IMPORTANT CHANGES January 8, 2016

ALL ContraveComplete Card claims must be processed
against insurance or they will be rejected. If patients have
no insurance, pharmacists must call McKesson to receive

Please see Important Safety Information, including complete warnings for
suicidal thoughts and behaviors and neuropsychiatric reactions below.

*Must meet Eligibility Requirements. Some restrictions apply. For Eligibility Requirements and Terms & Conditions, please visit www.Contrave.com/FAQ.

Indication
CONTRAVE is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of:

Contraindications
CONTRAVE is contraindicated in: uncontrolled hypertension; seizure disorder or a history of seizures; use of other bupropion-containing products; bulimia or anorexia nervosa, which increase the risk for seizure; chronic opioid or opiate agonist (eg, methadone) or partial agonists (eg, buprenorphine) use, or acute opiate withdrawal; patients undergoing an abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs; use during/within 14 days following treatment with monoamine oxidase inhibitors (MAOIs)—there is an increased risk of hypertensive reactions when CONTRAVE is used concomitantly with MAOIs and use with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated; known allergy to any component of CONTRAVE—anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported; pregnancy.

WARNINGS AND PRECAUTIONS

Suicidal Behavior and Ideation
All patients being treated with antidepressants for any indication should be monitored for clinical worsening, suicidality, and unusual changes in behavior, especially during initial months of therapy, or at times of dose changes.

Consider changing the therapeutic regimen or discontinuing the medication in patients with persistently worse or emergent symptoms of depression or suicidality especially if severe or abrupt in onset.

Families and caregivers of patients being treated with antidepressants for any reason should be alerted to monitor patients’ emergence of suicidality, anxiety, agitation, irritability, unusual changes in behavior, and other symptoms daily, and immediately report such symptoms to healthcare providers.

Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment
Serious neuropsychiatric symptoms have been reported in patients taking bupropion for smoking cessation, including changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, panic, suicidal ideation, suicide attempt, and completed suicide. Observe patients for neuropsychiatric reactions and instruct patients to contact a healthcare professional.

Seizures
The risk of seizure is dose-related. Discontinue treatment and do not restart CONTRAVE in patients who experience a seizure. Use caution when prescribing CONTRAVE to patients with risk factors for seizure, including: history of head trauma or prior seizure, severe stroke, arteriovenous malformation, central nervous system tumor or infection, or metabolic disorders (eg, hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia); excessive use of alcohol or sedatives, addiction to cocaine or stimulants, or withdrawal from sedatives; patients with diabetes treated with insulin and/or oral diabetic medications (sulfonylureas and meglitinides) that may cause hypoglycemia; concomitant administration of medications that may lower the seizure threshold, including other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, systemic steroids. Risk of seizure may be minimized by adhering to the dosing recommendations, in particular: do not exceed 360 mg of the bupropion component daily; administer twice daily; escalate the dose gradually; take no more than two tablets at one time; avoid administering with high-fat meals; wait until the next scheduled dose to resume the regular dosing schedule if a dose is missed.

Patients Receiving Opioid Analgesics
Vulnerability to Opioid Overdose. CONTRAVE should not be administered to patients receiving chronic opioids. If chronic opiate therapy is required, CONTRAVE treatment should be stopped. In patients requiring intermittent opiate treatment, CONTRAVE therapy should be temporarily discontinued and lower doses of opioids may be needed. Patients should be alerted that they may be more sensitive to opioids, even at lower doses, after CONTRAVE treatment is discontinued. Patients should be told any attempt to overcome naltrexone opioid blockade by administering large amounts of exogenous opioids may lead to a fatal overdose or life-threatening opioid intoxication (eg, respiratory arrest, circulatory collapse).

Precipitated Opioid Withdrawal. An opioid-free interval of at least 7 to 10 days is recommended for patients previously dependent on short-acting opioids; those transitioning from buprenorphine or methadone may need as long as two weeks. Patients should be made aware of the risks and encouraged to accurately report last opioid use.

Increase in Blood Pressure (BP) and Heart Rate (HR)
CONTRAVE can cause an increase in systolic BP, diastolic BP, and/or resting HR. Hypertension, in some cases severe and requiring acute treatment, has been reported with other bupropion-containing products. Measure BP and pulse prior to starting CONTRAVE and monitor regularly, particularly among patients with cardiac or cerebrovascular disease and/or with controlled hypertension prior to treatment.

Allergic Reactions
Anaphylactoid/anaphylactic reactions and symptoms of delayed hypersensitivity, rare spontaneous reports of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock have been reported with bupropion. Patients should discontinue CONTRAVE and consult a healthcare provider if they develop an allergic or anaphylactoid/anaphylactic reaction.

Hepatotoxicity
Cases of hepatitis, clinically significant liver dysfunction, and transient asymptomatic transaminase elevations have been observed with naltrexone exposure. Warn patients of the risk of hepatic injury and advise them to discontinue CONTRAVE and seek medical attention if they experience signs/symptoms of acute hepatitis.

Activation of Mania
Bupropion treatment can precipitate a manic, mixed, or hypomanic episode, especially in patients with bipolar disorder or risk factors for bipolar disorder. Before initiating CONTRAVE, screen patients for risk factors and history of bipolar disorder. CONTRAVE is not approved for use in treating bipolar depression.

Angle-Closure Glaucoma
Pupillary dilation that occurs following use of many antidepressants, including bupropion, may trigger an angle-closure attack in patients with anatomically narrow angles who do not have a patent iridectomy.

Hypoglycemia With Use of Antidiabetic Medications
Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues (eg, sulfonylureas). Measure blood glucose levels prior to and during CONTRAVE treatment. Consider decreasing doses for non-glucose-dependent antidiabetic medications to mitigate the risk of hypoglycemia.

Adverse Reactions
Most common adverse reactions (≥5%) include: nausea (32.5%), constipation (19.2%), headache (17.6%), vomiting (10.7%), dizziness (9.9%), insomnia (9.2%), dry mouth (8.1%), and diarrhea (7.1%).

Drug Interactions
Do not use with MAOIs or CYP2B6 inducers. Use caution and consider dose reduction of drugs metabolized by CYP2D6. Reduce CONTRAVE dose when taken with CYP2B6 inhibitors. Dose with caution when used with drugs that lower seizure threshold. Use caution and monitor for CNS toxicity when using with dopaminergic drugs (levodopa and amantadine). CONTRAVE can cause false positive urine test results for amphetamines.

Please see accompanying Full Prescribing Information and Medication Guide for CONTRAVE.

CONTRAVE^® is a trademark of Orexigen Therapeutics, Inc. registered with the U.S. Patent and Trademark Office and used under license by Takeda Pharmaceuticals America, Inc.

All other trademarks are the property of their respective owners.

To learn more about Contrave, please visit www.ContraveHCP.com

	USD/BPN/15/0206                     1/16
©2016 Takeda Pharmaceuticals U.S.A., Inc.