Bupropion Hydrochloride SR

Product Type: HUMAN PRESCRIPTION DRUG

Route: ORAL

Dosage Form:

NDC: 50090-1150

Application: ANDA079094

Effective: 20231209

1 INDICATIONS AND USAGE Bupropion hydrochloride extended-release tablets (SR) are indicated as an aid to smoking cessation treatment. Bupropion hydrochloride extended-release tablets (SR) are an aminoketone agent indicated as an aid to smoking cessation treatment. ( 1 )

2 DOSAGE AND ADMINISTRATION Starting dose: 150 mg per day for first 3 days. ( 2.1 ) General: Increase dose gradually to reduce seizure risk. ( 2.1 , 5.3 ) Begin dosing one week before quit day. ( 2.1 ) After 3 days, increase the dose to 300 mg per day, given as 150 mg twice daily at an interval of at least 8 hours. ( 2.1 ) May be used with a nicotine transdermal system. ( 2.5 ) Moderate to severe hepatic impairment: 150 mg every other day. ( 2.6 , 8.7 ) 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. ( 2.7 , 8.6 ) 2.1 Usual Dosage Treatment with bupropion hydrochloride extended-release tablets (SR) should be initiated before the patient’s planned quit day, while the patient is still smoking, because it takes approximately 1 week of treatment to achieve steady-state blood levels of bupropion. The patient should set a “target quit date” within the first 2 weeks of treatment with bupropion hydrochloride extended-release tablets (SR). Dosing To minimize the risk of seizure: Begin dosing with one 150 mg tablet per day for 3 days. Increase dose to 300 mg per day given as one 150 mg tablet twice each day with an interval of at least 8 hours between each dose. Do not exceed 300 mg per day. Bupropion hydrochloride extended-release tablets (SR) should be swallowed whole and not crushed, divided, or chewed, as this may lead to an increased risk of adverse effects including seizures [see Warnings and Precautions ( 5.3 )] . Bupropion hydrochloride extended-release tablets (SR) may be taken with or without food [see Clinical Pharmacology ( 12.3 )] . 2.2 Duration of Treatment Treatment with bupropion hydrochloride extended-release tablets (SR) should be continued for 7 to 12 weeks. If the patient has not quit smoking after 7 to 12 weeks, it is unlikely that he or she will quit during that attempt so treatment with bupropion hydrochloride extended-release tablets (SR) should probably be discontinued and the treatment plan reassessed. The goal of therapy with bupropion hydrochloride extended-release tablets (SR) is complete abstinence. Discuss discontinuing treatment with bupropion hydrochloride extended-release tablets (SR) after 12 weeks if the patient feels ready but consider whether the patient may benefit from ongoing treatment. Patients who successfully quit after 12 weeks of treatment but do not feel ready to discontinue treatment should be considered for ongoing therapy with bupropion hydrochloride extended-release tablets (SR); longer treatment should be guided by the relative benefits and risks for individual patients. It is important that patients continue to receive counseling and support throughout treatment with bupropion hydrochloride extended-release tablets (SR) and for a period of time thereafter. 2.3 Individualization of Therapy Patients are more likely to quit smoking and remain abstinent if they are seen frequently and receive support from their physicians or other healthcare professionals. It is important to ensure that patients read the instructions provided to them and have their questions answered. Physicians should review the patient’s overall smoking cessation program that includes treatment with bupropion hydrochloride extended-release tablets (SR). Patients should be advised of the importance of participating in the behavioral interventions, counseling, and/or support services to be used in conjunction with bupropion hydrochloride extended-release tablets (SR) [see Medication Guide ] . Patients who fail to quit smoking during an attempt may benefit from interventions to improve their chances for success on subsequent attempts. Patients who are unsuccessful should be evaluated to determine why they failed. A new quit attempt should be encouraged when factors that contributed to failure can be eliminated or reduced, and conditions are more favorable. 2.4 Maintenance Tobacco dependence is a chronic condition. Some patients may need ongoing treatment. Whether to continue treatment with bupropion hydrochloride extended-release tablets (SR) for periods longer than 12 weeks for smoking cessation must be determined for individual patients. 2.5 Combination Treatment with Bupropion Hydrochloride Extended-Release Tablets (SR) and a Nicotine Transdermal System (NTS) Combination treatment with bupropion hydrochloride extended-release tablets (SR) and NTS may be prescribed for smoking cessation. The prescriber should review the complete prescribing information for both bupropion hydrochloride extended-release tablets (SR) and NTS before using combination treatment [see Clinical Studies ( 14 )]. Monitoring for treatment-emergent hypertension in patients treated with the combination of bupropion hydrochloride extended-release tablets (SR) and NTS is recommended. 2.6 Dose Adjustment in Patients with Hepatic Impairment In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose should not exceed 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 ), 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 (SR) in patients with renal impairment (Glomerular Filtration Rate less than 90 mL per min) [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )] . 2.8 Use of Bupropion Hydrochloride Extended-Release Tablets (SR) with Reversible MAOIs Such as Linezolid or Methylene Blue Do not start bupropion hydrochloride extended-release tablets (SR) in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase the risk of hypertensive reactions [see Contraindications ( 4 ), Drug Interactions ( 7.6 )] . In some cases, a patient already receiving therapy with bupropion hydrochloride extended-release tablets (SR) 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 (SR) 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 (SR) 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 (SR) is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use [see Contraindications ( 4 ), Drug Interactions ( 7.6 )] .

