BUPROPION HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Bupropion is a relatively weak inhibitor of neuronal dopamine and norepinephrine reuptake, but its clinical effects are thought to be mediated by these mechanisms. It also has weak antagonistic properties at nicotinic acetylcholine receptors.
| Metabolism | Extensively metabolized in the liver via CYP2B6 to hydroxybupropion, and to a lesser extent via CYP2C19, CYP1A2, CYP2D6, and CYP3A4. Hydroxybupropion is further metabolized via glucuronidation. |
| Excretion | Renal: 87% (primarily as metabolites, <0.5% unchanged); biliary/fecal: 10%; hepatic metabolism by CYP2B6 to active metabolites (hydroxybupropion, threohydrobupropion, erythrohydrobupropion). |
| Half-life | Bupropion: ~21 hours (11-30 hours); hydroxybupropion: ~20 hours; threohydrobupropion: ~37 hours; erythrohydrobupropion: ~33 hours. Clinical context: Steady-state reached in 5-8 days; extended half-life of metabolites contributes to prolonged effects and accumulation. |
| Protein binding | Bupropion: 84% (primarily to albumin). Hydroxybupropion: 100% (non-linear, high binding); other metabolites: ~50%. |
| Volume of Distribution | Bupropion: 19.2–27.5 L/kg (Vd/F) indicating extensive tissue distribution; crosses blood-brain barrier and placenta. Clinical meaning: Large Vd suggests significant extravascular distribution, requiring loading dose for rapid effect. |
| Bioavailability | Oral (IR/SR/XL): 5-20% (extensive first-pass metabolism by CYP2B6). Bioavailability increased with food (peak concentration by 11-25% for SR). |
| Onset of Action | Immediate-release: 1-2 hours; sustained-release: ~3 hours; extended-release: ~4 hours. Clinical effect (antidepressant) may require 2-4 weeks. Smoking cessation: reduction in cravings begins within days. |
| Duration of Action | Immediate-release: 6-8 hours (dosed 3 times daily); sustained-release: ~12 hours (dosed twice daily); extended-release: ~24 hours (dosed once daily). Clinical note: Duration sufficient for once-daily dosing with XL formulation; smoking cessation efficacy sustained over 7-12 weeks of treatment. |
150 mg orally once daily (immediate-release) or 150 mg orally twice daily (sustained-release); maximum 300 mg/day for immediate-release and 400 mg/day for sustained-release. Extended-release: 150 mg orally once daily, titrate to 300 mg once daily. Typical target 300 mg/day in divided doses.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For CrCl <30 mL/min: reduce dose and/or frequency; immediate-release: 150 mg every other day; sustained/extended-release: maximum 150 mg every other day. Not recommended in end-stage renal disease. |
| Liver impairment | Child-Pugh Class A: no adjustment needed. Child-Pugh Class B: reduce dose to 50% and/or use extended interval (e.g., 150 mg every other day). Child-Pugh Class C: contraindicated. |
| Pediatric use | Weight-based guidelines not established for immediate-release in patients <18 years. For extended-release (for depression): 12-17 years: start 150 mg once daily, may increase after 4 days to 300 mg once daily. Do not exceed 300 mg/day. |
| Geriatric use | Start at lower dose (e.g., 100-150 mg/day immediate-release or 150 mg/day extended-release) due to increased risk of adverse effects, renal impairment, and comorbidities. Titrate slowly. Monitor for agitation, confusion, and serotonin syndrome. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can increase risk of hypertensive episodes Lowers seizure threshold in a dose-dependent manner.
| Breastfeeding | Bupropion is excreted into breast milk in low concentrations. The milk-to-plasma ratio is approximately 2.5. Relative infant dose is about 2% of maternal weight-adjusted dose. Adverse effects in breastfed infants are rare but include irritability, poor feeding, and seizures. Caution is advised, especially in preterm or low birth weight infants. Consider risk-benefit; alternative antidepressants may be preferred. |
| Teratogenic Risk | Bupropion is classified as FDA Pregnancy Category C. First trimester exposure is associated with a small increased risk of cardiovascular malformations (primarily left ventricular outflow tract obstruction), with an absolute risk of approximately 1.4% vs 1% baseline. Second and third trimester exposure may increase risk of preterm birth and low birth weight; no consistent association with major malformations in late pregnancy. Neonatal adaptation syndrome may occur with third trimester exposure, including jitteriness, irritability, and feeding difficulties. |
■ FDA Black Box Warning
Bupropion is associated with an increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Common Effects | smoking cessation |
| Serious Effects |
Seizure disorder; current or prior diagnosis of bulimia or anorexia nervosa; abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs; concomitant use with MAOIs or within 14 days of discontinuing MAOIs; history of head trauma or CNS tumor; concomitant use with other bupropion-containing products.
| Precautions | Risk of seizure (dose-dependent); activation of mania/hypomania; hypertension; psychosis; angle-closure glaucoma; hepatotoxicity; weight loss; hypersensitivity reactions. Monitor for neuropsychiatric symptoms in smoking cessation patients. |
| Food/Dietary |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly due to bupropion's stimulant properties. Assess for signs of serotonin toxicity if used with other serotonergic agents. Fetal monitoring includes ultrasound for growth and anatomy, especially if exposure occurs in first trimester. Newborn monitoring for neonatal adaptation syndrome for at least 48 hours after delivery. |
| Fertility Effects | Bupropion has not been associated with significant adverse effects on fertility in humans. In animal studies, no impairment of fertility was observed at doses up to 5 times the maximum recommended human dose. Clinically, bupropion may increase prolactin levels, but hyperprolactinemia is uncommon. No evidence of effect on spermatogenesis or oocyte development. |
| Avoid excessive alcohol consumption as it lowers seizure threshold. No specific food restrictions, but maintain a balanced diet to mitigate potential weight fluctuations. Bupropion does not interact significantly with tyramine-containing foods. |
| Clinical Pearls | Bupropion is contraindicated in patients with seizure disorder or eating disorders. It has a lower risk of sexual dysfunction and weight gain compared to other antidepressants. Monitor blood pressure regularly due to dose-dependent hypertension risk. Avoid in patients with abrupt discontinuation of alcohol, benzodiazepines, or sedatives. Use with caution with MAOIs, requiring a 14-day washout. |
| Patient Advice | Take exactly as prescribed; do not crush or chew tablets. · It may cause seizures, especially at higher doses or if you have a history of seizures, head injury, or eating disorders. · Report any unusual changes in mood, behavior, or suicidal thoughts immediately. · It can increase blood pressure; monitor regularly and avoid alcohol or other substances that can lower seizure threshold. · Do not abruptly stop; taper under medical supervision to avoid withdrawal symptoms. Avoid taking MAOIs within 14 days. |