bupropion Hydrochloride

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

BOXED WARNING SECTION

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

9 DRUG ABUSE AND DEPENDENCE

DRUG ABUSE AND DEPENDENCE SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

11 DESCRIPTION

DESCRIPTION SECTION

Bupropion hydrochloride tablets, USP, an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. Its structure closely resembles that of diethylpropion; it is related to phenylethylamines. It is designated as (±)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride. The molecular weight is 276.2. The molecular formula is C 13 H 18 ClNO•HCl. 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: Each bupropion hydrochloride tablet intended for oral administration contains 75 mg or 100 mg bupropion hydrochloride. Each tablet also contains the following inactive ingredients: 75 mg tablet – D&C Yellow No. 10 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake, hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, polyethylene glycol, polysorbate, potassium chloride, pregelatinized starch, stearic acid, titanium dioxide and triacetin; 100 mg tablet – FD&C Red No. 40 Aluminum Lake, hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, polyethylene glycol, polysorbate, potassium chloride, pregelatinized starch, stearic acid, titanium dioxide and triacetin.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

The efficacy of bupropion hydrochloride tablets in the treatment of major depressive disorder was established in two 4‑week, placebo‑controlled trials in adult inpatients with MDD (Trials 1 and 2 in Table 4) and in one 6‑week, placebo‑controlled trial in adult outpatients with MDD (Trial 3 in Table 4). In the first trial, the dose range of bupropion hydrochloride tablets was 300 mg to 600 mg/day administered in 3 divided doses; 78% of subjects were treated with doses of 300 mg to 450 mg/day. The trial demonstrated the efficacy of bupropion hydrochloride tablets as measured by the Hamilton Depression Rating Scale (HDRS) total score, the HDRS depressed mood item (Item 1), and the Clinical Global Impressions-severity score (CGI-S). The second trial included 2 doses of bupropion hydrochloride tablets (300 and 450 mg/day) and placebo. This trial demonstrated the effectiveness of bupropion hydrochloride tablets for only the 450‑mg/day dose. The efficacy results were statistically significant for the HDRS total score and the CGI-S score, but not for HDRS Item 1. In the third trial, outpatients were treated with 300 mg/day of bupropion hydrochloride tablets. This trial demonstrated the efficacy of bupropion hydrochloride tablets as measured by the HDRS total score, the HDRS Item 1, the Montgomery‑Asberg Depression Rating Scale (MADRS), the CGI-S score, and the CGI-Improvement Scale (CGI-I) score. Effectiveness of bupropion hydrochloride tablets in long‑term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials. Table 4. Efficacy of Bupropion Hydrochloride Tablets for the Treatment of Major Depressive Disorder Trial Number Treatment Group Primary Efficacy Measure: HDRS Mean Baseline Score (SD) LS Mean Score at Endpoint Visit (SE) Placebo-subtracted Difference a (95% CI) Trial 1 Bupropion hydrochloride tablets 300-600 mg/day b (n = 48) 28.5 (5.1) 14.9 (1.3) -4.7 (-8.8, -0.6) Placebo (n = 27) 29.3 (7.0) 19.6 (1.6) -- Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Difference a (95% CI) Trial 2 Bupropion hydrochloride tablets 300 mg/day (n = 36) 32.4 (5.9) -15.5 (1.7) -4.1 Bupropion hydrochloride tablets 450 mg/day b (n = 34) 34.8 (4.6) -17.4 (1.7) -5.9 (-10.5, -1.4) Placebo (n = 39) 32.9 (5.4) -11.5 (1.6) -- Trial 3 Bupropion hydrochloride tablets 300 mg/day b (n = 110) 26.5 (4.3) -12.0 (NA) -3.9 (-5.7, -1.0) Placebo (n = 106) 27.0 (3.5) -8.7 (NA) -- n: sample size; SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval included for doses that were demonstrated to be effective; NA: not available. a Difference (drug minus placebo) in least-squares estimates with respect to the primary efficacy parameter. For Trial 1, it refers to the mean score at the endpoint visit; for Trials 2 and 3, it refers to the mean change from baseline to the endpoint visit. b Doses that are demonstrated to be statistically significantly superior to placebo.

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Bupropion Hydrochloride Tablets USP, 75 mg are available as round, yellow colored tablets, debossed " 191 " on one side and plain on other side. They are supplied as follows: Bottles of 100: NDC 23155-191-01 Bottles of 1000: NDC 23155-191-10 Bupropion Hydrochloride Tablets USP, 100 mg are available as round, red colored tablets, debossed " 192 " on one side and plain on other side. They are supplied as follows: Bottles of 100: NDC 23155-192-01 Bottles of 1000: NDC 23155-192-10 The tablets should be protected from light and moisture and stored at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Keep container tightly closed. Protect from light and moisture.

