see Clinical Pharmacology (12.3)]. If

bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of

bupropion, but the maximum recommended dose should not be exceeded.

7.2 Potential for Bupropion Hydrochloride Extended-Release Tablets (XL) to Affect Other Drugs

Drugs Metabolized by CYP2D6

Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are

CYP2D6 inhibitors. Therefore, coadministration of bupropion hydrochloride extended-release tablets

(XL) with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are

substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline,

imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g., haloperidol,

risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g.,

propafenone, and flecainide). When used concomitantly with bupropion hydrochloride extended-release

tablets (XL), it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for

drugs with a narrow therapeutic index.

Drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen), theoretically

could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as

bupropion. Patients treated concomitantly with bupropion hydrochloride extended-release tablets (XL)

and such drugs may require increased doses of the drug [see Clinical Pharmacology (12.3)].

7.3 Drugs That Lower Seizure Threshold

Use extreme caution when coadministering bupropion hydrochloride extended-release tablets (XL) with

other drugs that lower the seizure threshold (e.g., other bupropion products, antipsychotics,

antidepressants, theophylline, or systemic corticosteroids). Use low initial doses of bupropion

hydrochloride extended-release tablets (XL) and increase the dose gradually [see Warnings and

Precautions (5.3)].

7.4 Dopaminergic Drugs (Levodopa and Amantadine)

Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported

when bupropion was coadministered with levodopa or amantadine. Adverse reactions have included

restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. It is presumed that the

toxicity results from cumulative dopamine agonist effects. Use caution when administering bupropion

hydrochloride extended-release tablets (XL) concomitantly with these drugs.

7.5 Use with Alcohol

In postmarketing experience, there have been rare reports of adverse neuropsychiatric events or

reduced alcohol tolerance in patients who were drinking alcohol during treatment with bupropion

hydrochloride extended-release tablets (XL). The consumption of alcohol during treatment with

bupropion hydrochloride extended-release tablets (XL) should be minimized or avoided

7.6 MAO Inhibitors

Bupropion inhibits the reuptake of dopamine and norepinephrine. Concomitant use of MAOIs and

bupropion is contraindicated because there is an increased risk of hypertensive reactions if bupropion

is used concomitantly with MAOIs. Studies in animals demonstrate that the acute toxicity of bupropion is

enhanced by the MAO inhibitor phenelzine. At least 14 days should elapse between discontinuation of

an MAOI intended to treat depression and initiation of treatment with bupropion hydrochloride extended-

release tablets (XL). Conversely, at least 14 days should be allowed after stopping bupropion

hydrochloride extended-release tablets (XL) before starting an MAOI antidepressant [see Dosage and

Administration (2.8, 2.9) and Contraindications (4)].

7.7 Drug-Laboratory Test Interactions

False-positive urine immunoassay screening tests for amphetamines have been reported in patients

taking bupropion. This is due to lack of specificity of some screening tests. False-positive test results

may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas

chromatography/mass spectrometry, will distinguish bupropion from amphetamines.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

Risk Summary

Data from epidemiological studies including pregnant women exposed to bupropion in the first

trimester indicate no increased risk of congenital malformations overall. All pregnancies regardless of

drug exposure have a background rate of 2% to 4% for major malformations and 15% to 20% for

pregnancy loss. No clear evidence of teratogenic activity was found in reproductive developmental

studies conducted in rats and rabbits. However, in rabbits, slightly increased incidences of fetal

malformations and skeletal variations were observed at doses approximately equal to the maximum

recommended human dose (MRHD) and greater and decreased fetal weights were seen at doses twice

the MRHD and greater. Bupropion hydrochloride extended-release tablets (XL) should be used during

pregnancy only if the potential benefit justifies the potential risk to the fetus.

Clinical Considerations

Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant

medications during pregnancy and postpartum.

Human Data

Data from an international bupropion Pregnancy Registry (675 first trimester exposures) and a

retrospective cohort study using the United Healthcare database (1,213 first trimester exposures) did

not show an increased risk for malformations overall.

No increased risk for cardiovascular malformations overall has been observed after bupropion

exposure during the first trimester. The prospectively observed rate of cardiovascular malformations in

pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry

was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is

similar to the background rate of cardiovascular malformations (approximately 1%). Data from the

United Healthcare database and a case-controlled study (6,853 infants with cardiovascular

malformations and 5,753 with non-cardiovascular malformations) from the National Birth Defects

Prevention Study (NBDPS) did not show an increased risk for cardiovascular malformations overall

after bupropion exposure during the first trimester.

Study findings on bupropion exposure during the first trimester and risk left ventricular outflow tract

obstruction (LVOTO) are inconsistent and do not allow conclusions regarding possible association.

The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found

increased risk for LVOTO (n = 10; adjusted OR = 2.6; 95% CI 1.2, 5.7) and the Slone Epidemiology

case control study did not find increased risk for LVOTO.

Study findings on bupropion exposure during the first trimester and risk for ventricular septal defect

(VSD) are inconsistent and do not allow conclusions regarding a possible association. The Slone

Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion

exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0) but did not find an increased risk for any other

cardiovascular malformations studied (including LVOTO as above). The NBDPS and United Healthcare

database study did not find an association between first trimester maternal bupropion exposure and VSD.

For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases,

inconsistent findings among studies, and the potential for chance findings from multiple comparisons in

case control studies.

Animal Data

In studies conducted in rats and rabbits, bupropion was administered orally at doses of up to 450 and 150

mg/kg/day, respectively (approximately 11 and 7 times the MRHD, respectively, on a mg/m

basis),

during the period of organogenesis. No clear evidence of teratogenic activity was found in either

species; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations

were observed at the lowest dose tested (25 mg/kg/day, approximately equal to the MRHD on a mg/m

basis) and greater. Decreased fetal weights were observed at 50 mg/kg and greater. When rats were

administered bupropion at oral doses of up to 300 mg/kg/day (approximately 7 times the MRHD on a

mg/m

basis) prior to mating and throughout pregnancy and lactation, there were no apparent adverse

effects on offspring development.

8.3 Nursing Mothers

Bupropion and its metabolites are present in human milk. In a lactation study of ten women, levels of

orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily

infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2%

of the maternal weight-adjusted dose. Exercise caution when bupropion hydrochloride extended-

release tablets (XL) are administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness in the pediatric population have not been established. When considering the

use of bupropion hydrochloride extended-release tablets (XL) in a child or adolescent, balance the

potential risks with the clinical need [see Boxed Warning and Warnings and Precautions (5.1)].

8.5 Geriatric Use

Of the approximately 6000 patients who participated in clinical trials with bupropion hydrochloride

sustained-release tablets (depression and smoking cessation studies), 275 were ≥65 years old and 47

were ≥75 years old. In addition, several hundred patients ≥65 years of age participated in clinical trials

using the immediate-release formulation of bupropion hydrochloride (depression studies). No overall

differences in safety or effectiveness were observed between these subjects and younger subjects.

