Bupropion and Naltrexone

CONTRAVE is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or overweight in the presence of at least one weight-related comorbid condition. CONTRAVE is a combination of naltrexone, an opioid antagonist, and bupropion, an aminoketone antidepressant, indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or overweight in the presence of at least one weight-related comorbid condition. Limitations of Use: The effect of CONTRAVE on cardiovascular morbidity and mortality has not been established. Coadministration with other naltrexone-containing products is not recommended.

CONTRAVE has two components: naltrexone, an opioid antagonist, and bupropion, a relatively weak inhibitor of the neuronal reuptake of dopamine and norepinephrine. Nonclinical studies suggest that naltrexone and bupropion have effects on two separate areas of the brain involved in the regulation of food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit (reward system). The exact neurochemical effects of CONTRAVE leading to weight loss are not fully understood.

CONTRAVE dose escalation schedule: Morning Dose Evening Dose Week 1 1 tablet None Week 2 1 tablet 1 tablet Week 3 2 tablets 1 tablet Week 4 – Onward 2 tablets 2 tablets

CONTRAVE is contraindicated in Uncontrolled hypertension Seizure disorder or a history of seizures Use of other bupropion-containing products (including, but not limited to, WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, APLENZIN and ZYBAN) Bulimia or anorexia nervosa, which increase the risk for seizure Chronic opioid or opiate agonist (e.g., methadone) or partial agonists (e.g., buprenorphine) use, or acute opiate withdrawal Patients undergoing an abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs Concomitant administration of monoamine oxidase inhibitors (MAOI).

Boxed warning (suicidal thoughts and behaviors warning: suicidal thoughts and behaviors): Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders. Monitor for worsening and emergence of suicidal thoughts and behaviors. CONTRAVE is not approved for use in pediatric patients. Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts. Discontinue CONTRAVE if symptoms develop. 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 other sections of the labeling: Suicidal Behavior and Ideation Neuropsychiatric Adverse Events Seizures Increase in Blood Pressure and Heart Rate Allergic Reactions Angle-Closure Glaucoma Most common adverse reactions (greater than or equal to 5%): nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea.

MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly. Drugs Metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of antidepressants, (e.g., selective serotonin reuptake inhibitors and many tricyclics), antipsychotics (e.g., haloperidol, risperidone and thioridazine), beta-blockers (e.g., metoprolol) and Type 1C antiarrhythmics (e.g., propafenone and flecainide). Consider dose reduction when using with CONTRAVE. Digoxin: May decrease plasma digoxin levels. Monitor digoxin levels. Concomitant Treatment with CYP2B6 Inhibitors (e.g., ticlopidine or clopidogrel) can increase bupropion exposure. Do not exceed one tablet twice daily when taken with CYP2B6 inhibitors.

Store at 25°C (77°F), excursions permitted to 15° to 30°C (59° to 86°F).