bupropion
bupropion hydrochloride · Tablet, Extended Release · Oral
Uses
Bupropion hydrochloride extended-release tablets (XL) are an aminoketone antidepressant, indicated for: treatment of major depressive disorder (MDD) ( 1.1 ) prevention of seasonal affective disorder (SAD) ( 1.2 ) 1.1 Major Depressive Disorder (MDD) 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 (SAD) 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 )] .
Dosage and administration
General 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 Impairmen t 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 ) 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 hydrochloride 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 Bupropion Hydrochloride Tablets or from Bupropion Hydrochloride Sustained-Release Tablets When switching patients from bupropion hydrochloride tablets to bupropion hydrochloride extended-release tablets (XL) or from bupropion hydrochloride sustained-release tablets 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 (XL) 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.
Dosage forms and strengths
Extended-release tablets: 150 mg, 300 mg ( 3 ) Bupropion hydrochloride extended-release tablets USP (XL), 150 mg are creamy-white to pale-yellow, round, biconvex, beveled-edge coated-tablets imprinted with '353' in black ink on one side and plain on other side. Bupropion Hydrochloride Extended-release Tablets USP (XL), 300 mg are creamy-white to pale-yellow, round, biconvex, coated-tablets imprinted with '354' in black ink on one side and plain on other side.
Contraindications
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 (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 ) Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients with seizure disorder. Bupropion hydrochloride extended-release tablets (XL) is 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 )].
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 tablets (XL) 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 ) 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 to 24 years 5 additional cases Decreases Compared to Placebo Decreases Compared to Placebo 25 to 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.
Side effects
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 Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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 hydrochloride 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 hydrochloride sustained-release: anorexia, dry mouth, rash, sweating, tinnitus, and tremor. 400 mg/day of bupropion hydrochloride 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 hydrochloride Immediate-Release, Bupropion hydrochloride Sustained-Release, and Bupropion hydrochloride Extended-Release in Major Depressive Disorder Trials In placebo-controlled clinical trials with bupropion hydrochloride 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 Hydrochloride Sustained-Release 300 mg/day (n=376) Bupropion Hydrochloride Sustained-Release 400 mg/day (n=114) Rash 0% 2.4% 0.9% Nausea 0.3% 0.8% 1.8% Agitation 0.3% 0.3% 1.8% Migraine 0.3% 0% 1.8% In clinical trials with bupropion hydrochloride 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 hydrochloride Immediate-Release or Bupropion hydrochloride Sustained-Release in MDD Table 3 summarizes the adverse reactions that occurred in placebo-controlled trials in patients treated with bupropion hydrochloride 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 * Incidence based on the number of female patients.
Drug interactions
7 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 ) 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.
Use in specific populations
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/. Risk Summary Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall (see Data). There are risks to the mother associated with untreated depression (see Clinical Considerations). When bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times the maximum recommended human dose (MRHD) of 450 mg/day. When given to pregnant rabbits during organogenesis, non-dose-related increases in incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the MRHD and greater. Decreased fetal weights were seen at doses twice the MRHD and greater (see Animal Data) . The estimated background risk for major birth defects and miscarriage are unknown for the indicated population. All pregnancies have a background rate of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum. Data Human Data Data from the 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. The Registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations. 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, which has a limited number of exposed cases with cardiovascular malformations, 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 odds ratio (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 pregnant rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively (approximately 10 and 6 times the MRHD, respectively, on a mg/m 2 basis). There was no evidence of fetal malformations in rats. When given to pregnant rabbits during organogenesis, nondose-related increases in incidence 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 2 basis) and greater. Decreased fetal weights were observed at doses of 50 mg/kg/day (approximately 2 times the MRHD on a mg/m 2 basis) and greater. No maternal toxicity was evident at doses of 50 mg/kg/day or less. In a pre-and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day (approximately 3 times the MRHD on a mg/m 2 basis) from embryonic implantation through lactation had no effect on pup growth or development.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/. Risk Summary Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall (see Data). There are risks to the mother associated with untreated depression (see Clinical Considerations). When bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times the maximum recommended human dose (MRHD) of 450 mg/day. When given to pregnant rabbits during organogenesis, non-dose-related increases in incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the MRHD and greater. Decreased fetal weights were seen at doses twice the MRHD and greater (see Animal Data) . The estimated background risk for major birth defects and miscarriage are unknown for the indicated population. All pregnancies have a background rate of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum. Data Human Data Data from the 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. The Registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations. 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, which has a limited number of exposed cases with cardiovascular malformations, 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 odds ratio (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 pregnant rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively (approximately 10 and 6 times the MRHD, respectively, on a mg/m 2 basis). There was no evidence of fetal malformations in rats. When given to pregnant rabbits during organogenesis, nondose-related increases in incidence 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 2 basis) and greater. Decreased fetal weights were observed at doses of 50 mg/kg/day (approximately 2 times the MRHD on a mg/m 2 basis) and greater. No maternal toxicity was evident at doses of 50 mg/kg/day or less. In a pre-and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day (approximately 3 times the MRHD on a mg/m 2 basis) from embryonic implantation through lactation had no effect on pup growth or development.
Pediatric use
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 )] .
Geriatric use
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 ) ] .
