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IMPORTANT SAFETY INFORMATION
Use in Treating Psychiatric Disorders:
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short‐term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of APLENZIN or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. APLENZIN is not approved for use in pediatric patients.

Use in Smoking Cessation Treatment:
APLENZIN is not approved for smoking cessation treatment, but bupropion under the name of ZYBAN® is approved for this use. Serious neuropsychiatric events, including but not limited to depression, suicidal ideation, suicide attempt, and completed suicide have been reported in patients taking bupropion for smoking cessation.
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IMPORTANT SAFETY INFORMATION
Use in Treating Psychiatric Disorders:
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of APLENZIN or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. APLENZIN is not approved for use in pediatric patients.

Use in Smoking Cessation Treatment:
APLENZIN is not approved for smoking cessation treatment, but bupropion under the name of ZYBAN® is approved for this use. Serious neuropsychiatric events, including but not limited to depression, suicidal ideation, suicide attempt, and completed suicide have been reported in patients taking bupropion for smoking cessation.

APLENZIN is contraindicated in patients who have a seizure disorder, patients being treated with ZYBAN® (bupropion HCl) Sustained-Release Tablets, WELLBUTRIN® (bupropion HCl), WELLBUTRIN SR® (bupropion HCl) Sustained-Release Tablets, or any other medications that contain bupropion, patients who have or had bulimia or anorexia nervosa, patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines), patients who have shown an allergic response to bupropion and patients taking MAO inhibitors. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of APLENZIN.

Physicians should be aware that bupropion is associated with a risk of seizure, which is dose related. The incidence of seizure may be similar to that of the sustained-release formulations of bupropion, since APLENZIN has demonstrated bioequivalence. To reduce the risk of seizures, please see WARNINGS and PRECAUTIONS in the Prescribing Information for patient selection considerations, including concomitant medications and dosing recommendations.

Physicians, families, and caregivers should monitor patients for suicidality as well as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, and other unusual changes in behavior. All patients should be closely monitored for these symptoms, especially at the beginning of therapy, or with changes in dose and reported immediately to the patient’s healthcare provider. Please consult prescribing information for APLENZIN for additional monitoring recommendations. There is concern that such symptoms may be precursors to suicidality, although a causal link has not been proven. If such symptoms occur, prescribers should consider changing or discontinuing treatment. Patients should be screened for bipolar disorder prior to initiating treatment with an antidepressant.

APLENZIN is not approved for smoking cessation treatment, but bupropion under the name ZYBAN is approved for this use. Serious neuropsychiatric symptoms have been reported in patients taking bupropion for smoking cessation. Some reported cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking. These events have occurred in patients with and without pre-existing psychiatric disease; some have experienced worsening of their psychiatric illnesses. All patients being treated with bupropion as part of smoking cessation treatment should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness.

Advise patients and caregivers that the patient using bupropion for smoking cessation should stop taking bupropion and contact a healthcare provider immediately if agitation, hostility, depressed mood, or changes in thinking or behavior that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. In many post-marketing cases, resolution of symptoms after discontinuation of ZYBAN was reported, although in some cases the symptoms persisted; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

Antidepressants can precipitate manic episodes in bipolar disorder patients during the depressed phase of their illness and may activate latent psychosis in other susceptible patients. APLENZIN is expected to pose similar risks.

When treating patients with severe hepatic cirrhosis, extreme caution should be exercised, and a reduced dosage and/or frequency is required to avoid accumulation. Increased restlessness, agitation, anxiety, and insomnia, especially shortly after initiation of treatment, have been associated with treatment with bupropion. Neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion have been reported with bupropion. Anaphylactoid reactions characterized by symptoms such as pruritus, urticaria, angioedema, and dyspnea requiring medical treatment have been reported in clinical trials with bupropion. There have been reports of hypertension, in some cases severe, in patients receiving bupropion alone and in combination with nicotine replacement therapy.

Co-administration with drugs that are metabolized by CYP2B6 or CYP2D6 isoenzymes should be approached with caution. Please see the DRUG INTERACTIONS section in the Prescribing Information for further information.

The most common adverse reactions reported are anorexia, dry mouth, rash, sweating, tinnitus, tremor, abdominal pain, agitation, anxiety, dizziness, insomnia, myalgia, nausea, palpitation, pharyngitis, and urinary frequency.

Please click here for full Prescribing Information, including boxed WARNING.
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