Reported clinical experience has not identified differences in responses between the elderly and

younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized

and excreted by the kidneys. The risk of adverse reactions may be greater in patients with impaired renal

function. Because elderly patients are more likely to have decreased renal function, it may be necessary

to consider this factor in dose selection; it may be useful to monitor renal function [see Dosage and

Administration (2.7), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

8.6 Renal Impairment

Consider a reduced dose and/or dosing frequency of bupropion hydrochloride extended-release tablets

(XL) in patients with renal impairment (glomerular filtration rate: <90 mL/min). Bupropion and its

metabolites are cleared renally and may accumulate in such patients to a greater extent than usual.

Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see

Dosage and Administration (2.7) and Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum

bupropion hydrochloride extended-release tablets (XL) dose is 150 mg every other day. In patients with

mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of

dosing [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3)].

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Bupropion is not a controlled substance.

9.2 Abuse

Humans

Controlled clinical studies of bupropion HCl immediate-release conducted in normal volunteers, in

subjects with a history of multiple drug abuse, and in depressed patients demonstrated an increase in

motor activity and agitation/excitement.

In a population of individuals experienced with drugs of abuse, a single dose of 400 mg bupropion

produced mild amphetamine-like activity as compared to placebo on the Morphine-Benzedrine Subscale

of the Addiction Research Center Inventories (ARCI), and a score intermediate between placebo and

amphetamine on the Liking Scale of the ARCI. These scales measure general feelings of euphoria and

drug desirability.

Findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs.

Nonetheless, evidence from single-dose studies does suggest that the recommended daily dosage of

bupropion when administered in divided doses is not likely to be significantly reinforcing to

amphetamine or CNS stimulant abusers. However, higher doses (that could not be tested because of the

risk of seizure) might be modestly attractive to those who abuse CNS stimulant drugs.

Bupropion hydrochloride extended-release tablets (XL) are intended for oral use only. The inhalation

of crushed tablets or injection of dissolved bupropion has been reported. Seizures and/or cases of death

have been reported when bupropion has been administered intranasally or by parenteral injection.

Animals

Studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions

common to psychostimulants. In rodents, it has been shown to increase locomotor activity, elicit a mild

stereotyped behavioral response, and increase rates of responding in several schedule-controlled

behavior paradigms. In primate models assessing the positive reinforcing effects of psychoactive

drugs, bupropion was self-administered intravenously. In rats, bupropion produced amphetamine-like

and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize

the subjective effects of psychoactive drugs.

10 OVERDOSAGE

10.1 Human Overdose Experience

Overdoses of up to 30 grams or more of bupropion have been reported. Seizure was reported in

approximately one third of all cases. Other serious reactions reported with overdoses of bupropion

alone included hallucinations, loss of consciousness, sinus tachycardia, and ECG changes such as

conduction disturbances or arrhythmias. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor,

coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug

overdoses.

Although most patients recovered without sequelae, deaths associated with overdoses of bupropion

alone have been reported in patients ingesting large doses of the drug. Multiple uncontrolled seizures,

bradycardia, cardiac failure, and cardiac arrest prior to death were reported in these patients.

10.2 Overdosage Management

Consult a Certified Poison Control Center for up-to-date guidance and advice. Telephone numbers for

certified poison control centers are listed in the Physicians’ Desk Reference (PDR). Call 1-800-222-

1222 or refer to www.poison.org.

There are no known antidotes for bupropion. In case of an overdose, provide supportive care, including

close medical supervision and monitoring. Consider the possibility of multiple drug overdose.

11 DESCRIPTION

Bupropion hydrochloride extended-release tablets (XL), an antidepressant of the aminoketone class, is

chemically unrelated to tricyclic, tetracyclic, selective serotonin reuptake inhibitor, or other known

antidepressant agents. Its structure closely resembles that of diethylpropion; it is related to

phenylethylamines. It is designated as (±)-1-(3-chorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone

hydrochloride. The molecular weight is 276.2. The molecular formula is C

ClNOHCl.

Bupropion hydrochloride powder is white, crystalline, and highly soluble in water. It has a bitter taste

and produces the sensation of local anesthesia on the oral mucosa. The structural formula is:

Bupropion hydrochloride extended-release tablets (XL) are supplied for oral administration as 300 mg

white to off-white extended-release tablets. Each tablet contains the labeled amount of bupropion

hydrochloride and the inactive ingredients: alcohol, ethylcellulose, hydrochloric acid, hydroxypropyl

cellulose, hypromellose, methacrylic acid and ethyl acrylate copolymer, polyethylene

glycol, povidone, purified water, silicon dioxide, stearic acid and talc. The tablets are printed with

edible black ink, which contains ferrosoferric oxide, hypromellose, propylene glycol, and purified

water.

The insoluble shell of the extended-release tablet may remain intact during gastrointestinal transit and is

eliminated in the feces.

FDA approved dissolution test specifications differ from the USP.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism of action of bupropion is unknown, as is the case with other antidepressants. However,

it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms. Bupropion

is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine and does not inhibit

monoamine oxidase or the reuptake of serotonin.

12.3 Pharmacokinetics

Bupropion is a racemic mixture. The pharmacologic activity and pharmacokinetics of the individual

enantiomers have not been studied.

Following chronic dosing, the mean steady-state plasma concentration of bupropion was reached within

8 days. The mean elimination half-life (±SD) of bupropion is 21 (±9) hours.

In a study comparing 14-day dosing with bupropion hydrochloride extended-release tablets (XL), 300

mg once-daily to the immediate-release formulation of bupropion at 100 mg 3 times daily, equivalence

was demonstrated for peak plasma concentration and area under the curve for bupropion and the three

metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion). Additionally, in a

study comparing 14-day dosing with bupropion hydrochloride extended-release tablets (XL) 300 mg

once daily to the sustained-release formulation of bupropion at 150 mg 2 times daily, equivalence was

demonstrated for peak plasma concentration and area under the curve for bupropion and the three

metabolites.

Abs orption

Following single oral administration of bupropion hydrochloride extended-release tablets (XL) to

healthy volunteers, the median time to peak plasma concentrations for bupropion was approximately 5

hours. The presence of food did not affect the peak concentration or area under the curve of bupropion.

Dis tribution

In vitro tests show that bupropion is 84% bound to human plasma proteins at concentrations up to 200

mcg/mL. The extent of protein binding of the hydroxybupropion metabolite is similar to that for

bupropion, whereas the extent of protein binding of the threohydrobupropion metabolite is about half

that of bupropion.

Metabolis m

Bupropion is extensively metabolized in humans. Three metabolites are active: hydroxybupropion,

which is formed via hydroxylation of the tert-butyl group of bupropion, and the amino-alcohol isomers

threohydrobupropion and erythrohydrobupropion, which are formed via reduction of the carbonyl

group. In vitro findings suggest that CYP2B6 is the principal isoenzyme involved in the formation of

hydroxybupropion, while cytochrome P450 enzymes are not involved in the formation of

threohydrobupropion. Oxidation of the bupropion side chain results in the formation of a glycine

conjugate of meta-chlorobenzoic acid, which is then excreted as the major urinary metabolite. The

potency and toxicity of the metabolites relative to bupropion have not been fully characterized.

