Bupropion

Bupropion
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]

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Black Box Warning

Suicidal thoughts and behaviours; and neuropsychiatry reactions See full prescribing information for complete Boxed Warning. *Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. Monitor for worsening and emergence of suicidal thoughts and behaviors. Serious neuropsychiatric events have been reported in patients taking bupropion for smoking cessation.

Overview

Bupropion is a tetracyclics and unicyclics that is FDA approved for the {{{indicationType}}} of major depressive disorder (MDD)depression, associated with seasonal affective disorder; prophylaxis. There is a Black Box Warning for this drug as shown here. Common adverse reactions include suicidal thoughts and behaviors in adolescents and young adults, neuropsychiatric symptoms and suicide risk in smoking cessation treatment, seizure, hypertension, activation of mania or hypomania, psychosis and other neuropsychiatric reactions, hypersensitivity reactions.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Major depressive disorder (MDD)

• To minimize the risk of seizure, increase the dose gradually [see Warnings and Precautions]. Increases in dose should not exceed 100 mg per day in a 3‑day period. Bupropion Tablets should be swallowed whole and not crushed, divided, or chewed. Bupropion may be taken with or without food.

• The recommended starting dose is 200 mg per day, given as 100 mg twice daily. After 3 days of dosing, the dose may be increased to 300 mg per day, given as 100 mg 3 times daily, with at least 6 hours between successive doses. Dosing above 300 mg per day may be accomplished using the 75- or 100-mg tablets.

• A maximum of 450 mg per day, given in divided doses of not more than 150 mg each, may be considered for patients who show no clinical improvement after several weeks of treatment at 300 mg per day. Administer the 100‑mg tablet 4 times daily to not exceed the limit of 150 mg in a single dose.

• It is generally agreed that acute episodes of depression require several months or longer of antidepressant drug treatment beyond the response in the acute episode. It is unknown whether the dose of Bupropion 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.

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition 1

• Dosing Information

(Dosage)

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition 1

• Developed by: (Organization)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

• (Dosage)

Non–Guideline-Supported Use

Condition 1

• Dosing Information

• There is limited information about Off-Label Non–Guideline-Supported Use of Bupropion in pediatric patients.

Contraindications

• Seizure disorder
• Bulimia or anorexia nervosa
• Patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs

• Condition 5

Warnings

Suicidal thoughts and behaviours; and neuropsychiatry reactions See full prescribing information for complete Boxed Warning. *Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. Monitor for worsening and emergence of suicidal thoughts and behaviors. Serious neuropsychiatric events have been reported in patients taking bupropion for smoking cessation.

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

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

• 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 MDD and other psychiatric disorders. Short-term clinical trials did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24; there was a reduction with antidepressants compared with 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 4,400 subjects. 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 subjects. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger subjects 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 1,000 subjects treated) are provided in Table 1

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Adverse Reactions

Clinical Trials Experience

Central Nervous System

Confusion (major depressive disorder, 8% ), dizziness (6% to 11%), headache (25% to 34% ), insomnia (11% to 20% )

Cardiovascular

Tachycardia (major depressive disorder, 11% )

Respiratory

Nasopharyngitis (seasonal affective disorder, 13% ), pharyngitis (major depressive disorder, 3% to 11% ), upper respiratory infection (seasonal affective disorder, 9% )

Gastrointestinal

Abdominal pain (2% to 9%), constipation (5% to 10%), nausea (13% to 18%), xerostomia (17% to 26%)

Endocrine metabolic

Weight gain (2% to 9% ), weight loss (major depressive disorder, 14% to 19% )

Psychiatric

Agitation (2% to 9%)

Postmarketing Experience

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

(list/description of adverse reactions)

Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

(list/description of adverse reactions)

Drug Interactions

• Potential for Other Drugs to Affect Bupropion

• Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between bupropion and drugs that are inhibitors or inducers of CYP2B6.

• Inhibitors of CYP2B6:Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposure but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of bupropion may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology].

• Inducers of CYP2B6:Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of bupropion may be necessary when coadministered with ritonavir, lopinavir, or efavirenz [see Clinical Pharmacology] but should not exceed the maximum recommended dose.

• Carbamazepine, Phenobarbital, Phenytoin: While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure [see Clinical Pharmacology]. 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.

• Potential for Bupropion to Affect Other Drugs

• Drugs Metabolized by CYP2D6: Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of bupropion 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, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone and flecainide). When used concomitantly with bupropion, 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 and such drugs may require increased doses of the drug see Clinical Pharmacology .

• Drugs That Lower Seizure Threshold

• Use extreme caution when coadministering bupropion with other drugs that lower seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids). Use low initial doses and increase the dose gradually [see Contraindications and Warnings and Precautions].

• 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 concomitantly with these drugs.

