Indicated for:

Major Depressive Disorder:

• The treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM).

The efficacy of the immediate-release formulation of bupropion was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult patients with MDD. The efficacy of the sustained-release formulation of bupropion in the maintenance treatment of MDD was established in a long-term (up to 44 weeks), placebo-controlled trial in patients who had responded to bupropion in an 8 week study of acute treatment.

Seasonal Affective Disorder:

• The prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD).

For the prevention of seasonal MDD episodes associated with SAD, initiate APLENZIN in the autumn, prior to the onset of depressive symptoms. Continue treatment through the winter season. Taper and discontinue APLENZIN in early spring. For patients treated with 348 mg per day, decrease the dose to 150 mg once daily before discontinuing APLENZIN. Individualize the timing of initiation and duration of treatment should be individualized, based on the patient’s historical pattern of seasonal MDD episodes.

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants. Monitor for worsening and emergence of suicidal thoughts and behaviors. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Serious neuropsychiatric adverse events have been reported in patients taking bupropion for smoking cessation. These postmarketing reports 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.

APLENZIN is contraindicated in patients with the following conditions:

• In patients with a seizure disorder
• 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 APLENZIN 
• In patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
• The use of MAOIs (intended to treat psychiatric disorders) concomitantly with APLENZIN or within 14 days of discontinuing treatment with APLENZIN is contraindicated. There is an increased risk of hypertensive reaction when APLENZIN is used concomitantly with MAOIs
• The use of APLENZIN within 14 days of discontinuing treatment with an MAOI is also contraindicated. Starting APLENZIN in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated

Anaphylactoid/anaphylactic reactions and Stevens-Johnson Syndrome have been reported.

APLENZIN can cause seizures. The risk of seizure is dose-related. The dose should not exceed 522 mg once daily.

To minimize the risk of seizure, increase the dose gradually.

In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose is 174 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing.

Consider reducing the dose and/or frequency of APLENZIN in patients with renal impairment (glomerular filtration rate less than 90 mL/min).

Treatment with APLENZIN can result in elevated blood pressure and hypertension. Assess blood pressure before initiating treatment with APLENZIN, and monitor periodically during treatment.

There are no controlled studies assessing the safety of bupropion in patients with a recent history of myocardial infarction or unstable cardiac disease.

Antidepressant treatment can precipitate a manic, mixed, or hypomanic manic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. APLENZIN is not approved for the treatment of bipolar depression.

Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease. Some patients experienced worsening of their psychiatric illnesses.

The pupillary dilation that occurs following use of many antidepressant drugs including APLENZIN may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with APLENZIN. Conversely, at least 14 days should be allowed after stopping APLENZIN before starting an MAOI antidepressant.

Do not start APLENZIN in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue.

The consumption of alcohol during treatment with APLENZIN should be minimized or avoided.

Co-administration of APLENZIN with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g., haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, and flecainide). When used concomitantly with APLENZIN, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.

Drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen), theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Patients treated concomitantly with APLENZIN and such drugs may require increased doses of the drug.

Concomitant treatment with ritonavir, lopinavir, and efavirenz: can decrease bupropion and hydroxybupropion exposure.

Use with carbamazepine, phenobarbital, and phenytoin may induce metabolism of bupropion and may decrease bupropion exposure.

Use extreme caution when co-administering APLENZIN with other drugs that lower the seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids).

CNS toxicity has been reported when bupropion was co-administered with levodopa or amantadine.

False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion.

Increased risk for ventricular septal defect following first trimester maternal bupropion exposure.

Bupropion and its metabolites are present in human milk.

GoToSource

• Use in patients under the age of 18. GoToSource

• Attention deficit hyperactivity disorder, bipolar disorder, weight loss and social phobia. GoToSource

• Female hypoactive sexual desire disorder. GoToSource

• Binge eating disorder. GoToSource

• Restless legs syndrome. GoToSource

• Neuropathic pain. GoToSource

• Panic disorder and parkinson’s disease. GoToSource

• Smoking cessation. GoToSource

• Schizophrenic disorders. GoToSource

Thrombotic thrombocytopenic purpura syndrome (blood clots form in small blood vessels in the body). GoToSource

Hip fractures. GoToSource

Insomnia. GoToSource

Acute agitated delirium. GoToSource

Mania or hypomania. GoToSource

Aphthous ulcers (mouth ulcers). GoToSource

Cardiac conduction disturbances. GoToSource

Severe constipation. GoToSource

Increased the risk of suicidal thinking and behavior (suicidality). GoToSource

Seizures. GoToSource

Birth defects. GoToSource 

Angle-closure glaucoma. GoToSource

Lawsuits filed for birth defects.