However, it has been demonstrated in an antidepressant screening test in mice that hydroxybupropion is

one half as potent as bupropion, while threohydrobupropion and erythrohydrobupropion are 5-fold less

potent than bupropion. This may be of clinical importance, because the plasma concentrations of the

metabolites are as high or higher than those of bupropion.

At steady state, peak plasma concentration of hydroxybupropion occurred approximately 7 hours after

administration of bupropion hydrochloride extended-release tablets (XL), and it was approximately 7

times the peak level of the parent drug. The elimination half-life of hydroxybupropion is approximately

20 (±5) hours, and its AUC at steady state is about 13 times that of bupropion. The times to peak

concentrations for the erythrohydrobupropion and threohydrobupropion metabolites are similar to that

of hydroxybupropion. However, the elimination half-lives of erythrohydrobupropion and

threohydrobupropion are longer, approximately 33 (±10) and 37 (±13) hours, respectively, and steady-

state AUCs were 1.4 and 7 times that of bupropion, respectively.

Bupropion and its metabolites exhibit linear kinetics following chronic administration of 300 to 450

mg/day.

Elimination

Following oral administration of 200 mg of

C-bupropion in humans, 87% and 10% of the radioactive

dose were recovered in the urine and feces, respectively. Only 0.5% of the oral dose was excreted as

unchanged bupropion.

Population Subgroups

Factors or conditions altering metabolic capacity (e.g., liver disease, congestive heart failure [CHF],

age, concomitant medications, etc.) or elimination may be expected to influence the degree and extent of

accumulation of the active metabolites of bupropion. The elimination of the major metabolites of

bupropion may be affected by reduced renal or hepatic function, because they are moderately polar

compounds and are likely to undergo further metabolism or conjugation in the liver prior to urinary

excretion.

Renal Impairment

There is limited information on the pharmacokinetics of bupropion in patients with renal impairment. An

inter-trial comparison between normal subjects and subjects with end-stage renal failure demonstrated

that the parent drug C

and AUC values were comparable in the 2 groups, whereas the

hydroxybupropion and threohydrobupropion metabolites had a 2.3- and 2.8-fold increase, respectively,

in AUC for subjects with end-stage renal failure. A second study, comparing normal subjects and

subjects with moderate-to-severe renal impairment (GFR 30.9 ± 10.8 mL/min) showed that after a single

150 mg dose of sustained-release bupropion, exposure to bupropion was approximately 2-fold higher

in subjects with impaired renal function, while levels of the hydroxybupropion and

threo/erythrohydrobupropion (combined) metabolites were similar in the 2 groups. Bupropion is

extensively metabolized in the liver to active metabolites, which are further metabolized and

subsequently excreted by the kidneys. The elimination of the major metabolites of bupropion may be

reduced by impaired renal function. Bupropion hydrochloride extended-release tablets (XL) should be

used with caution in patients with renal impairment, and a reduced frequency and/or dose should be

considered [see Dosage and Administration (2.7) and Use in Specific Populations (8.6) ].

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of bupropion was characterized in 2 single-

dose trials, one in subjects with alcoholic liver disease and one in subjects with mild to severe

cirrhosis. The first trial demonstrated that the half-life of hydroxybupropion was significantly longer in

8 subjects with alcoholic liver disease than in 8 healthy volunteers (32±14 hours versus 21±5 hours,

respectively). Although not statistically significant, the AUCs for bupropion and hydroxybupropion

were more variable and tended to be greater (by 53% to 57%) in patients with alcoholic liver disease.

The differences in half-life for bupropion and the other metabolites in the 2 groups were minimal.

The second trial demonstrated no statistically significant differences in the pharmacokinetics of

bupropion and its active metabolites in 9 subjects with mild to moderate hepatic cirrhosis compared to 8

healthy volunteers. However, more variability was observed in some of the pharmacokinetic parameters

for bupropion (AUC, C

, and T

) and its active metabolites (t

) in subjects with mild to moderate

hepatic cirrhosis. In addition, in patients with severe hepatic cirrhosis, the bupropion C

and AUC

were substantially increased (mean difference: by approximately 70% and 3-fold, respectively) and

more variable when compared to values in healthy volunteers; the mean bupropion half-life was also

longer (29 hours in subjects with severe hepatic cirrhosis vs. 19 hours in healthy subjects). For the

metabolite hydroxybupropion, the mean C

was approximately 69% lower. For the combined amino-

alcohol isomers threohydrobupropion and erythrohydrobupropion, the mean C

was approximately

31% lower. The mean AUC increased by about 1½-fold for hydroxybupropion and about 2½-fold for

threo/erythrohydrobupropion. The median T

was observed 19 hours later for hydroxybupropion

and 31 hours later for threo/erythrohydrobupropion. The mean half-lives for hydroxybupropion and

threo/erythrohydrobupropion were increased 5- and 2-fold, respectively, in patients with severe hepatic

cirrhosis compared to healthy volunteers [see Dosage and Administration (2.6) and Use in Specific

Populations (8.7)].

Left Ventricular Dysfunction

During a chronic dosing study with bupropion in 14 depressed patients with left ventricular dysfunction

(history of CHF or an enlarged heart on x-ray), there was no apparent effect on the pharmacokinetics of

bupropion or its metabolites, compared to healthy volunteers.

Age

The effects of age on the pharmacokinetics of bupropion and its metabolites have not been fully

characterized, but an exploration of steady-state bupropion concentrations from several depression

efficacy studies involving patients dosed in a range of 300 to 750 mg/day, on a 3 times daily schedule,

revealed no relationship between age (18 to 83 years) and plasma concentration of bupropion. A single-

dose pharmacokinetic study demonstrated that the disposition of bupropion and its metabolites in elderly

subjects was similar to that in younger subjects. These data suggest that there is no prominent effect of

age on bupropion concentration; however, another single- and multiple-dose pharmacokinetic study

suggested that the elderly are at increased risk for accumulation of bupropion and its metabolites [see

Use in Specific Populations (8.5)].

Gender

A single-dose study involving 12 healthy male and 12 healthy female volunteers revealed no sex-related

differences in the pharmacokinetic parameters of bupropion. In addition, pooled analysis of bupropion

pharmacokinetic data from 90 healthy male and 90 healthy female volunteers revealed no sex-related

differences in the peak plasma concentrations of bupropion. The mean systemic exposure (AUC) was

approximately 13% higher in male volunteers compared to female volunteers.

Smokers

The effects of cigarette smoking on the pharmacokinetics of bupropion hydrochloride were studied in

34 healthy male and female volunteers; 17 were chronic cigarette smokers and 17 were nonsmokers.

Following oral administration of a single 150 mg dose of bupropion, there was no statistically

significant difference in C

, half-life, T

, AUC, or clearance of bupropion or its active

metabolites between smokers and nonsmokers.

Drug Interactions

Potential for Other Drugs to Affect Bupropion Hydrochloride Extended-Release Tablets (XL)

In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6.

