APLENZIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for APLENZIN (APLENZIN).
Bupropion is an aminoketone antidepressant that inhibits the reuptake of norepinephrine and dopamine, with no significant effect on serotonin. The exact mechanism of antidepressant action is unknown but is thought to be mediated by noradrenergic and dopaminergic pathways.
| Metabolism | Primarily hepatic via CYP2B6 isoenzyme; major metabolites include hydroxybupropion, threohydrobupropion, and erythrohydrobupropion. |
| Excretion | Primarily renal (87% recovered in urine) with 10% fecal elimination. Unchanged bupropion accounts for <1% of renal excretion; metabolites (hydroxybupropion, threohydrobupropion, erythrohydrobupropion) predominate. |
| Half-life | Mean terminal half-life of bupropion is 21 hours (SD ±9 hours). Steady state achieved within 8 days. Metabolites have longer half-lives: hydroxybupropion ~24 hours, threohydrobupropion ~37 hours, erythrohydrobupropion ~34 hours. |
| Protein binding | 82–88% bound to plasma proteins, primarily albumin. Metabolites are less extensively bound (hydroxybupropion 42%). |
| Volume of Distribution | 19–27 L/kg (1,500–2,000 L for 70 kg). Large Vd indicates extensive tissue distribution, crossing blood-brain barrier to achieve CNS concentrations. |
| Bioavailability | Bioavailability of Aplenzin (bupropion hydrobromide): approximately 100% for the oral dose, with minimal first-pass metabolism due to formulation. Absolute bioavailability of bupropion from immediate-release is 5–20% due to extensive first-pass; sustained-release (Aplenzin) reduces variability but similar bioavailability. |
| Onset of Action | Therapeutic effect for smoking cessation and depression typically begins after 1–2 weeks of dosing. Maximum effect for smoking cessation may require up to 10 weeks. |
| Duration of Action | Sustained-release formulation: 24-hour dosing interval. Clinical effects persist throughout the dosing interval; steady-state concentrations maintained with once-daily dosing. Withdrawal effects may occur upon abrupt discontinuation. |
APLENZIN (bupropion hydrobromide) extended-release tablets: Initial dose 174 mg orally once daily in the morning; after 4 days, increase to 348 mg once daily. Maximum dose 348 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For moderate to severe renal impairment (eGFR <30 mL/min/1.73 m2): maximum dose 174 mg every other day. Contraindicated in end-stage renal disease (eGFR <15 mL/min/1.73 m2) due to risk of accumulation. |
| Liver impairment | Child-Pugh Class A (mild): reduce dose to 174 mg every other day. Child-Pugh Class B (moderate): reduce dose to 174 mg every other day. Child-Pugh Class C (severe): contraindicated. |
| Pediatric use | Not approved for pediatric use. Safety and efficacy in patients <18 years have not been established; no weight-based dosing recommended. |
| Geriatric use | In elderly patients, consider lower starting dose (174 mg daily) due to age-related decline in renal and hepatic function; monitor for hypertension and neuropsychiatric adverse effects. Maximum dose 348 mg/day if tolerated. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for APLENZIN (APLENZIN).
| Breastfeeding | Present in human milk in low concentrations. Milk-to-plasma ratio approximately 2.5 (based on bupropion). Infant relative dose is 2% of maternal weight-adjusted dose. Monitor infant for irritability, poor feeding, and weight gain. Consider benefits of breastfeeding and maternal need for drug. |
| Teratogenic Risk | Pregnancy category C. First trimester: Increased risk of cardiovascular malformations (e.g., ventricular septal defect) associated with bupropion, though absolute risk is low. Second and third trimesters: Risk of persistent pulmonary hypertension of the newborn (PPHN) reported with bupropion exposure after 20 weeks; data limited for APLENZIN specifically. Late third trimester: Potential for neonatal withdrawal symptoms including irritability, feeding difficulties, and respiratory distress. |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Monitor closely for worsening and emergence of suicidal thoughts and behaviors.
| Serious Effects |
["Seizure disorder","Current or prior diagnosis of bulimia or anorexia nervosa","Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs","Use of MAO inhibitors within 14 days","Known hypersensitivity to bupropion or any component of the formulation"]
| Precautions | ["Seizure risk: dose-related; avoid in patients with seizure disorders or conditions that lower seizure threshold","Neuropsychiatric reactions: including psychosis, hallucinations, mania, and paranoia","Hypertension: monitor blood pressure, especially when used with nicotine replacement therapy","Hepatotoxicity: rare but severe liver injury reported","Hypersensitivity: angioedema, urticaria, or other allergic reactions"] |
| Food/Dietary | No specific food restrictions. Grapefruit and grapefruit juice have not been reported to interact significantly. Avoid excessive alcohol consumption due to increased seizure risk. |
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| Fetal Monitoring | Maternal: Monitor blood pressure due to dose-related hypertension risk. Fetal: Fetal echocardiography between 20-24 weeks if first-trimester exposure (given cardiovascular risk). Neonatal: Observe for signs of abstinence syndrome (irritability, tremors, feeding difficulties) for 48-72 hours after delivery if used in third trimester. |
| Fertility Effects | No human data on fertility effects with APLENZIN. Animal studies (bupropion) at 7 times MRHD showed no impairment of fertility. Hyperprolactinemia and galactorrhea reported with bupropion, potentially affecting ovulation; clinical significance unknown. |
| Clinical Pearls | APLENZIN (bupropion hydrobromide) is an aminoketone antidepressant that inhibits dopamine and norepinephrine reuptake. It does not cause sexual dysfunction or weight gain, making it a preferred agent in patients with these concerns. It lowers seizure threshold, especially at higher doses (max 450 mg/day, but for APLENZIN 522 mg is equivalent to 450 mg bupropion HCl). Avoid in patients with seizure disorders, eating disorders, or abrupt discontinuation of alcohol/sedatives. It is also used for smoking cessation (brand name Zyban). Monitor for hypertension, as it can cause dose-dependent blood pressure increases. APLENZIN is a once-daily extended-release tablet; instruct patients not to crush or chew. |
| Patient Advice | Take APLENZIN exactly as prescribed, usually once daily in the morning, with or without food. · Swallow the tablet whole; do not crush, chew, or cut it. · Inform your doctor if you have a history of seizures, head injury, eating disorder, or high blood pressure. · Avoid alcohol while taking APLENZIN as it may increase seizure risk. · Do not stop taking this medication abruptly; consult your doctor for a gradual dose reduction. · Contact your doctor immediately if you experience severe headache, confusion, blurred vision, or seizures. · APLENZIN may cause insomnia; if persistent, take in the morning. · It may take several weeks for full therapeutic effect in depression. |