BUPROPION HYDROBROMIDE
Clinical safety rating: safe
MAOIs can increase risk of hypertensive episodes Lowers seizure threshold in a dose-dependent manner.
Bupropion is an aminoketone antidepressant that acts as a norepinephrine-dopamine reuptake inhibitor (NDRI). It also noncompetitively inhibits nicotinic acetylcholine receptors, contributing to smoking cessation efficacy. The exact mechanism for antidepressant effect is unknown but is thought to be related to noradrenergic and dopaminergic modulation.
| Metabolism | Extensively metabolized in the liver via CYP2B6 to hydroxybupropion, threohydrobupropion, and erythrohydrobupropion. CYP2D6 is involved in a minor pathway leading to hydroxybupropion. CYP2B6 is the major enzyme for bupropion hydroxylation. |
| Excretion | Primarily renal (87%), with 10% fecal. Unchanged bupropion in urine <1%. |
| Half-life | Terminal half-life ~20 hours (range 12-30). Clinical note: Steady state in 4-5 days; active metabolites (hydroxybupropion, threohydrobupropion, erythrohydrobupropion) have longer half-lives (20-37 hours) contributing to prolonged effects. |
| Protein binding | 84% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | ~20-30 L/kg (mean 27 L/kg). Clinical meaning: Extensive tissue distribution, including brain. |
| Bioavailability | Oral: 80-90% for immediate-release; sustained-release formulations have similar bioavailability. Note: Extensive first-pass metabolism to active metabolites. |
| Onset of Action | Oral: Improvement in depressive symptoms may begin within 1-2 weeks, with full effect by 4-6 weeks. |
| Duration of Action | Sustained-release formulations provide therapeutic levels over 12-24 hours; immediate-release requires twice daily dosing. Clinical note: Antidepressant effect persists beyond plasma clearance. |
150 mg orally once daily; after 3 days, may increase to 300 mg orally once daily (administer as 150 mg twice daily) for major depressive disorder. For smoking cessation: 150 mg orally once daily for 3 days, then 150 mg orally twice daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For CrCl < 30 mL/min: reduce dose to 150 mg every other day. No adjustment needed for CrCl ≥ 30 mL/min. |
| Liver impairment | Child-Pugh Class A or B: reduce dose to 150 mg every other day. Child-Pugh Class C: contraindicated. |
| Pediatric use | Not recommended for patients < 18 years of age. Safety and efficacy not established. |
| Geriatric use | Initiate at 150 mg once daily; may increase to 150 mg twice daily if tolerated. Elderly patients may have increased sensitivity to adverse effects; consider baseline renal function and adjust accordingly. |
| 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.
| FDA category | Animal |
| Breastfeeding | Bupropion and its metabolites are excreted into breast milk. The milk-to-plasma (M/P) ratio for bupropion is approximately 2.5-8.6 for the parent drug and 1.2-1.8 for metabolites. Relative infant dose is estimated at 2% of maternal weight-adjusted dose. Cases of neonatal seizures and irritability have been reported. Benefit-risk assessment is recommended; consider monitoring infant for adverse effects. |
| Teratogenic Risk |
■ FDA Black Box Warning
Suicidality and Antidepressant Drugs: Bupropion increases the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder 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 in risk with antidepressants compared to placebo in adults aged 65 and older.
| Common Effects | smoking cessation |
| Serious Effects |
Seizure disorder (current or history). Current or prior diagnosis of bulimia or anorexia nervosa. Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. Use of MAOIs within 14 days. Known hypersensitivity to bupropion or any component of formulation.
| Precautions | Seizure risk is dose-dependent; maximum dose 450 mg/day; risk increased with predisposing factors (e.g., seizure disorder, eating disorder). Neuropsychiatric reactions including suicidality, worsening depression, anxiety, agitation, hostility, and abnormal dreams. Can activate mania/hypomania in bipolar disorder. Risk of hypertension, especially when used with nicotine patch. Serotonin syndrome risk with SSRIs/SNRIs. Angle-closure glaucoma risk. Hepatotoxicity reported. |
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| Bupropion is classified as FDA Pregnancy Category C. First trimester exposure is associated with a small increased risk of cardiovascular malformations, particularly ventricular septal defects (OR 1.3-2.5). Second and third trimester exposure may increase risk of preterm birth and low birth weight. Neonatal adaptation syndrome (irritability, feeding difficulties) may occur with late third trimester exposure. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate during pregnancy due to dose-dependent hypertension. Fetal ultrasound for cardiac anatomy if exposed in first trimester. Assess neonatal adaptation if used near term. Monitor maternal weight gain and nutritional status. |
| Fertility Effects | Bupropion does not appear to impair fertility in human studies. In animal studies, no adverse effects on fertility were observed at doses up to 11 times the maximum human dose. Hyperprolactinemia and galactorrhea have been reported rarely, which could affect reproductive function. |
| Food/Dietary | No specific food interactions. Avoid large amounts of alcohol; alcohol may increase seizure risk. Grapefruit juice has no significant interaction. |
| Clinical Pearls | Bupropion hydrobromide is a norepinephrine-dopamine reuptake inhibitor (NDRI) used for major depressive disorder and smoking cessation. It does not cause sexual dysfunction or weight gain, common with SSRIs. Contraindicated in patients with seizure disorders, eating disorders, or abrupt discontinuation of alcohol/sedatives. Dosing: immediate-release (IR) three times daily, sustained-release (SR) twice daily, or extended-release (XL) once daily. Risk of dose-dependent seizures; maximum daily dose 450 mg (IR), 400 mg (SR), 450 mg (XL). Monitor for hypertension, especially when used with nicotine replacement therapy. Use with caution in patients with hepatic or renal impairment. |
| Patient Advice | Take exactly as prescribed; do not crush, chew, or split tablets (especially SR/XL formulations). · May cause dry mouth, insomnia, or headache; take morning doses to minimize insomnia. · Report any rash or itching promptly; may indicate hypersensitivity. · Avoid alcohol while taking bupropion; it can lower seizure threshold. · Seek emergency care for seizures, hallucinations, or severe hypertension. |