Therefore, the potential exists for drug interactions between bupropion hydrochloride extended-

release tablets (XL) and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies

suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir inhibit the hydroxylation

of bupropion.

Inhibitors of CYP2B6

Ticlopidine and Clopidogrel: In a study in healthy male volunteers, clopidogrel 75 mg once daily or

ticlopidine 250 mg twice daily increased exposures (C

and AUC) of bupropion by 40% and 60%

for clopidogrel, by 38% and 85% for ticlopidine, respectively. The exposures of hydroxybupropion

were decreased.

Prasugrel: In healthy subjects, prasugrel increased bupropion C

and AUC values by 14% and 18%,

respectively, and decreased C

and AUC values of hydroxybupropion by 32% and 24%,

respectively.

Cimetidine: Following oral administration of bupropion 300 mg with and without cimetidine 800 mg in

24 healthy young male volunteers, the pharmacokinetics of bupropion and hydroxybupropion were

unaffected. However, there were 16% and 32% increases in the AUC and C

, respectively, of the

combined moieties of threohydrobupropion and erythrohydrobupropion.

Citalopram: Citalopram did not affect the pharmacokinetics of bupropion and its three metabolites.

Inducers of CYP2B6

Ritonavir and Lopinavir: In a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and

of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite

was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion

decreased by 48%. In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the

AUC and C

of bupropion by 66% and 62%, respectively. The exposure of the hydroxybupropion

metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the

erythrohydrobupropion decreased by 68%.

In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion

AUC and C

by 57%. The AUC and C

of hydroxybupropion metabolite were decreased by 50%

and 31%, respectively.

Efavirenz: In a study of healthy volunteers, efavirenz 600 mg once daily for 2 weeks reduced the AUC

and C

of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion

was unchanged, whereas C

of hydroxybupropion was increased by 50%.

Carbamazepine, Phenobarbital, Phenytoin: While not systematically studied, these drugs may induce the

metabolism of bupropion.

Potential for Bupropion Hydrochloride Extended-Release Tablets (XL) to Affect Other Drugs

Animal data indicated that bupropion may be an inducer of drug-metabolizing enzymes in humans. In a

study of 8 healthy male volunteers, following a 14-day administration of bupropion 100 mg three times

per day, there was no evidence of induction of its own metabolism. Nevertheless, there may be the

potential for clinically important alterations of blood levels of coadministered drugs.

Drugs Metabolized by CYP2D6

In vitro, bupropion and hydroxybupropion are CYP2D6 inhibitors. In a clinical study of 15 male subjects

(ages 19 to 35 years) who were extensive metabolizers of CYP2D6, bupropion given as 150 mg twice

daily followed by a single dose of 50 mg desipramine increased the C

, AUC, and T

desipramine by an average of approximately 2-, 5-, and 2-fold, respectively. The effect was present for

at least 7 days after the last dose of bupropion. Concomitant use of bupropion with other drugs

metabolized by CYP2D6 has not been formally studied.

Citalopram: Although citalopram is not primarily metabolized by CYP2D6, in one study bupropion

increased the C

and AUC of citalopram by 30% and 40%, respectively.

Lamotrigine: Multiple oral doses of bupropion had no statistically significant effects on the single-dose

pharmacokinetics of lamotrigine in 12 healthy volunteers.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Lifetime carcinogenicity studies were performed in rats and mice at doses up to 300 and 150 mg/kg/day

bupropion hydrochloride, respectively. These doses are approximately 7 and 2 times the maximum

recommended human dose (MRHD), respectively, on a mg/m

basis. In the rat study there was an

increase in nodular proliferative lesions of the liver at doses of 100 to 300 mg/kg/day of bupropion

hydrochloride (approximately 2 to 7 times the MRHD on a mg/m

basis); lower doses were not tested.

The question of whether or not such lesions may be precursors of neoplasms of the liver is currently

unresolved. Similar liver lesions were not seen in the mouse study, and no increase in malignant tumors

of the liver and other organs was seen in either study.

Bupropion produced a positive response (2 to 3 times control mutation rate) in 2 of 5 strains in one

Ames bacterial mutagenicity assay, but was negative in another. Bupropion produced an increase in

chromosomal aberrations in 1 of 3 in vivo rat bone marrow cytogenetic studies.

A fertility study in rats at doses up to 300 mg/kg/day revealed no evidence of impaired fertility.

14 CLINICAL STUDIES

14.1 Major Depressive Disorder

The efficacy of bupropion in the treatment of major depressive disorder was established with the

immediate-release formulation of bupropion hydrochloride in two 4-week, placebo-controlled trials in

adult inpatients with MDD and in one 6-week, placebo-controlled trial in adult outpatients with MDD. In

the first study, the bupropion dose range was 300 mg to 600 mg per day administered in 3 divided

doses; 78% of patients were treated with doses of 300 mg to 450 mg per day. The trial demonstrated

the efficacy of bupropion as measured by the Hamilton Depression Rating Scale (HAMD) total score,

the HAMD depressed mood item (item 1), and the Clinical Global Impressions-Severity Scale (CGI-S).

The second study included 2 fixed doses of bupropion (300 mg and 450 mg per day) and placebo. This

trial demonstrated the efficacy of bupropion for only the 450 mg dose. The efficacy results were

significant for the HAMD total score and the CGI-S severity score, but not for HAMD item 1. In the

third study, outpatients were treated with bupropion 300 mg per day. This study demonstrated the

efficacy of bupropion as measured by the HAMD total score, the HAMD item 1, the Montgomery-

Asberg Depression Rating Scale (MADRS), the CGI-S score, and the CGI-Improvement Scale (CGI-I)

score.

A longer-term, placebo-controlled, randomized withdrawal trial demonstrated the efficacy of bupropion

HCl sustained-release in the maintenance treatment of MDD. The trial included adult outpatients meeting

DSM-IV criteria for MDD, recurrent type, who had responded during an 8-week open-label trial of

bupropion 300 mg per day. Responders were randomized to continuation of bupropion 300 mg per day

or placebo for up to 44 weeks of observation for relapse. Response during the open-label phase was

defined as a CGI-Improvement Scale score of 1 (very much improved) or 2 (much improved) for each

of the final 3 weeks. Relapse during the double-blind phase was defined as the investigator’s judgment

that drug treatment was needed for worsening depressive symptoms. Patients in the bupropion group

experienced significantly lower relapse rates over the subsequent 44 weeks compared to those in the

placebo group.

Although there are no independent trials demonstrating the efficacy of bupropion hydrochloride

extended-release tablets (XL) in the acute treatment of MDD, studies have demonstrated similar

bioavailability between the immediate-, sustained-, and extended-release formulations of bupropion HCl

under steady-state conditions (i.e., the exposures [C

and AUC] for bupropion and its metabolites are

similar among the 3 formulations).

