Bupropion: Important Safety Information (ISI)

Read this information carefully before starting bupropion. Discuss any questions with your provider.

What Is Bupropion?

Bupropion is a norepinephrine and dopamine reuptake inhibitor (NDRI) FDA-approved for the treatment of major depressive disorder, seasonal affective disorder, and as an aid to smoking cessation (Zyban®). It is also a component of Contrave® (naltrexone + bupropion), FDA-approved for chronic weight management. Bupropion is prescribed off-label for ADHD and as an adjunct in weight loss protocols.

Boxed Warning

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS. Antidepressants, including bupropion, increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment and at times of dosage changes. Bupropion is not approved for use in pediatric patients.

Contraindications

• Seizure disorder
• Current or prior diagnosis of bulimia or anorexia nervosa (higher seizure incidence observed)
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
• Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping an MAOI
• Known hypersensitivity to bupropion or any of the inactive ingredients

Warnings and Precautions

• Suicidal Thoughts and Behaviors: See Boxed Warning. Monitor closely, especially in the early weeks of treatment and after dose changes.
• Seizures: Risk is dose-dependent. Discontinue and do not restart in patients who experience a seizure during therapy.
• Hypertension: May cause elevated blood pressure. Monitor before and during therapy.
• Activation of Mania or Hypomania: Screen for bipolar disorder before initiation.
• Psychosis, Confusion, and Other Neuropsychiatric Reactions: Reported in postmarketing experience. Monitor for behavioral changes.
• Angle-Closure Glaucoma: May trigger angle-closure attack in susceptible patients.
• Hypersensitivity Reactions: Anaphylactoid and serious skin reactions reported. Discontinue if reactions develop.
• Cardiovascular Effects: Use with caution in patients with recent myocardial infarction or unstable cardiac disease.
• Hepatotoxicity: Cases of liver injury reported. Monitor liver function if symptoms develop.

Most Common Adverse Reactions

Most common adverse reactions reported in clinical trials of bupropion:

• Insomnia
• Dry mouth
• Headache
• Nausea
• Constipation
• Dizziness
• Agitation or anxiety
• Tremor
• Weight loss
• Increased sweating

Drug Interactions

Bupropion is metabolized to its active metabolite hydroxybupropion by CYP2B6. Drugs that inhibit CYP2B6 (e.g., ticlopidine, clopidogrel) may increase bupropion exposure. Bupropion is a CYP2D6 inhibitor and may increase exposure to drugs metabolized by CYP2D6 (e.g., certain antidepressants, beta-blockers, antipsychotics, tamoxifen). Avoid use with MAOIs (within 14 days). Use caution with drugs that lower the seizure threshold.

Use in Specific Populations

• Pregnancy: Limited human data. Use only if clearly needed and benefit outweighs risk.
• Lactation: Bupropion and its metabolites are present in human milk. Consider risk and benefit.
• Pediatric Use: Safety and effectiveness not established. Not approved for pediatric patients.
• Geriatric Use: May be more sensitive to effects; consider lower starting doses.
• Renal Impairment: Reduce dose and frequency in patients with moderate to severe renal impairment.
• Hepatic Impairment: Use with caution; reduce dose and frequency in moderate to severe impairment.