DailyMed Label: Bupropion Hydrochloride

DailyMed Label: Bupropion Hydrochloride

2022

DailyMed Prescription

Bupropion Hydrochloride

bupropion hydrochloride

Dr. Reddy’s Laboratories Inc.

NDC: 43598-536

NDC: 43598-537

NDC: 43598-538

NDC: 43598-536

NDC: 43598-537

NDC: 43598-538

NDC: 43598-536

NDC: 43598-536

NDC: 43598-537

NDC: 43598-537

NDC: 43598-538

NDC: 43598-538

Bupropion hydrochloride extended-release tablets, USP (SR), 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-[(1,1­dimethylethyl)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, powder, soluble in 0.1N HCl, alcohol 96% and 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, USP (SR), are supplied for oral administration as 100 mg (blue), 150 mg (purple), and 200 mg (pink), film-coated, extended-release tablets. Each tablet contains the labeled amount of bupropion hydrochloride and the inactive ingredients: copovidone, cysteine hydrochloride,hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol,polysorbate 80 and titanium dioxide.In addition, the 100 mg tablet contains FD&C Blue No. 1 Brilliant Blue FCF Aluminium Lake, the 150 mg tablet contains FD&C Blue No. 2 Indigo Carmine Aluminium Lake and FD&C Red No. 40 Allura Red AC Aluminium Lake, and the 200 mg tablet contains FD&C Red No. 40 Allura Red AC Aluminium Lake. Bupropion hydrochloride extended-release tablets, USP (SR) meets USP Dissolution Test 2.

Bupropion hydrochloride extended-release tablets (SR) is indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM). The efficacy of bupropion in the treatment of a major depressive episode was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult subjects with MDD [see Clinical Studies ( 14 )] . The efficacy of bupropion hydrochloride extended-release tablets (SR) in maintaining an antidepressant response for up to 44 weeks following 8 weeks of acute treatment was demonstrated in a placebo-controlled trial [see Clinical Studies ( 14 )] .

Starting dose: 150 mg per day. ( 2.1 ) General: Increase dose gradually to reduce seizure risk. ( 2.1 , 5.3 ) After 3 days, may increase the dose to 300 mg per day, given as 150 mg twice daily at an interval of at least 8 hours. ( 2.1 ) Usual target dose: 300 mg per day as 150 mg twice daily. ( 2.1 ) Maximum dose: 400 mg per day, given as 200 mg twice daily, for patients not responding to 300 mg per day. (2.1) Periodically reassess the dose and need for maintenance treatment. ( 2.1 ) Moderate to severe hepatic impairment: 100 mg daily or 150 mg every other day. ( 2.2 , 8.7 ) Mild hepatic impairment: Consider reducing the dose and/or frequency of dosing. ( 2.2 , 8.7 ) Renal impairment: Consider reducing the dose and/or frequency. ( 2.3 , 8.6 )

100 mg – blue, round, biconvex, film coated tablets, debossed with ‘SG, 174’ on one side and plain on other side. 150 mg – purple, round, biconvex, film coated tablets, debossed with ‘SG, 175’ on one side and plain on other side. 200 mg – pink, round, biconvex, film coated tablets, debossed with ‘SG, 176’ on one side and plain on other side.

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 ( 2.4 , 2.5 ), Warnings and Precautions ( 5.4 ), Drug Interactions ( 7.6 )]. Bupropion hydrochloride extended-release tablets (SR) are contraindicated in patients with 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 )].

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 for the occurrence of such symptoms and instruct them to discontinue bupropion and contact a healthcare provider if they experience such adverse events. ( 5.2 ) Seizure risk: The risk is dose-related. Can minimize risk by gradually increasing the dose and limiting daily dose to 400 mg. Discontinue if seizure occurs. ( 4 , 5.3 , 7.3 ) Hypertension: Bupropion hydrochloride extended-release tablets (SR) 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 )

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

CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based on clinical response, 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 ) Digoxin: May decrease plasma digoxin levels. Monitor digoxin levels. ( 7.2 ) Drugs that lower seizure threshold: Dose bupropion hydrochloride extended-release tablets (SR) with caution. ( 5.3 , 7.3 ) Dopaminergic drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly with bupropion hydrochloride extended-release tablets (SR). ( 7.4 ) MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly with bupropion hydrochloride extended-release tablets (SR). ( 7.6 ) Drug-laboratory test interactions: Bupropion hydrochloride extended-release tablets (SR) can cause false-positive urine test results for amphetamines. ( 7.7 )

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

Bupropion hydrochloride extended-release tablets, USP (SR), 100 mg of bupropion hydrochloride, are blue, round, biconvex, film coated tablets, debossed with ‘SG, 174’ on one side and plain on other side in Bottles of 60 (43598-536-60) Tablets Bottles of 100 (43598-536-01) Tablets Bottles of 500 (43598-536-05) Tablets Bupropion hydrochloride extended-release tablets, USP (SR), 150 mg of bupropion hydrochloride, are purple, round, biconvex, film coated tablets, debossed with ‘SG, 175’ on one side and plain on other side in Bottles of 60 (43598-537-60) Tablets Bottles of 100 (43598-537-01) Tablets Bottles of 500 (43598-537-05) Tablets Bupropion hydrochloride extended-release tablets, USP (SR), 200 mg of bupropion hydrochloride, are pink, round, biconvex, film coated tablets, debossed with ‘SG, 176’ on one side and plain on other side in Bottles of 60 (43598-538-60) Tablets Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container with a child-resistant closure (as required). Protect from light and moisture.