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, mental status changes, sinus tachycardia, ECG changes such as conduction disturbances or arrhythmias, clonus, myoclonus and hyperreflexia. 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. 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.
Description
Bupropion hydrochloride extended-release tablets, USP (XL) is 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 13 H 18 ClNO
• HCl. Bupropion hydrochloride, USP powder is white, crystalline, and highly soluble in water, in 0.1 N hydrochloric acid, and in alcohol. It has a bitter taste and produces the sensation of local anesthesia on the oral mucosa. The structural formula is: Each bupropion hydrochloride extended-release tablets, USP (XL) intended for oral administration contains 150 mg or 300 mg of bupropion hydrochloride. In addition, each tablet contains the following inactive ingredients: ethyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer dispersion, polyethylene glycol, povidone, silicon dioxide, triethyl citrate. The tablet is printed with black pharmaceutical ink which contains ammonium hydroxide, butyl alcohol, iron oxide black, isopropyl alcohol, propylene glycol and shellac. The insoluble shell of the extended-release tablet may remain intact during gastrointestinal transit and is eliminated in the feces. The Product meets USP Dissolution Test 26. Bupropion hydrochloride extended-release tablets, USP (XL)
Mechanism of action
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.
How supplied
Bupropion Hydrochloride Extended-release Tablets USP (XL), 150 mg are creamy-white to pale-yellow, round, biconvex, beveled-edge coated-tablets imprinted with '353' in black ink on one side and plain on other side and are supplied as follows: NDC 68382-353-06 in bottle of 30 tablets with child-resistant closure NDC 68382-353-16 in bottle of 90 tablets with child-resistant closure NDC 68382-353-05 in bottle of 500 tablets NDC 68382-353-10 in bottle of 1000 tablets Bupropion Hydrochloride Extended-release Tablets USP (XL), 300 mg are creamy-white to pale-yellow, round, biconvex, coated-tablets imprinted with '354' in black ink on one side and plain on other side and are supplied as follows: NDC 68382-354-06 in bottle of 30 tablets with child-resistant closure NDC 68382-354-16 in bottle of 90 tablets with child-resistant closure NDC 68382-354-05 in bottle of 500 tablets NDC 68382-354-10 in bottle of 1000 tablets Storage Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP. Bupropion Hydrochloride Extended-release Tablets USP (XL) may have an odor.
Patient information
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 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) contains 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 (XL) 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 hydrochloride 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 with bupropion hydrochloride extended-release tablets (XL). Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to bupropion hydrochloride extended-release tablets (XL) during pregnancy [see Use in Specific Populations ( 8.1 )]. 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. Medication Guide available at www.zydususa.com/medguides or call 1-877-993-8779.
Label text from the FDA structured product label by Zydus Pharmaceuticals USA Inc. (revised May 21, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Bupropion Hydrochloride in 8 products
bupropion NDC products (8)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 71335-0801 | Bupropion Hydrochloride 200 mg/1 Tablet, Extended Release | Bryant Ranch Prepack | ANDA |
| 51655-357 | Bupropion Hydrochloride 150 mg/1 Tablet, Film Coated, Extended Release | Northwind Health Company, LLC | ANDA |
| 63187-521 | Bupropion Hydrochloride 300 mg/1 Tablet, Extended Release | Proficient Rx LP | ANDA |
| 71205-565 | Bupropion Hydrochloride 150 mg/1 Tablet, Extended Release | Proficient Rx LP | ANDA |
| 65841-780 | Bupropion Hydrochloride 300 mg/1 Tablet, Extended Release | Zydus Lifesciences Limited | ANDA |
| 65841-836 | Bupropion Hydrochloride 150 mg/1 Tablet, Extended Release | Zydus Lifesciences Limited | ANDA |
| 68382-353 | Bupropion Hydrochloride 150 mg/1 Tablet, Extended Release | Zydus Pharmaceuticals USA Inc. | ANDA |
| 68382-354 | Bupropion Hydrochloride 300 mg/1 Tablet, Extended Release | Zydus Pharmaceuticals USA Inc. | ANDA |
bupropion recalls
- D-0207-2017 Dec 28, 2016 · Class III · Terminated
Failed Dissolution Specifications; 6 month time point - D-0149-2017 Nov 30, 2016 · Class III · Terminated
Failed Dissolution Specifications: Product did not meet dissolution specification at an intermediate time point.
Frequently asked questions
What is bupropion used for?
Bupropion hydrochloride extended-release tablets (XL) are an aminoketone antidepressant, indicated for: treatment of major depressive disorder (MDD) ( 1.1 ) prevention of seasonal affective disorder (SAD) ( 1.2 ) 1.1 Major Depressive Disorder (MDD) Bupropion hydrochloride extended-release tablets (XL) are indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic…
What are the side effects of bupropion?
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 Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch… See the full label for the complete list.
Who makes bupropion?
bupropion is listed by 5 labelers in the FDA NDC directory, including Bryant Ranch Prepack, Northwind Health Company, LLC, Proficient Rx LP, Zydus Lifesciences Limited.
Has bupropion been recalled?
The FDA enforcement database lists 2 recalls for bupropion, most recently D-0207-2017 (class iii): Failed Dissolution Specifications; 6 month time point