Bupropion Hydrochloride

Approved Indications:

• Major Depressive Disorder (MDD): Treatment of depressive episodes, including unipolar depression.
• Seasonal Affective Disorder (SAD): Prevention of depressive episodes in patients with a history of seasonal patterns.
• Smoking Cessation Aid: As part of a comprehensive smoking cessation program.

Clinically Accepted Off-label Uses:

• Attention-Deficit/Hyperactivity Disorder (ADHD): In adults and adolescents intolerant to stimulants.
• Bipolar Depression (Adjunct): As adjunctive therapy with mood stabilizers.
• Obesity: As part of bupropion/naltrexone combination therapy.
• Sexual Dysfunction (SSRI-induced): To counteract reduced libido in SSRI-treated patients.

Adults:

• MDD: Start with 150 mg once daily in the morning. May increase to 300 mg/day as 150 mg twice daily. Max: 400 mg/day (sustained-release), 450 mg/day (extended-release), in divided doses.
• SAD: Initiate 150 mg once daily in autumn; increase to 300 mg once daily after 7 days. Discontinue in early spring.
• Smoking Cessation: 150 mg once daily for 3 days, then 150 mg twice daily. Start 1–2 weeks before quit date. Continue for 7–12 weeks.

Pediatrics:

• Not FDA-approved. Off-label in ADHD: Dosing individualized.

Elderly:

• Use with caution. Start at lower end of dosing range; monitor for adverse reactions.

Hepatic Impairment:

• Mild-to-moderate: Reduce frequency or dose.
• Severe: Max 75 mg/day.

Renal Impairment:

• Adjust dose based on creatinine clearance; reduce frequency.

Administration:

• Take with or without food.
• Do not crush or chew sustained/extended-release tablets.

Bupropion Hydrochloride is a norepinephrine-dopamine reuptake inhibitor (NDRI). It inhibits the neuronal uptake of norepinephrine and dopamine, enhancing neurotransmission in brain regions associated with mood, reward, and motivation. Unlike SSRIs, it has minimal effect on serotonin reuptake, reducing risk of serotonergic side effects. Its nicotinic receptor antagonism contributes to its efficacy in smoking cessation by reducing withdrawal symptoms and nicotine cravings.

• Absorption: Rapidly absorbed. Bioavailability ~5–20% due to extensive first-pass metabolism.
• Time to Peak: ~3 hours (IR), 5 hours (SR), and 5–8 hours (XL).
• Distribution: Widely distributed; ~84% plasma protein binding.
• Metabolism: Hepatic via CYP2B6 to active metabolites (hydroxybupropion, threohydrobupropion, erythrohydrobupropion).
• Elimination Half-life: Parent drug: ~21 hours; active metabolites: 20–37 hours.
• Excretion: Mainly renal (87%) and fecal (10%).

• Pregnancy: Category C. Animal studies show adverse fetal effects; no adequate human studies. Use only if benefits outweigh risks.
• Lactation: Excreted in breast milk in small amounts. Use with caution; monitor infant for irritability, poor feeding, or seizures.

• Seizure Risk: Dose-dependent; avoid exceeding max recommended dose.
• Neuropsychiatric Symptoms: Suicidal ideation, agitation, hallucinations—especially during smoking cessation.
• Hypertension: Monitor blood pressure, especially in combination with nicotine patches.
• Liver & Kidney Impairment: Dose adjustments required; monitor function.
• Angle-Closure Glaucoma: May precipitate attack in susceptible individuals.
• Mania/Hypomania Risk: Monitor bipolar patients.

Common:

• CNS: Insomnia, agitation, anxiety, headache, tremor
• GI: Dry mouth, nausea, constipation
• General: Weight loss, sweating

Serious/Rare:

• Seizures
• Hypertensive crisis
• Severe allergic reactions (e.g., Stevens-Johnson Syndrome)
• Visual disturbances
• Psychiatric effects: Mania, psychosis, suicidal thoughts

Timing & Severity:

• Many effects occur within first 1–2 weeks.
• Seizure risk increases with high doses or predisposition (e.g., eating disorders).

• Seizure Risk: Dose-dependent; avoid exceeding max recommended dose.
• Neuropsychiatric Symptoms: Suicidal ideation, agitation, hallucinations—especially during smoking cessation.
• Hypertension: Monitor blood pressure, especially in combination with nicotine patches.
• Liver & Kidney Impairment: Dose adjustments required; monitor function.
• Angle-Closure Glaucoma: May precipitate attack in susceptible individuals.
• Mania/Hypomania Risk: Monitor bipolar patients.

Common:

• CNS: Insomnia, agitation, anxiety, headache, tremor
• GI: Dry mouth, nausea, constipation
• General: Weight loss, sweating

Serious/Rare:

• Seizures
• Hypertensive crisis
• Severe allergic reactions (e.g., Stevens-Johnson Syndrome)
• Visual disturbances
• Psychiatric effects: Mania, psychosis, suicidal thoughts

Timing & Severity:

• Many effects occur within first 1–2 weeks.
• Seizure risk increases with high doses or predisposition (e.g., eating disorders).

• MAO Inhibitors: Risk of hypertensive crisis.
• Drugs lowering seizure threshold: E.g., antipsychotics, systemic steroids, quinolones, theophylline.
• Alcohol: Increases risk of neuropsychiatric effects and seizures.
• CYP2B6 inhibitors (e.g., clopidogrel): May increase bupropion levels.
• CYP2D6 substrates (e.g., metoprolol, tamoxifen): Bupropion inhibits CYP2D6; may increase levels of these drugs.
• Levodopa and Amantadine: Increased risk of neurotoxicity.

• FDA Warning (Neuropsychiatric Symptoms): Updated guidance emphasizing risk during smoking cessation; all patients should be monitored.
• EMA Advisory: Reiteration on seizure risk, especially in anorexia/bulimia.
• Combination Therapy (Bupropion + Naltrexone): Endorsed for weight management in specific patient populations.

• Temperature: Store below 25°C (77°F); excursions up to 30°C allowed.
• Humidity/Light: Keep in a dry place, away from light and moisture.
• Handling: Do not crush, split, or chew tablets.
• Container: Store in tightly closed, original container.
• XL/SR Formulations: Protect from extreme heat and direct sunlight.