4 CONTRAINDICATIONS Bupropion hydrochloride extended-release tablets (SR) are contraindicated in patients with a seizure disorder. Bupropion hydrochloride extended-release tablets (SR) 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 the immediate-release formulation of bupropion [see Warnings and Precautions ( 5.3 )] . Bupropion hydrochloride extended-release tablets (SR) are contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7.3 )] . The use of MAOIs (intended to treat psychiatric disorders) concomitantly with bupropion hydrochloride extended-release tablets (SR) or within 14 days of discontinuing treatment with bupropion hydrochloride extended-release tablets (SR) is contraindicated. There is an increased risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (SR) are used concomitantly with MAOIs. The use of bupropion hydrochloride extended-release tablets (SR) within 14 days of discontinuing treatment with an MAOI is also contraindicated. Starting bupropion hydrochloride extended-release tablets (SR) in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated [see Dosage and Administration ( 2.8 ), Warnings and Precautions ( 5.4 ), Drug Interactions ( 7.6 )] . Bupropion hydrochloride extended-release tablets (SR) are contraindicated in patients with a known hypersensitivity to bupropion or other ingredients of bupropion hydrochloride extended-release tablets (SR). Anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported [see Warnings and Precautions ( 5.8 )] . Seizure disorder. ( 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 (SR) or within 14 days of stopping treatment with bupropion hydrochloride extended-release tablets (SR). Do not use bupropion hydrochloride extended-release tablets (SR) within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start bupropion hydrochloride extended-release tablets (SR) 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 (SR). ( 4 , 5.8 )

Not available.