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

Advise the patient to read the FDA-approved patient labeling (Medication Guide). 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 healthcare 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 tablets 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 and contact a healthcare professional if they experience such symptoms [see Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6.2 )]. Severe Allergic Reactions Educate patients on the symptoms of hypersensitivity and to discontinue bupropion hydrochloride tablets if they have a severe allergic reaction. Seizure Instruct patients to discontinue and not restart bupropion hydrochloride tablets if they experience a seizure while on treatment. Advise patients that the excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizure. Advise patients to minimize or avoid use of alcohol. Angle-Closure Glaucoma Patients should be advised that taking bupropion hydrochloride tablets 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 tablets contains the same active ingredient (bupropion hydrochloride) found in ZYBAN®, which is used as an aid to smoking cessation treatment, and that bupropion hydrochloride tablets should not be used in combination with ZYBAN® or any other medications that contain bupropion (such as WELLBUTRIN SR®, the sustained-release formulation and WELLBUTRIN XL® or FORFIVO XL®, the extended-release formulations, and APLENZIN®, the extended-release formulation of bupropion hydrobromide). 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 tablets 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 tablets do not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. Bupropion hydrochloride tablets 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 tablets and other drugs may affect each others’ metabolisms. Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy with bupropion hydrochloride tablets. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to bupropion hydrochloride tablets during pregnancy [see Use in Specific Populations (8.1)]. Storage Information Instruct patients to store bupropion hydrochloride tablets at room temperature, between 68°F and 77°F (20°C to 25°C) and keep the tablets dry and out of the light. Administration Information Instruct patients to take bupropion hydrochloride tablets in equally divided doses 3 or 4 times a day, with doses separated by at least 6 hours to minimize the risk of seizure. 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 tablets should be swallowed whole and not crushed, divided, or chewed. Bupropion hydrochloride tablets can be taken with or without food. Brands listed are the trademarks of their respective owners and are not of Avet Pharmaceuticals Inc. Dispense with Medication Guide available at: www.avetpharma.com/product. Distributed by: Avet Pharmaceuticals Inc. East Brunswick, NJ 08816 1.866.901.DRUG (3784) Revised: 02/2024

MEDICATION GUIDE

SPL MEDGUIDE SECTION

Dispense with Medication Guide available at: www.avetpharma.com/product MEDICATION GUIDE Bupropion Hydrochloride Tablets, USP (bue-PROE-pee-on HYE-droe-KLOR-ide) 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 Tablets?” 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 tablets 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 tablets are not a treatment for quitting smoking, it contains 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 tablets 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 tablets. In many people, these symptoms went away after stopping bupropion hydrochloride tablets, but in some people symptoms continued after stopping bupropion hydrochloride tablets. It is important for you to follow-up with your healthcare provider until your symptoms go away. Before taking bupropion hydrochloride tablets , 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 Tablets? Seizures: There is a chance of having a seizure (convulsion, fit) with bupropion hydrochloride tablets, especially in people: with certain medical problems. who take certain medicines The chance of having seizures increases with higher doses of bupropion hydrochloride tablets. For more information, see the sections “Who should not take bupropion hydrochloride tablets?” and “What should I tell my healthcare provider before taking bupropion hydrochloride tablets?” 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 tablets unless your healthcare provider has said it is okay to take them. If you have a seizure while taking bupropion hydrochloride tablets, stop taking the tablets and call your healthcare provider right away. Do not take bupropion hydrochloride tablets again if you have a seizure. High blood pressure (hypertension). Some people get high blood pressure that can be severe, while taking bupropion hydrochloride tablets. 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 tablets?”). Manic episodes. Some people may have periods of mania while taking bupropion hydrochloride tablets, including: Greatly increased energy Severe trouble sleeping Racing thoughts Reckless behavior Unusually grand ideas Excessive happiness or irritability Talki...

Repackaging Information

SPL UNCLASSIFIED SECTION

Please reference the How Supplied section listed above for a description of individual tablets. This drug product has been received by Aphena Pharma - TN in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are listed below: Count 75 mg 60 71610-866-53 90 71610-866-60 120 71610-866-70 180 71610-866-80 Store between 20°-25°C (68°-77°F). See USP Controlled Room Temperature. Dispense in a tight light-resistant container as defined by USP. Keep this and all drugs out of the reach of children. Repackaged by: Cookeville, TN 38506 20241203AMH

PRINCIPAL DISPLAY PANEL - 75 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 71610-866 - Bupropion Hydrochloride, USP 75 mg Tablets - Rx Only