14.2 Seasonal Affective Disorder

The efficacy of bupropion hydrochloride extended-release tablets (XL) in the prevention of seasonal

major depressive episodes associated with SAD was established in 3 randomized, double-blind,

placebo-controlled trials in adult outpatients with a history of MDD with an autumn-winter seasonal

pattern (as defined by DSM-IV criteria). Bupropion treatment was initiated prior to the onset of

symptoms in the autumn (September to November). Treatment was discontinued following a 2-week

taper that began during the first week of spring (fourth week of March), resulting in a treatment duration

of approximately 4 to 6 months for the majority of patients. Patients were randomized to treatment with

bupropion hydrochloride extended-release tablets (XL) or placebo. The initial bupropion dose was 150

mg once daily for 1 week, followed by up-titration to 300 mg once daily. Patients who were deemed by

the investigator to be unlikely or unable to tolerate 300 mg once daily were allowed to remain on, or

had their dose reduced to, 150 mg once daily. The mean bupropion doses in the 3 trials ranged from 257

mg to 280 mg per day. Approximately 59% of patients continued in the study for 3 to 6 months; 26%

continued for <3 months, 15% continued for >6 months.

To enter the trials, patients must have had a low level of depressive symptoms, as demonstrated by a

score of <7 on the Hamilton Depression Rating Scale-17 (HAMD17) and a HAMD24 score of <14. The

primary efficacy measure was the Structured Interview Guide for the Hamilton Depression Rating

Scale, Seasonal Affective Disorders (SIGH-SAD), which is identical to the HAMD24. The SIGH-SAD

consists of the HAMD17 plus 7 items specifically assessing core symptoms of seasonal affective

disorder: social withdrawal, weight gain, increased appetite, increased eating, carbohydrate craving,

hypersomnia, and fatigability. The primary efficacy endpoint was the onset of a seasonal major

depressive episode. The criteria for defining an episode included: 1) the investigator’s judgment that a

major depressive episode had occurred or that the patient required intervention for depressive

symptoms, or 2) a SIGH-SAD score of >20 on 2 consecutive weeks. The primary analysis was a

comparison of depression-free rates between the bupropion and placebo groups.

In these 3 trials, the percentage of patients who were depression-free (did not have an episode of MDD)

at the end of treatment was significantly higher in the bupropion group than in the placebo group: 81.4%

vs. 69.7%, 87.2% vs. 78.7%, and 84.0% vs. 69.0% for Trials 1, 2 and 3, respectively. For the 3 trials

combined, the depression-free rate was 84.3% versus 72.0% in the bupropion and placebo group,

respectively.

16 HOW SUPPLIED/STORAGE AND HANDLING

Bupropion hydrochloride extended-release tablets (XL), 300 mg of bupropion hydrochloride, are white

to off-white, round tablets printed with "T011". They are supplied as follows:

Bottles of 30 tablets NDC 71765-002-03

Bottles of 90 tablets NDC 71765-002-09

Bottles of 500 tablets NDC 71765-002-50.

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

Room Temperature]. Protect from light.

Bupropion hydrochloride extended-release tablets (XL) may have an odor.

17 PATIENT COUNSELING INFORMATION

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

Inform patients, their families, and their caregivers about the benefits and risks associated with treatment

with bupropion hydrochloride extended-release tablets (XL) and counsel them in its appropriate use.

A patient Medication Guide about “Antidepressant Medicines, Depression and Other Serious Mental

Illnesses, and Suicidal Thoughts or Actions,” “Quitting Smoking, Quit-Smoking Medications, Changes

in Thinking and Behavior, Depression, and Suicidal Thoughts or Actions,” and “What Other Important

Information Should I Know About Bupropion Hydrochloride Extended-Release Tablets (XL)?” is

available for bupropion hydrochloride extended-release tablets (XL). Instruct patients, their families,

and their caregivers to read the Medication Guide and 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.

Advise patients regarding the following issues and to alert their prescriber if these occur while taking

bupropion hydrochloride extended-release tablets (XL).

Suicidal Thoughts and Behaviors

Instruct patients, their families, and/or their caregivers to be alert to the emergence of anxiety, agitation,

panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor

restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and

suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or

down. Advise families and caregivers of patients to observe for the emergence of such symptoms on a

day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s

prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the

patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for

suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the

medication.

Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation Treatment

Although bupropion hydrochloride extended-release tablets (XL) are not indicated for smoking

cessation treatment, it contains the same active ingredient as ZYBAN

which is approved for this use.

Inform patients that some patients have experienced changes in mood (including depression and mania),

psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation,

anxiety, and panic, as well as suicidal ideation and suicide when attempting to quit smoking while taking

bupropion. Instruct patients to discontinue bupropion hydrochloride extended-release tablets (XL) and

contact a healthcare professional if they experience such symptoms [see Warnings and Precautions (5.2)

and Adverse Reactions (6.2)] .

Severe Allergic Reactions

Educate patients on the symptoms of hypersensitivity and to discontinue bupropion hydrochloride

extended-release tablets (XL) if they have a severe allergic reaction.

Seizure

Instruct patients to discontinue and not restart bupropion hydrochloride extended-release tablets (XL) if

they experience a seizure while on treatment. Advise patients that the excessive use or the abrupt

discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the

risk of seizure. Advise patients to minimize or avoid the use of alcohol.

Angle-Closure Glaucoma

Patients should be advised that taking bupropion hydrochloride extended-release tablets (XL) can cause

mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure

glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure

glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a

risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are

susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are

susceptible [see Warnings and Precautions (5.7)].

Bupropion-Containing Products

Educate patients that bupropion hydrochloride extended-release tablets (XL) contain the same active

ingredient (bupropion) found in ZYBAN

, which is used as an aid to smoking cessation treatment, and

that bupropion hydrochloride extended-release tablets should not be used in combination with ZYBAN

or any other medications that contain bupropion hydrochloride (such as WELLBUTRIN

SR, the

sustained-release formulation, WELLBUTRIN

, the immediate-release formulation, and APLENZIN

, a bupropion hydrobromide formulation). In addition, there are a number of generic bupropion HCl

products for the immediate, sustained, and extended-release formulations.

Potential for Cognitive and Motor Impairment

Advise patients that any CNS-active drug like bupropion hydrochloride extended-release tablets (XL)

may impair their ability to perform tasks requiring judgment or motor and cognitive skills. Advise

patients that until they are reasonably certain that bupropion hydrochloride extended-release tablets

(XL) do not adversely affect their performance, they should refrain from driving an automobile or

operating complex, hazardous machinery. Bupropion hydrochloride extended-release tablets (XL)

treatment may lead to decreased alcohol tolerance.

Concomitant Medications

Counsel patients to notify their healthcare provider if they are taking or plan to take any prescription or

over-the-counter drugs, because bupropion hydrochloride extended-release tablets (XL) and other

drugs may affect each other’s metabolism.

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant

during therapy.

Precautions for Nursing Mothers

Communicate with the patient and pediatric healthcare provider regarding the infant’s exposure to

bupropion through human milk. Instruct patients to immediately contact the infant’s healthcare provider if

they note any side effect in the infant that concerns them or is persistent.