• MAO Inhibitors

• Bupropion inhibits the reuptake of dopamine and norepinephrine. Concomitant use of MAOIs and bupropion is contraindicated because there is an increased risk of hypertensive reactions if bupropion is used concomitantly with MAOIs. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAO inhibitor phenelzine. At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of treatment with bupropion. Conversely, at least 14 days should be allowed after stopping bupropion before starting an MAOI antidepressant [see Dosage and Administration and Contraindications].

• Drug-Laboratory Test Interactions

• False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. This is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

• Risk Summary:Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester indicate no increased risk of congenital malformations overall. All pregnancies, regardless of drug exposure, have a background rate of 2% to 4% for major malformations, and 15% to 20% for pregnancy loss. No clear evidence of teratogenic activity was found in reproductive developmental studies conducted in rats and rabbits; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at doses approximately equal to the maximum recommended human dose (MRHD) and greater and decreased fetal weights were seen at doses twice the MRHD and greater. Bupropion should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Clinical Considerations:Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.

• 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.

• No increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). Data from the United Healthcare database and a case-control study (6,853 infants with cardiovascular malformations and 5,763 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 for left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding a possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO (n = 10; adjusted OR = 2.6; 95% CI: 1.2, 5.7), and the Slone Epidemiology case control study did not find increased risk for LVOTO.

• Study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (VSD) are inconsistent and do not allow conclusions regarding a possible association. The Slone Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0) but did not find increased risk for any other cardiovascular malformations studied (including LVOTO as above). The NBDPS and United Healthcare database study did not find an association between first trimester maternal bupropion exposure and VSD.

• For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies.

Animal Data:In studies conducted in rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively (approximately 11 and 7 times the MRHD, respectively, on a mg/m2basis). No clear evidence of teratogenic activity was found in either species; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg/kg/day, approximately equal to the MRHD on a mg/m2 basis) and greater. Decreased fetal weights were observed at 50 mg/kg and greater.

When rats were administered bupropion at oral doses of up to 300 mg/kg/day (approximately 7 times the MRHD on a mg/m2basis) prior to mating and throughout pregnancy and lactation, there were no apparent adverse effects on offspring development.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Bupropion in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Bupropion during labor and delivery.

Nursing Mothers

• Nursing Mothers

• Bupropion and its metabolites are present in human milk. In a lactation study of 10 women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Exercise caution when bupropion is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established [see Boxed Warning and Warnings and Precautions].

Geriatic Use

• Geriatric Use

• Of the approximately 6,000 subjects who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation trials), 275 were aged ≥65 years and 47 were aged ≥75 years. In addition, several hundred subjects aged ≥65 years participated in clinical trials using the immediate-release formulation of bupropion (depression trials). 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 , Use in Specific Populations , and Clinical Pharmacology ].

Gender

There is no FDA guidance on the use of Bupropion with respect to specific gender populations.

Race

There is no FDA guidance on the use of Bupropion with respect to specific racial populations.

Renal Impairment

• Renal Impairment

• Consider a reduced dose and/or dosing frequency of bupropion in patients with renal impairment (Glomerular Filtration Rate: <90 mL/min). Bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see Dosage and Administration and Clinical Pharmacology ].

Hepatic Impairment

• Hepatic Impairment

• In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose of bupropion is 75 mg daily. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see Dosage and Administration and Clinical Pharmacology].

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Bupropion in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Bupropion in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Bupropion Administration in the drug label.

Monitoring

There is limited information regarding Bupropion Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Bupropion and IV administrations.

Overdosage

• Human Overdose Experience

• Overdoses of up to 30 grams or more of bupropion have been reported. Seizure was reported in approximately one-third of all cases. Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, sinus tachycardia, and ECG changes such as conduction disturbances (including QRS prolongation) or arrhythmias. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses.

• Although most patients recovered without sequelae, deaths associated with overdoses of bupropion alone have been reported in patients ingesting large doses of the drug. Multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death were reported in these patients.

• Overdosage Management

Consult a Certified Poison Control Center for up-to-date guidance and advice. Telephone numbers for certified poison control centers are listed in the Physician’s Desk Reference (PDR). Call 1-800-222-1222 or refer to www.poison.org.

There are no known antidotes for bupropion. In case of an overdose, provide supportive care, including close medical supervision and monitoring. Consider the possibility of multiple drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Induction of emesis is not recommended.

Pharmacology

There is limited information regarding Bupropion Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Bupropion Mechanism of Action in the drug label.

Structure

There is limited information regarding Bupropion Structure in the drug label.

Pharmacodynamics

There is limited information regarding Bupropion Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Bupropion Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Bupropion Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Bupropion Clinical Studies in the drug label.

How Supplied

There is limited information regarding Bupropion How Supplied in the drug label.

Storage

There is limited information regarding Bupropion Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

For patient information, please click here.

Precautions with Alcohol

• 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. The consumption of alcohol during treatment with bupropion should be minimized or avoided.

Brand Names

There is limited information regarding Bupropion Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Bupropion Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.