The exact mechanism of the antidepressant action of bupropion is not known, but is presumed to be related to noradrenergic and/or dopaminergic mechanisms. Bupropion is a relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine, and does not inhibit the reuptake of serotonin. Bupropion does not inhibit monoamine oxidase.

Lifetime carcinogenicity studies were performed in rats and mice at bupropion doses up to 300 and 150 mg per kg per day, respectively. These doses are approximately 7 and 2 times the MRHD, respectively, on a mg per m 2 basis. In the rat study there was an increase in nodular proliferative lesions of the liver at doses of 100 to 300 mg per kg per day (approximately 2 to 7 times the MRHD on a mg per m 2 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 the Ames bacterial mutagenicity assay. 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 per kg per day revealed no evidence of impaired fertility.

The efficacy of the immediate-release formulation of bupropion 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 6) and in one 6-week, placebo-controlled trial in adult outpatients with MDD (Trial 3 in Table 6). In the first trial, the dose range of bupropion was 300 mg to 600 mg per day administered in divided doses; 78% of subjects were treated with doses of 300 mg to 450 mg per day. This trial demonstrated the effectiveness of the immediate-release formulation of bupropion 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 the immediate-release formulation of bupropion (300 and 450 mg per day) and placebo. This trial demonstrated the effectiveness of the immediate-release formulation of bupropion, but only at the 450-mg-per-day dose. The efficacy results were 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 per day of the immediate release formulation of bupropion. This trial demonstrated the efficacy of the immediate-release formulation of bupropion 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. Table 6. Efficacy of Immediate-Release Bupropion for the Treatment of Major Depressive Disorder Primary Efficacy Measure: HDRS Trial Number Treatment Group Mean Baseline Score (SD) LS Mean Score at Endpoint Visit (SE) Placebo-subtracted Difference a (95% CI) Trial 1 Immediate-Release Bupropion 300 mg/day to 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 Immediate-Release Bupropion 300 mg/day (n = 36) 32.4 (5.9) -15.5 (1.7) -4.1 Immediate-Release Bupropion 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 Immediate-Release Bupropion 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. Although there are not as yet independent trials demonstrating the antidepressant effectiveness of the sustained‑release formulation of bupropion, trials have demonstrated the bioequivalence of the immediate‑release and sustained‑release forms of bupropion under steady‑state conditions, i.e., bupropion sustained‑release 150 mg twice daily was shown to be bioequivalent to 100 mg 3 times daily of the immediate‑release formulation of bupropion, with regard to both rate and extent of absorption, for parent drug and metabolites. In a longer-term trial, outpatients meeting DSM-IV criteria for major depressive disorder, recurrent type, who had responded during an 8-week open trial on bupropion hydrochloride extended-release tablets (SR) (150 mg twice daily) were randomized to continuation of their same dose of bupropion hydrochloride extended-release tablets (SR) or placebo for up to 44 weeks of observation for relapse. Response during the open phase was defined as CGI Improvement 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 receiving continued treatment with bupropion hydrochloride extended-release tablets (SR) experienced significantly lower relapse rates over the subsequent 44 weeks compared with those receiving placebo.

NDC 43598-536-60 Bupropion HCL Extended-Release Tablets, USP (SR) PHARMACIST: Dispense the accompanying Medication Guide to each patient. 100 mg Rx only 60 Tablets Package/Label Display Panel NDC 43598-536-01 Bupropion HCL Extended-Release Tablets, USP (SR) PHARMACIST: Dispense the accompanying Medication Guide to each patient. 100 mg Rx only 100 Tablets Package/Label Display Panel NDC 43598-536-05 Bupropion HCL Extended-Release Tablets, USP (SR) PHARMACIST: Dispense the accompanying Medication Guide to each patient. 100 mg Rx only 500 Tablets Package/Label Display Panel NDC 43598-537-60 Bupropion HCL Extended-Release Tablets, USP (SR) PHARMACIST: Dispense the accompanying Medication Guide to each patient. 150 mg Rx only 60 Tablets Package/Label Display Panel NDC 43598-537-01 Bupropion HCL Extended-Release Tablets, USP (SR) PHARMACIST: Dispense the accompanying Medication Guide to each patient. 150 mg Rx only 100 Tablets Package/Label Display Panel NDC 43598-537-05 Bupropion HCL Extended-Release Tablets, USP (SR) PHARMACIST: Dispense the accompanying Medication Guide to each patient. 150 mg Rx only 500 Tablets Package/Label Display Panel NDC 43598-538-60 Bupropion HCL Extended-Release Tablets, USP (SR) PHARMACIST: Dispense the accompanying Medication Guide to each patient. 200 mg Rx only 60 Tablets Package/Label Display Panel