Important Safety Information

Metformin is an antihyperglycemic drug used in the management of type 2 diabetes. Safety and efficacy for weight loss has not been established and it is NOT FDA-approved for weight management.

Bupropion is an aminoketone antidepressant and naltrexone is an opioid antagonist. The combination of the two medications sold under the brand name Contrave has been FDA-approved 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:

• 30 kg/m2 or greater (obese) or
• 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).

HOWEVER, the combination of these generic medications prescribed individually in alternative dosing regimens has NOT been FDA-approved for weight management.

IMPORTANT: This is a summary and does not have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

DO NOT TAKE METFORMIN IF YOU HAVE:

• Severe renal impairment (eGFR below 30 mL/minute/1.73 m2)
• Known allergy to metformin
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma

METFORMIN WARNINGS AND PRECAUTIONS

• Lactic Acidosis: See boxed warning below.
• Vitamin B-12 Deficiency: Metformin may lower vitamin B-12 levels. Measure hematological parameters annually and vitamin B-12 at 2 to 3 year intervals and manage any abnormalities.
• Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Lower dose of insulin or insulin secretagogue may be required.

METFORMIN SIDE EFFECTS: Most common adverse reactions (greater than or equal to 5%): hypoglycemia, diarrhea and nausea.

To report SUSPECTED ADVERSE REACTIONS, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

METFORMIN DRUG INTERACTIONS:

• Carbonic anhydrase inhibitors may increase risk of lactic acidosis. Consider more frequent monitoring.
• Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin. Consider the benefits and risks of concomitant use.
• Alcohol can potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake.

METFORMIN USE IN SPECIFIC POPULATIONS:

• Females and Males of Reproductive Potential: Advise premenopausal females of the potential or an unintended pregnancy.
• Geriatric Use: Assess renal function more frequently.
• Hepatic Impairment: Avoid use in patients with hepatic impairment.

DO NOT TAKE BUPROPION/NALTREXONE IF YOU HAVE:

• Uncontrolled hypertension
• Seizure disorders, anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
• Use of other bupropion-containing products
• Chronic opioid use
• During or within 14 days of taking monoamine oxidase inhibitors (MAOI)
• Known allergy to bupropion or naltrexone
• Pregnancy

BUPROPION/NALTREXONE SIDE EFFECTS: Most common adverse reactions (greater than or equal to 5%): nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea.

To report SUSPECTED ADVERSE REACTIONS, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

BUPROPION/NALTREXONE DRUG INTERACTIONS:

• 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 bupropion/naltrexone.
• Concomitant Treatment with CYP2B6 Inhibitors (e.g., ticlopidine or clopidogrel) can increase bupropion exposure. Do not exceed one tablet of bupropion twice daily when taken with CYP2B6 inhibitors.
• CYP2B6 Inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) may reduce efficacy by reducing bupropion exposure, avoid concomitant use.
• Drugs that Lower Seizure Threshold: Dose bupropion/naltrexone with caution.
• Dopaminergic Drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly with bupropion/naltrexone.
• Drug-Laboratory Test Interactions: Bupropion/naltrexone can cause false-positive urine test results for amphetamines.

BUPROPION/NALTREXONE USE IN SPECIFIC POPULATIONS:

• Pregnancy: Weight loss during pregnancy may cause fetal harm. Discontinue when a pregnancy is recognized.
• Nursing Mothers: Discontinue drug or nursing.
• Pediatric Use: Safety and effectiveness not established and use not recommended.