Administration Information

Instruct patients to swallow bupropion hydrochloride extended-release tablets (XL) whole so that the

release rate is not altered. Instruct patients if they miss a dose, not to take an extra tablet to make up for

the missed dose and to take the next tablet at the regular time because of the dose-related risk of

seizure. Instruct patients that bupropion hydrochloride extended-release tablets (XL) should be

swallowed whole and not crushed, divided, or chewed. Bupropion hydrochloride extended-release

tablets (XL) should be administered in the morning and may be taken with or without food.

Manufactured by:

Tulex Pharmaceuticals Inc.

Cranbury, NJ 08512 USA

Manufactured for:

Zhejiang Jutai Pharmaceutical Co., Ltd.

No. 51 Donggang Road, Kecheng District,

Quzhou City, Zhejiang Province,

China 324022

All product/brand names are the trademarks of their respective owners.

PI0010000203 Rev. 08/2019

MEDICATION GUIDE

Bupropion Hydrochloride (bue proe' pee on hye'' droe klor' ide) Extended-Release Tablets (XL)

IMPORTANT: Be sure to read the three sections of this Medication Guide. The first section is

about the risk of suicidal thoughts and actions with antidepressant medicines; the second section

is about the risk of changes in thinking and behavior, depression and suicidal thoughts or actions

with medicines used to quit smoking; and the third section is entitled “What Other Important

Information Should I Know About Bupropion Hydrochloride Extended-Release Tablets (XL)?”

Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal

Thoughts or Actions

This section of the Medication Guide is only about the risk of suicidal thoughts and actions with

antidepressant medicines.

What is the most important information I should know about antidepressant medicines,

depression and other serious mental illnesses, and suicidal thoughts or actions?

1. Antidepressant medicines may increase the risk of suicidal thoughts or actions in some

children, teenagers, or young adults within the first few months of treatment.

2. Depression or other serious mental illnesses are the most important causes of suicidal

thoughts and actions. Some people may have a particularly high risk of having suicidal

thoughts or actions. These include people who have (or have a family history of) bipolar illness

(also called manic-depressive illness) or suicidal thoughts or actions.

3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family

member?

Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or

feelings. This is very important when an antidepressant medicine is started or when the dose is

changed.

Call your healthcare provider right away to report new or sudden changes in mood, behavior,

thoughts, or feelings.

Keep all follow up visits with your healthcare provider as scheduled. Call the healthcare

provider between visits as needed, especially if you have concerns about symptoms.

Call your healthcare provider right away if you or your family member has any of the following

symptoms, especially if they are new, worse, or worry you:

thoughts about suicide or dying

attempts to commit suicide

new or worse depression

new or worse anxiety

feeling very agitated or restless

panic attacks

trouble sleeping (insomnia)

new or worse irritability

acting aggressive, being angry, or violent

acting on dangerous impulses

an extreme increase in activity and talking (mania)

other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping

an antidepressant medicine suddenly can cause other symptoms.

Antidepressants are medicines used to treat depression and other illnesses. It is important to

discuss all the risks of treating depression and also the risks of not treating it. Patients and their

families or other caregivers should discuss all treatment choices with the healthcare provider, not

just the use of antidepressants.

Antidepressant medicines have other side effects. Talk to the healthcare provider about the side

effects of the medicine prescribed for you or your family member.

Antidepressant medicines can interact with other medicines. Know all of the medicines that you

or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not

start new medicines without first checking with your healthcare provider.

It is not known if bupropion hydrochloride extended-release tablets (XL) are safe and effective in

children under the age of 18.

Quitting Smoking, Quit-Smoking Medications, Changes in Thinking and Behavior, Depression,

and Suicidal Thoughts or Actions

This section of the Medication Guide is only about the risk of changes in thinking and behavior,

depression and suicidal thoughts or actions with drugs used to quit smoking. Although bupropion

hydrochloride extended-release tablets (XL) are not a treatment for quitting smoking, they contain the

same active ingredient (bupropion hydrochloride) as ZYBAN

which is used to help patients quit

smoking.

Talk to your healthcare provider or your family member’s healthcare provider about:

all risks and benefits of quit-smoking medicines.

all treatment choices for quitting smoking.

When you try to quit smoking, with or without bupropion you may have symptoms that may be due to

nicotine withdrawal, including:

urge to smoke

depressed mood

trouble sleeping

irritability

frustration

anger

feeling anxious

difficulty concentrating

restlessness

decreased heart rate

increased appetite

weight gain

Some people have even experienced suicidal thoughts when trying to quit smoking without medication.

Sometimes quitting smoking can lead to worsening of mental health problems that you already have,

such as depression.

Some people have had serious side effects while taking bupropion to help them quit smoking, including:

New or worse mental health problems, such as changes in behavior or thinking, aggression,

hostility, agitation, depression, or suicidal thoughts or actions. Some people had these symptoms

when they began taking bupropion, and others developed them after several weeks of treatment, or after

stopping bupropion. These symptoms happened more often in people who had a history of mental health

problems before taking bupropion than in people without a history of mental health problems.

Stop taking bupropion hydrochloride extended-release tablets (XL) and call your healthcare

provider right away if you, your family, or caregiver notice any of these symptoms. Work with

your healthcare provider to decide whether you should continue to take bupropion hydrochloride

extended-release tablets (XL). In many people, these symptoms went away after stopping bupropion

hydrochloride extended-release tablets (XL), but in some people symptoms continued after stopping

bupropion hydrochloride extended-release tablets (XL). It is important for you to follow-up with your

healthcare provider until your symptoms go away. Before taking bupropion hydrochloride extended-

release tablets (XL), tell your healthcare provider if you have ever had depression or other mental

health problems. You should also tell your healthcare provider about any symptoms you had during

other times you tried to quit smoking, with or without bupropion.

What Other Important Information Should I Know About Bupropion Hydrochloride Extended-

Release Tablets (XL)?

Seizures: There is a chance of having a seizure (convulsion, fit) with bupropion hydrochloride

extended-release tablets (XL), especially in people:

with certain medical problems.

who take certain medicines.

The chance of having seizures increases with higher doses of bupropion hydrochloride extended-

release tablets (XL). For more information, see the sections “Who should not take bupropion

hydrochloride extended-release tablets (XL)?” and “What should I tell my healthcare provider before

taking bupropion hydrochloride extended-release tablets (XL)?” Tell your healthcare provider about all

of your medical conditions and all the medicines you take. Do not take any other medicines while you

are taking bupropion hydrochloride extended-release tablets (XL) unless your healthcare

provider has said it is okay to take them.

If you have a seizure while taking bupropion hydrochloride extended-release tablets (XL), stop

taking the tablets and call your healthcare provider right away. Do not take bupropion

hydrochloride extended-release tablets (XL) again if you have a seizure.

High blood pressure (hypertension). Some people get high blood pressure that can be severe,

while taking bupropion hydrochloride extended-release tablets (XL). The chance of high blood

pressure may be higher if you also use nicotine replacement therapy (such as a nicotine patch) to

help you stop smoking (see the section of this Medication Guide called “How should I take

bupropion hydrochloride extended-release tablets (XL)?”).

