A once-daily tablet for major depressive disorder

COMPANY: Sanofi Aventis

PHARMACOLOGIC CLASS: Antidepressant (aminoketone)

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ACTIVE INGREDIENT: Bupropion HBr 174mg (equiv. to bupropion HCl 150mg), 348mg (equiv. to bupropion HCl 300mg), 522mg (equiv. to bupropion HCl 500mg); ext-rel tabs.

INDICATION: Major depressive disorder.

PHARMACOLOGY: Aplenzin is a once-daily, extended-release tablet formulation of bupropion HBr. The mechanism of action of bupropion in treating depression is not known, but it is likely mediated by its effects on norepinephrine and dopamine.

CLINICAL TRIALS: The approval of Aplenzin was based on its bioequivalence to another form of bupropion, Wellbutrin XL (bupropion HCl, from GlaxoSmithKline). In a 10-day study comparing the use of Aplenzin 348mg once daily to Wellbutrin XL 300mg once daily, the peak levels and the extent of absorption for the parent drug and its metabolites were shown to be equivalent. The effectiveness of bupropion in the treatment of depression was established using a short-acting formulation of bupropion HCl in two 4-week placebo-controlled trials in adult inpatients and a 6-week study in adult outpatients. These studies showed the effectiveness of bupropion HCl on the Hamilton Depression Rating Scale total score, the depressed mood item from that scale, and the Clinical Global Impressions severity score. In another trial, a 44-week study demonstrated the long-term efficacy of bupropion in responders.

ADULTS: Swallow whole. Take in the AM. Initially 174mg once daily; may increase to target maintenance 348mg once daily on day 4; may then increase to max 522mg once daily if inadequate response after 4 weeks. Severe hepatic cirrhosis: max 174mg/48 hours. Renal or mild-moderate hepatic dysfunction: reduce dose and/or frequency. Switching from other forms: may use equivalent dose on once-daily basis. Reevaluate periodically.

CHILDREN: Not recommended.

CONTRAINDICATIONS: Seizure disorder. Bulimia. Anorexia nervosa. Within 14 days of MAOIs. Abrupt withdrawal of sedatives or alcohol. Concomitant other forms of bupropion (eg, Zyban, Wellbutrin).

PRECAUTIONS: Seizure risk or history. Discontinue if seizure occurs; do not restart. Bipolar disorder. Psychosis. Unstable heart disease. CHF. Recent MI. Hepatic or renal dysfunction. Suicidal tendencies (monitor). Maintain at lowest effective dose. Write Rx for smallest practical amount. Labor & delivery. Pregnancy (Cat.C). Nursing mothers: not recommended.

INTERACTIONS: See Contraindications. Avoid alcohol. May be potentiated by CYP2B6 substrates or inhibitors, efavirenz, fluvoxamine, nelfinavir, paroxetine, ritonavir, sertraline. Caution with drugs (eg, antipsychotics) or factors (eg, opiate addiction, excessive use of alcohol or sedatives, diabetes) that lower seizure threshold. Caution with levodopa, amantadine, and with drugs metabolized by CYP2B6 or CYP2D6 including tricyclic antidepressants, SSRIs, antipsychotics, β-blockers, Class 1C antiarrhythmics; consider dose reduction. Antagonized by carbamazepine, phenobarbital, phenytoin. Monitor for hypertension with nicotine patches.

ADVERSE REACTIONS: CNS stimulation, dry mouth, GI upset, dizziness, pharyngitis, palpitation, abdominal pain, sweating, tinnitus, anorexia, urinary frequency, rash (may be serious, eg, Stevens-Johnson syndrome), myalgia, neuropsychiatric effects.