WELLBUTRIN SR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WELLBUTRIN SR (WELLBUTRIN SR).
Wellbutrin SR (bupropion) is an atypical antidepressant. Its mechanism of action is not fully understood, but it is thought to involve inhibition of dopamine and norepinephrine reuptake in the brain, with minimal effect on serotonin reuptake. It also acts as a nicotinic acetylcholine receptor antagonist.
| Metabolism | Extensively metabolized in the liver via CYP2B6, with hydroxybupropion as the major active metabolite. Minor pathways include CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4. |
| Excretion | Primarily renal (87% as bupropion and its metabolites, with 10% as unchanged drug); 10% fecal. |
| Half-life | Terminal half-life of bupropion is approximately 21 hours (±9 hours); for the active metabolite hydroxybupropion, half-life is ~20-27 hours. Steady state reached within 5-8 days. |
| Protein binding | 84% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 19-31 L/kg for bupropion; extensive tissue distribution. |
| Bioavailability | SR formulation: absolute bioavailability ~87% (due to extensive first-pass metabolism, bupropion itself has low systemic availability but active metabolites contribute). |
| Onset of Action | 2-4 weeks for therapeutic antidepressant effect; immediate-release peak plasma levels at 2 hours, sustained-release (SR) at 3 hours. |
| Duration of Action | Duration of clinical effect is 24 hours with SR formulation, allowing once-daily dosing; sustained action maintained by active metabolites. |
150 mg orally once daily, may increase to 150 mg twice daily after 3 days if needed. Maximum 300 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | CrCl <30 mL/min: not recommended. CrCl 30-60 mL/min: reduce dose or increase interval (e.g., 150 mg every 48 hours). |
| Liver impairment | Child-Pugh Class B: reduce dose to 100 mg/day or 150 mg every other day. Class C: contraindicated. |
| Pediatric use | Not approved for pediatric use. Clinical trials insufficient to establish safety and efficacy in patients <18 years. |
| Geriatric use | Start at 150 mg daily; titrate slowly due to increased risk of seizures and comorbidities. Monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for WELLBUTRIN SR (WELLBUTRIN SR).
| Breastfeeding | Bupropion and its metabolites are excreted into breast milk. M/P ratio: approximately 2.5 to 8.6 for bupropion; active metabolite hydroxybupropion M/P ratio ~1.3 to 8.8. Relative infant dose (RID) estimated 2% of maternal weight-adjusted dose. Limited reports of adverse effects (seizure, irritability) in infants; use caution and monitor for agitation, poor feeding, or seizures. |
| Teratogenic Risk | FDA Pregnancy Category B. First trimester: limited human data do not show increased risk of major congenital malformations overall; some studies suggest small increased risk of cardiovascular defects (e.g., ventricular septal defect) but not confirmed. Second and third trimesters: no specific malformation risk; may be associated with preterm birth and low birth weight. Neonatal effects: risk of neonatal withdrawal syndrome (irritability, feeding difficulties, respiratory depression) after late third-trimester exposure; no known risk of persistent pulmonary hypertension. |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thinking and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. All patients starting antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior.
| Serious Effects |
["Seizure disorder or history of seizures.","Current or prior diagnosis of bulimia or anorexia nervosa.","Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs.","Known hypersensitivity to bupropion or any component of the formulation.","Abrupt discontinuation of alcohol, benzodiazepines, or other sedatives (relative contraindication due to increased seizure risk).","Pregnancy (only if potential benefit justifies potential risk; avoid in first trimester)."]
| Precautions | ["Seizure risk: dose-dependent; increased in patients with predisposing factors (e.g., head trauma, CNS tumor, eating disorders, abrupt discontinuation of alcohol/benzodiazepines).","Neuropsychiatric reactions (including suicidality, hostility, agitation) during smoking cessation.","Hypertension: monitor blood pressure, especially in patients with pre-existing hypertension or those using nicotine replacement therapy.","Activation of mania/hypomania in patients with bipolar disorder.","Angle-closure glaucoma: may cause mydriasis.","Hepatotoxicity: rare but reported.","Serotonin syndrome when used with other serotonergic drugs."] |
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| Fetal Monitoring | Monitor maternal blood pressure (bupropion may increase BP). Fetal ultrasound for growth and anatomy. Neonatal monitoring for withdrawal symptoms (irritability, feeding intolerance, respiratory distress) during first 48 hours. Assess for signs of neonatal toxicity if maternal dose >300 mg/day. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment. May improve sexual function in women with depression, potentially benefiting fertility indirectly. |