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Suicidal thoughts and behaviors in adolescents and young adults [see Boxed Warning , W arnings 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 reactions [see Warnings and Precautions ( 5.6 )] Angle-closure glaucoma [see Warnings and Precautions ( 5.7 )] Hypersensitivity reactions [see Warnings and Precautions ( 5.8 )] Most common adverse reactions (incidence greater than or equal to 5% and greater than or equal to 1% more than placebo rate) are insomnia, rhinitis, dry mouth, dizziness, nervous disturbance, anxiety, nausea, constipation, and arthralgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Ad v e r se Reactions Leading to Discontinuation of Treatment Adverse reactions were sufficiently troublesome to cause discontinuation of treatment in 8% of the 706 subjects treated with bupropion hydrochloride extended-release tablets (SR) and 5% of the 313 patients treated with placebo. The more common events leading to discontinuation of treatment with bupropion hydrochloride extended-release tablets (SR) included nervous system disturbances (3.4%), primarily tremors, and skin disorders (2.4%), primarily rashes. Commonly Observed Adverse Reactions The most commonly observed adverse reactions consistently associated with the use of bupropion hydrochloride extended-release tablets (SR) were dry mouth and insomnia. The incidence of dry mouth and insomnia may be related to the dose of bupropion hydrochloride extended-release tablets (SR). The occurrence of these adverse reactions may be minimized by reducing the dose of bupropion hydrochloride extended-release tablets (SR). In addition, insomnia may be minimized by avoiding bedtime doses. Adverse reactions reported in the dose-response and comparator trials are presented in Table 2 and Table 3, respectively. Reported adverse reactions were classified using a COSTART-based dictionary. Table 2. Adverse Reactions Reported by at Least 1% of Subjects and at a Greater Frequency than Placebo in the Dose-Response Trial Adverse Reaction Bupropion Hydrochloride Extended-Release Tablets (SR) 100 to 300 mg/day ( n = 461) % P lacebo ( n = 150) % Body (General) Neck pain 2 <1 Allergic reaction 1 0 Cardiovascular Hot flashes 1 0 Hypertension 1 <1 Digestive Dry mouth 11 5 Increased appetite 2 <1 Anorexia 1 <1 Musculoskeletal Arthralgia 4 3 Myalgia 2 1 Nervous system Insomnia 31 21 Dizziness 8 7 Tremor 2 1 Somnolence 2 1 Thinking abnormality 1 0 Respiratory Bronchitis 2 0 Skin Pruritus 3 <1 Rash 3 <1 Dry skin 2 0 Urticaria 1 0 Special senses Taste perversion 2 <1 Table 3. Adverse Reactions Reported by at Least 1% of Subjects on Active Treatment and at a Greater Frequency than Placebo in the Comparator Trial Adverse Experience (COSTART Term) Bupropion Hydrochloride Extended-Release Tablets (SR) 300 mg/day ( n = 243) % Nicotine Transdermal System (NTS) 21 mg/day (n = 243) % Bupropion Hydrochloride Extended-Release Tablets (SR) and NTS (n = 244) % Placebo (n = 159) % Body Abdominal pain 3 4 1 1 Accidental injury 2 2 1 1 Chest pain <1 1 3 1 Neck pain 2 1 <1 0 Facial edema <1 0 1 0 Cardiovascular Hypertension 1 <1 2 0 Palpitations 2 0 1 0 Digestive Nausea 9 7 11 4 Dry mouth 10 4 9 4 Constipation 8 4 9 3 Diarrhea 4 4 3 1 Anorexia 3 1 5 1 Mouth ulcer 2 1 1 1 Thirst <1 <1 2 0 Musculoskeletal Myalgia 4 3 5 3 Arthralgia 5 3 3 2 Nervous system Insomnia 40 28 45 18 Dream abnormality 5 18 13 3 Anxiety 8 6 9 6 Disturbed concentration 9 3 9 4 Dizziness 10 2 8 6 Nervousness 4 <1 2 2 Tremor 1 <1 2 0 Dysphoria <1 1 2 1 Respiratory Rhinitis 12 11 9 8 Increased cough 3 5 <1 1 Pharyngitis 3 2 3 0 Sinusitis 2 2 2 1 Dyspnea 1 0 2 1 Epistaxis 2 1 1 0 Skin Application site reaction a 11 17 15 7 Rash 4 3 3 2 Pruritus 3 1 5 1 Urticaria 2 0 2 0 Special senses Taste perversion 3 1 3 2 Tinnitus 1 0 <1 0 a Subjects randomized to bupropion hydrochloride extended-release tablets (SR) or placebo received placebo patches. Adverse reactions in a 1-year maintenance trial and a 12-week COPD trial with bupropion hydrochloride extended-release tablets (SR) were quantitatively and qualitatively similar to those observed in the dose-response and comparator trials. In the trial of patients without or with a history of psychiatric disorder, the most common adverse events in subjects treated with bupropion hydrochloride extended-release tablets (SR) were broadly similar to those observed in premarketing studies. Adverse events reported in greater than 10% of subjects treated with bupropion hydrochloride extended-release tablets (SR) in the entire study population were nausea, insomnia, and anxiety disorders. Additionally, the following psychiatric adverse events were reported in greater than 2% of patients in either treatment group (bupropion hydrochloride extended-release tablets (SR) vs. placebo) by cohort. For the non-psychiatric cohort, these adverse events were