Manic episodes. Some people may have periods of mania while taking bupropion hydrochloride

extended-release tablets (XL) including:

Greatly increased energy

Severe trouble sleeping

Racing thoughts

Reckless behavior

Unusually grand ideas

Excessive happiness or irritability

Talking more or faster than usual

If you have any of the above symptoms of mania, call your healthcare provider.

Unusual thoughts or behaviors. Some patients have unusual thoughts or behaviors while taking

bupropion hydrochloride extended-release tablets (XL), including delusions (believe you are

someone else), hallucinations (seeing or hearing things that are not there), paranoia (feeling that

people are against you), or feeling confused. If this happens to you, call your healthcare provider.

Visual problems.

eye pain

changes in vision

swelling or redness in or around the eye.

Only some people are at risk for these problems. You may want to undergo an eye examination to see if

you are at risk and receive preventative treatment if you are.

Severe allergic reactions. Some people can have severe allergic reactions to bupropion

hydrochloride extended-release tablets (XL). Stop taking bupropion hydrochloride extended-

release tablets (XL) and call your healthcare provider right away if you get a rash, itching,

hives, fever, swollen lymph glands, painful sores in the mouth or around the eyes, swelling of the

lips or tongue, chest pain, or have trouble breathing. These could be signs of a serious allergic

reaction.

What are bupropion hydrochloride extended-release tablets (XL)?

Bupropion hydrochloride extended-release tablets (XL) should be used with a patient support program.

It is important to participate in the behavioral program, counseling, or other support program your

healthcare professional recommends.

Quitting smoking can lower your chances of having lung disease, heart disease, or getting certain types

of cancer that are related to smoking.

Who should not take bupropion hydrochloride extended-release tablets (XL)?

Do not take bupropion hydrochloride extended-release tablets (XL) if you:

have or had a seizure disorder or epilepsy.

have or had an eating disorder such as anorexia nervosa or bulimia.

are taking any other medicines that contain bupropion, including WELLBUTRIN

,

WELLBUTRIN

SR, APLENZIN

, ZYBAN

, or FORFIVO XL

. Bupropion is the same

active ingredient that is in bupropion hydrochloride extended-release tablets (XL).

drink a lot of alcohol and abruptly stop drinking, take medicines called sedatives (these make you

sleepy) or benzodiazepines, or anti-seizure medicines, and you stop taking them all of a sudden.

take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are

not sure if you take an MAOI, including the antibiotic linezolid.

do not take an MAOI within 2 weeks of stopping bupropion hydrochloride extended-

release tablets (XL) unless directed to do so by your healthcare provider.

do not start bupropion hydrochloride extended-release tablets (XL) if you stopped taking

an MAOI in the last 2 weeks unless directed to do so by your healthcare provider.

are allergic to the active ingredient in bupropion hydrochloride extended-release tablets (XL),

bupropion, or to any of the inactive ingredients. See the end of this Medication Guide for a complete

list of ingredients in bupropion hydrochloride extended-release tablets (XL).

What should I tell my healthcare provider before taking bupropion hydrochloride extended-

release tablets (XL)?

Tell your healthcare provider if you have ever had depression, suicidal thoughts or actions, or other

mental health problems. You should also tell your healthcare provider about any symptoms you had

during other times you tried to quit smoking, with or without bupropion hydrochloride extended-release

tablets (XL). See “Quitting Smoking, Quit-Smoking Medications, Changes in Thinking and Behavior,

Depression, and Suicidal Thoughts or Actions.”

®

®

®

®

®

Tell your healthcare provider about your other medical conditions, including if you:

have liver problems, especially cirrhosis of the liver.

have kidney problems.

have, or have had, an eating disorder such as anorexia nervosa or bulimia.

have had a head injury.

have had a seizure (convulsion, fit).

have a tumor in your nervous system (brain or spine).

have had a heart attack, heart problems, or high blood pressure.

are a diabetic taking insulin or other medicines to control your blood sugar.

drink alcohol.

abuse prescription medicines or street drugs.

are pregnant or plan to become pregnant.

are breastfeeding. Bupropion hydrochloride passes into your milk in small amounts.

Tell your healthcare provider about all the medicines you take, including prescription, over-the-

counter medicines, vitamins, and herbal supplements. Many medicines increase your chances of having

seizures or other serious side effects if you take them while you are taking bupropion hydrochloride

extended-release tablets (XL).

How should I take bupropion hydrochloride extended-release tablets (XL)?

Start bupropion hydrochloride extended-release tablets (XL) before you stop smoking to give

bupropion hydrochloride extended-release tablets (XL) time to build up in your body. It takes about

1 week for bupropion hydrochloride extended-release tablets (XL) to start working.

Pick a date to stop smoking that is during the second week you are taking bupropion hydrochloride

extended-release tablets (XL).

Take bupropion hydrochloride extended-release tablets (XL) exactly as prescribed by your

healthcare provider. Do not change your dose or stop taking bupropion hydrochloride extended-

release tablets (XL) without talking with your healthcare provider first.

Bupropion hydrochloride extended-release tablets (XL) are usually taken for 7 to 12 weeks. Your

healthcare provider may decide to prescribe bupropion hydrochloride extended-release tablets

(XL) for longer than 12 weeks to help you stop smoking. Follow your healthcare provider’s

instructions.

Swallow bupropion hydrochloride extended-release tablets (XL) whole. Do not chew, cut, or

crush bupropion hydrochloride extended-release tablets (XL). If you do, the medicine will be

released into your body too quickly. If this happens you may be more likely to get side effects

including seizures. Tell your healthcare provider if you cannot swallow tablets.

Bupropion hydrochloride extended-release tablets (XL) may have an odor. This is normal.

Take your doses of bupropion hydrochloride extended-release tablets (XL) at least 8 hours apart.

You may take bupropion hydrochloride extended-release tablets (XL) with or without food.

It is not dangerous to smoke and take bupropion hydrochloride extended-release tablets (XL) at the

same time. But, you will lower your chance of breaking your smoking habit if you smoke after the

date you set to stop smoking.

You may use bupropion hydrochloride extended-release tablets (XL) and nicotine patches (a type of

nicotine replacement therapy) at the same time, following the precautions below.

You should only use bupropion hydrochloride extended-release tablets (XL) and nicotine

patches together under the care of your healthcare provider. Using bupropion hydrochloride

extended-release tablets (XL) and nicotine patches together may raise your blood pressure, and

sometimes this can be severe.

Tell your healthcare provider if you plan to use nicotine patches. Your healthcare provider

should check your blood pressure regularly if you use nicotine patches with bupropion

hydrochloride extended-release tablets (XL) to help you quit smoking.

If you miss a dose, do not take an extra dose to make up for the dose you missed. Wait and take your

next dose at the regular time. This is very important. Too much bupropion hydrochloride

extended-release tablets (XL) can increase your chance of having a seizure.

If you take too much bupropion hydrochloride extended-release tablets (XL), or overdose, call your

local emergency room or poison control center right away.

