ZYBAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYBAN (ZYBAN).
Bupropion is a selective dopamine and norepinephrine reuptake inhibitor with weak inhibition of serotonin reuptake. Its mechanism in smoking cessation and depression is not fully understood.
| Metabolism | Primarily hepatic via CYP2B6 to hydroxybupropion; also via reduction to threohydrobupropion and erythrohydrobupropion. CYP2D6 is involved in minor hydroxylation pathways. Hydroxybupropion is active. |
| Excretion | Renal excretion accounts for approximately 87% of an oral dose, with 42% as unchanged bupropion and its active metabolites (hydroxybupropion, threohydrobupropion, erythrohydrobupropion). Fecal excretion is minimal at <10%. |
| Half-life | The terminal elimination half-life of bupropion is approximately 21 hours (range 18-24 h), while its active metabolites have longer half-lives: hydroxybupropion ~20 h, threohydrobupropion ~37 h, erythrohydrobupropion ~33 h. Steady state is achieved within 8 days. |
| Protein binding | Bupropion is 82-88% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 20-27 L/kg, indicating extensive tissue distribution, with a high Vd consistent with lipophilicity and penetration into the central nervous system. |
| Bioavailability | Oral bioavailability of bupropion is approximately 5-20% due to extensive first-pass metabolism. Hepatic metabolism is significant, producing active metabolites that contribute to clinical effects. |
| Onset of Action | Oral: Onset of clinical effect (antidepressant) typically occurs within 2-4 weeks of regular dosing. Smoking cessation: reduction in cravings may be noted within the first week, but full effect may require several weeks. |
| Duration of Action | Duration of antidepressant effect is sustained with continued dosing; withdrawal may lead to relapse. For smoking cessation, therapy is usually continued for 7-12 weeks. The prolonged half-life of metabolites contributes to extended action. |
| Action Class | Norepinephrine-dopamine reuptake inhibitor (NDRI) |
| Brand Substitutes | Nicoalarm 150mg Tablet SR, Bupdep 150mg Tablet SR, Buprex 150mg Tablet SR, Atydep 150mg Tablet SR, Bupozen 150 Tablet SR |
150 mg orally once daily for 3 days, then increase to 150 mg twice daily for a total treatment duration of 7-12 weeks.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No specific dose adjustment for GFR ≥30 mL/min; avoid use in severe renal impairment (GFR <30 mL/min) due to increased risk of seizures; maximum dose 150 mg once daily if GFR 30-50 mL/min. |
| Liver impairment | Child-Pugh A (mild): no adjustment; Child-Pugh B (moderate): maximum dose 150 mg once daily; Child-Pugh C (severe): avoid use. |
| Pediatric use | Not approved for use in patients under 18 years of age; safety and efficacy not established. |
| Geriatric use | Initiate at 150 mg once daily; monitor closely for seizure risk and adverse effects; consider lower maintenance dose if tolerability issues arise. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYBAN (ZYBAN).
| Breastfeeding | Bupropion is excreted into human milk. The milk-to-plasma ratio is approximately 2.5. Average infant exposure is estimated at 2% of the maternal weight-adjusted dose. Cases of seizures in breastfed infants have been reported, likely related to high maternal doses. Breastfeeding is generally not recommended due to potential serious adverse effects in the infant, particularly if the mother requires high doses. |
| Teratogenic Risk | First trimester: Data from cohort studies suggest a small increased risk of major congenital malformations, particularly cardiovascular defects, with bupropion exposure. Second trimester: No specific increased risk identified. Third trimester: Possible neonatal withdrawal symptoms including irritability, feeding difficulties, and respiratory distress. Bupropion is an aminoketone antidepressant; animal studies showed no teratogenicity at clinically relevant doses. |
■ FDA Black Box Warning
Bupropion is associated with increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Balance this risk with clinical need.
| Serious Effects |
["Hypersensitivity to bupropion or any component","Seizure disorder","Current or prior diagnosis of bulimia or anorexia nervosa","Abrupt discontinuation of alcohol or sedatives","Concomitant MAOIs (within 14 days)","Hepatic cirrhosis"]
| Precautions | ["Neuropsychiatric events including suicidal thoughts and behaviors","Seizure risk, especially in patients with predisposing factors (e.g., eating disorders, head trauma, concomitant drugs that lower seizure threshold)","Activation of mania/hypomania in bipolar disorder","Increased blood pressure and hypertension","Angle-closure glaucoma","Hepatotoxicity","Allergic reactions including anaphylaxis"] |
Loading safety data…
| Fetal Monitoring | Monitor for maternal blood pressure and heart rate due to bupropion's potential for elevating these. Monitor fetal growth and well-being via regular ultrasound. Assess for neonatal adaptation syndrome after delivery, including irritability, hypertonia, feeding issues, and respiratory distress. Evaluate for maternal seizures, especially in those with predisposing factors. |
| Fertility Effects | Animal studies have shown no impairment of fertility. Human data are insufficient; however, bupropion may cause hormonal changes that could affect menstrual cyclicity. No direct adverse effects on spermatogenesis have been reported. |