Bupropion

WELLBUTRIN SR (bupropion hydrochloride) is indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM). The efficacy of bupropion in the treatment of a major depressive episode was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult subjects with MDD. The efficacy of WELLBUTRIN SR in maintaining an antidepressant response for up to 44 weeks following 8 weeks of acute treatment was demonstrated in a placebo‑controlled trial. WELLBUTRIN SR is an aminoketone antidepressant, indicated for the treatment of major depressive disorder (MDD).

The exact mechanism of the antidepressant action of bupropion is not known but is presumed to be related to noradrenergic and/or dopaminergic mechanisms. Bupropion is a relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine and does not inhibit the reuptake of serotonin. Bupropion does not inhibit monoamine oxidase.

• Starting dose: 150 mg/day. • General: Increase dose gradually to reduce seizure risk. • After 3 days, may increase the dose to 300 mg/day, given as 150 mg twice daily at an interval of at least 8 hours. • Usual target dose: 300 mg/day as 150 mg twice daily. • Maximum dose: 400 mg/day, given as 200 mg twice daily, for patients not responding to 300 mg/day. • Periodically reassess the dose and need for maintenance treatment. • Moderate to severe hepatic impairment: 100 mg daily or 150 mg every other day. • Mild hepatic impairment: Consider reducing the dose and/or frequency of dosing. • Renal impairment: Consider reducing the dose and/or frequency.

• WELLBUTRIN SR is contraindicated in patients with a seizure disorder. • WELLBUTRIN SR is contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with the immediate‑release formulation of bupropion. • WELLBUTRIN SR is contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. • The use of MAOIs (intended to treat psychiatric disorders) concomitantly with WELLBUTRIN SR or within 14 days of discontinuing treatment with WELLBUTRIN SR is contraindicated.

Boxed warning (suicidal thoughts and behaviors suicidality and antidepressant drugs): Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects over age 24, there was a reduction in risk with antidepressant use in subjects aged 65 and older. • Neuropsychiatric adverse events during smoking cessation: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide.

The following adverse reactions are discussed in greater detail in other sections of the labeling: • Suicidal thoughts and behaviors in adolescents and young adults • Neuropsychiatric symptoms and suicide risk in smoking cessation treatment • Seizure • Hypertension • Activation of mania or hypomania • Psychosis and other neuropsychiatric reactions • Angle-closure glaucoma • Hypersensitivity reactions Most common adverse reactions (incidence ≥5% and ≥2% more than placebo rate) are: headache, dry mouth, nausea, insomnia, dizziness, pharyngitis, constipation, agitation, anxiety, abdominal pain, tinnitus, tremor, palpitation, myalgia, sweating, rash, and anorexia.

• CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based on clinical response, but should not exceed the maximum recommended dose. • Drugs metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). Consider dose reduction when using with bupropion. • Digoxin: May decrease plasma digoxin levels. Monitor digoxin levels. • Drugs that lower seizure threshold: Dose WELLBUTRIN SR with caution.

Store at room temperature, 20° to 25°C (68° to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from light and moisture.