Do not take any other medicines while taking bupropion hydrochloride extended-release tablets

(XL) unless your healthcare provider has told you it is okay.

What should I avoid while taking bupropion hydrochloride extended-release tablets (XL)?

Limit or avoid using alcohol during treatment with bupropion hydrochloride extended-release

tablets (XL). If you usually drink a lot of alcohol, talk with your healthcare provider before

suddenly stopping. If you suddenly stop drinking alcohol, you may increase your chance of having

seizures.

Do not drive a car or use heavy machinery until you know how bupropion hydrochloride extended-

release tablets (XL) affects you. bupropion hydrochloride extended-release tablets (XL) can affect

your ability to do these things safely.

What are possible side effects of bupropion hydrochloride extended-release tablets (XL)?

Bupropion hydrochloride extended-release tablets (XL) can cause serious side effects. See the

sections at the beginning of this Medication Guide for information about serious side effects of

bupropion hydrochloride extended-release tablets (XL).

The most common side effects of bupropion hydrochloride extended-release tablets (XL) include:

trouble

sleeping

feeling

anxious

stuffy nose

nausea

dry mouth

constipation

dizziness

joint aches

If you have trouble sleeping, do not take bupropion hydrochloride extended-release tablets (XL) too

close to bedtime.

Tell your healthcare provider right away about any side effects that bother you.

These are not all the possible side effects of bupropion hydrochloride extended-release tablets (XL).

For more information, ask your healthcare provider or pharmacist.

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 Tulex Pharmaceuticals Inc. at 1-609-619-3098.

How should I store bupropion hydrochloride extended-release tablets (XL)?

Store bupropion hydrochloride extended-release tablets at room temperature between 59° and 86°F

(15° to 30°C). Protect from light.

Keep bupropion hydrochloride extended-release tablets (XL) and all medicines out of the reach

of children.

General information about the safe and effective use of bupropion hydrochloride extended-

release tablets (XL).

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

use bupropion hydrochloride extended-release tablets (XL) for a condition for which it was not

prescribed. Do not give bupropion hydrochloride extended-release tablets (XL) to other people, even

if they have the same symptoms you have. It may harm them.

If you take a urine drug screening test, bupropion hydrochloride extended-release tablets (XL) may

make the test result positive for amphetamines. If you tell the person giving you the drug screening test

that you are taking bupropion hydrochloride extended-release tablets (XL), they can do a more specific

drug screening test that should not have this problem.

This Medication Guide summarizes important information about bupropion hydrochloride extended-

release tablets (XL). If you would like more information, talk with your healthcare provider. You can

ask your healthcare provider or pharmacist for information about bupropion hydrochloride extended-

release tablets (XL) that is written for health professionals.

For more information about bupropion hydrochloride extended-release tablets (XL), call Tulex

Pharmaceuticals Inc. at 1 609-619-3098.

What are the ingredients in bupropion hydrochloride extended-release tablets (XL)?

Active ingredient: bupropion hydrochloride.

Inactive ingredients:alcohol, ethylcellulose, hydrochloric acid, hydroxypropyl cellulose,

hypromellose, methacrylic acid and ethyl acrylate copolymer, polyethylene glycol, povidone, purified

water, silicon dioxide, stearic acid and talc. The tablets are printed with edible black ink, which contains

ferrosoferric oxide, hypromellose, propylene glycol, and purified water.

Manufactured by:

Tulex Pharmaceuticals Inc.

Cranbury, NJ 08512 USA

Manufactured for:

Zhejiang Jutai Pharmaceuticals Co., Ltd.

No. 51 Donggang Road, Keecheng District,

Quzhou City, Zhejiang Province, China 324022

All product/brand names are the trademarks of their respective owners.

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

PI0010000203 Rev: 08/2019

PRINCIPAL DISPLAY PANEL - 300 mg Tablet Bottle Label

NDC 71765- 002-03

Rx Only

Once-Daily

buPROPion Hydrochloride

Extended-Release Tablets, (XL)

300mg

Warning: Do not use in combination with Zyban® or with any other medicine that contains

bupropion hydrochloride.

Pharmacists: Dispense the Medication Guide provided separately to each patient.

30 Tablets

Zhejiang Jutai Pharmaceuticals Co., Ltd

LA0020300202 05/2019

Lot:

Exp:

NDC 71765- 002-09

Rx Only

Once-Daily

buPROPion Hydrochloride

Extended-Release Tablets, (XL)

300mg

Warning: Do not use in combination with Zyban® or with any other medicine that contains

bupropion hydrochloride.

Pharmacists: Dispense the Medication Guide provided separately to each patient.

90 Tablets

Zhejiang Jutai Pharmaceuticals Co., Ltd

LA0020900202 05/2019

Lot:

Exp:

NDC 71765- 002-50

Rx Only

Once-Daily

buPROPion Hydrochloride

Extended-Release Tablets, (XL)

300mg

Warning: Do not use in combination with Zyban® or with any other medicine that contains

bupropion hydrochloride.

Pharmacists: Dispense the Medication Guide provided separately to each patient.

500 Tablets

Zhejiang Jutai Pharmaceuticals Co., Ltd

LA0025000202 05/2019

Lot:

Exp:

BUPROPION HYDROCHLORIDE XL

bupropion hydrochloride tablet, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:7176 5-0 0 2

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

Zhejiang Jutai Pharamceutical Co., Ltd

Ingredient Name

Basis of Strength

Stre ng th

BUPRO PIO N HYDRO CHLO RIDE (UNII: ZG7E5POY8 O) (BUPROPION -

UNII:0 1ZG3TPX31)

BUPROPION

HYDROCHLORIDE

30 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

ALCO HO L (UNII: 3K9 9 58 V9 0 M)

ETHYLCELLULO SE, UNSPECIFIED (UNII: 7Z8 S9 VYZ4B)

HYDRO CHLO RIC ACID (UNII: QTT1758 2CB)

HYDRO XYPRO PYL CELLULO SE, UNSPECIFIED (UNII: 9 XZ8 H6 N6 OH)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

METHACRYLIC ACID - ETHYL ACRYLATE CO PO LYMER ( 1:1) TYPE A (UNII: NX76 LV5T8 J)

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

PO VIDO NE, UNSPECIFIED (UNII: FZ9 8 9 GH9 4E)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

STEARIC ACID (UNII: 4ELV7Z6 5AP)

TALC (UNII: 7SEV7J4R1U)

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

PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)

WATER (UNII: 0 59 QF0 KO0 R)

Product Characteristics

Color

white (white to o ff white)

S core

no sco re

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

T0 11

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:7176 5-0 0 2-0 3

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

0 9 /0 6 /20 19

2

NDC:7176 5-0 0 2-0 9

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 9 /0 6 /20 19

3

NDC:7176 5-0 0 2-50

50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 9 /0 6 /20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA21120 0

0 9 /0 6 /20 19

Labeler -

Zhejiang Jutai Pharamceutical Co., Ltd (679884531)

Revised: 9/2019

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