anxiety, nervousness, abnormal dreams, and insomnia. For the psychiatric cohort, these adverse events were agitation, anxiety, panic, abnormal dreams, insomnia, and crying. Other Adverse Reactions Observed during the Clinical Development of Bupropion In addition to the adverse reactions noted above, the following adverse reactions have been reported in clinical trials with the sustained-release formulation of bupropion in depressed subjects and in nondepressed smokers, as well as in clinical trials with the immediate-release formulation of bupropion. Adverse reaction frequencies represent the proportion of subjects who experienced a treatment-emergent adverse reaction on at least one occasion in placebo-controlled trials for depression (n = 987) or smoking cessation (n = 1,013), or subjects who experienced an adverse reaction requiring discontinuation of treatment in an open-label surveillance trial with bupropion sustained-release tablets (n = 3,100). All treatment-emergent adverse reactions are included except those listed in Tables 2 and 3, those listed in other safety-related sections of the prescribing information, those subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, those not reasonably associated with the use of the drug, and those that were not serious and occurred in fewer than 2 subjects. Adverse reactions are further categorized by body system and listed in order of decreasing frequency according to the following definitions of frequency: Frequent adverse reactions are defined as those occurring in at least 1/100 subjects. Infrequent adverse reactions are those occurring in 1/100 to 1/1,000 subjects, while rare events are those occurring in less than 1/1,000 subjects. Bod y (General): Frequent were asthenia, fever, and headache. Infrequent were chills, inguinal hernia, and photosensitivity. Rare was malaise. Cardiovascular: Infrequent were flushing, migraine, postural hypotension, stroke, tachycardia, and vasodilation. Rare was syncope. Digestive: Frequent were dyspepsia and vomiting. Infrequent were abnormal liver function, bruxism, dysphagia, gastric reflux, gingivitis, jaundice, and stomatitis. Hemic and Lymphatic: Infrequent was ecchymosis. M e tabolic and Nutritional: Infrequent were edema and peripheral edema. M u sculoskeletal: Infrequent were leg cramps and twitching. Nervous System: Frequent were agitation, depression, and irritability. Infrequent were abnormal coordination, CNS stimulation, confusion, decreased libido, decreased memory, depersonalization, emotional lability, hostility, hyperkinesia, hypertonia, hypesthesia, paresthesia, suicidal ideation, and vertigo. Rare were amnesia, ataxia, derealization, and hypomania. Respiratory: Rare was bronchospasm. S kin: Frequent was sweating. Spe cial Senses: Frequent was blurred vision or diplopia. Infrequent were accommodation abnormality and dry eye. Urogenital: Frequent was urinary frequency. Infrequent were impotence, polyuria, and urinary urgency. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of bupropion hydrochloride extended-release tablets (SR) and are not described elsewhere in the label. 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 relationship to drug exposure. Body ( General) Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness [see Warnings and Precautions ( 5.8 )] . Cardiovascular Cardiovascular disorder, complete atrioventricular block (AV) block, extrasystoles, hypotension, myocardial infarction, phlebitis, and pulmonary embolism. Digestive Colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, increased salivation, intestinal perforation, liver damage, pancreatitis, stomach ulcer, and stool abnormality. Endo crine Hyperglycemia, hypoglycemia, hyponatremia, and syndrome of inappropriate antidiuretic hormone secretion. Hemic and Lymphatic Anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia. Altered prothrombin time (PT) and/or international normalized ratio (INR), infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin. M e tabolic and Nutritional Glycosuria. M u sculoskeletal Arthritis and muscle rigidity/fever/rhabdomyolysis, and muscle weakness. Nervous System Abnormal electroencephalogram (EEG), aggression, akinesia, aphasia, coma, completed suicide, delirium, delusions, dysarthria, euphoria, extrapyramidal syndrome (dyskinesia, dystonia, hypokinesia, parkinsonism), hallucinations, increased libido, manic reaction, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking tardive dyskinesia. Respiratory Pneumonia. S kin Alopecia, angioedema, exfoliative dermatitis, hirsutism, and Stevens-Johnson syndrome. Spe cial Senses Deafness, increased intraocular pressure, and mydriasis. Urogenital Abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, menopause, painful erection, prostate disorder, salpingitis, urinary incontinence, urinary retention, urinary tract disorder, and vaginitis.