Usual Adult Dose for Weight Loss

Each extended-release tablet contains naltrexone 8 mg/bupropion 90 mg:

Initial dose:

• Week 1: One tablet orally once a day in the morning
• Week 2: One tablet orally 2 times a day (morning and evening)
• Week 3: Two tablets orally in the morning and 1 tablet orally in the evening
• Week 4: Two tablets orally 2 times a day (morning and evening)

Maintenance dose: 2 tablets orally 2 times a day (morning and evening)
Maximum dose: 4 tablets/day (naltrexone 32 mg/bupropion 360 mg)

Comments:

• Therapy should be discontinued if a patient has not lost at least 5% of baseline body weight after 12 weeks at maintenance dose as it is unlikely that clinically meaningful weight loss will occur with continued treatment.
• The effect of this drug on cardiovascular morbidity and mortality has not been established.
• The safety and effectiveness of this drug in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established.

Uses: 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 comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).

Renal Dose Adjustments

Mild renal impairment: No adjustment recommended
Moderate renal impairment: Maximum dose: 1 tablet orally 2 times a day (morning and evening)
Severe renal impairment: Maximum dose: 1 tablet orally 2 times a day (morning and evening)
ESRD: Not recommended

Liver Dose Adjustments

Mild hepatic impairment: No adjustment recommended
Moderate hepatic impairment: Maximum dose: 1 tablet orally 2 times a day (morning and evening)
Severe hepatic impairment: Not recommended

Dose Adjustments

Elderly: Use caution; elderly patients are more likely to have impaired renal function, therefore, consider monitoring renal function

Concomitant Use of MAOIs: Contraindicated

• Allow at least 14 days between discontinuation of an MAOI and initiating therapy with this drug; conversely, allow at least 14 days after stopping this drug before initiating an MAOI

Concomitant Use with CYP450 2B6 Inhibitors:

• Maximum dose: 1 tablet orally 2 times a day (morning and evening)

Avoid Concomitant Use with CYP450 2B6 Inducers

Precautions

US BOXED WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

• Suicidality and Antidepressant Drugs: This drug is not approved for use in the treatment of major depressive disorder or other psychiatric disorders. The drug contains bupropion, the same active ingredient in some antidepressant medications. Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects over age 24 years and there was a reduction in risk with antidepressant use in subjects aged 65 and older. In patients of all ages who start therapy, monitor closely for worsening, and for the emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. This drug is not approved for use in pediatric patients.

CONTRAINDICATIONS:

• Uncontrolled hypertension
• Seizure disorder or a history of seizures
• Concomitant use of other bupropion-containing products
• Bulimia or anorexia nervosa, which increase the risk for seizure
• Chronic opioid or opiate agonist or partial agonists use, or acute opiate withdrawal
• Patients undergoing an abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
• Concomitant, or use within 14 days of monoamine oxidase inhibitors (MAOI) including linezolid or IV methylene blue
• Known allergy to active substance or any product excipient; anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported with bupropion

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

ESRD: Not recommended

Other Comments

Administration advice:

• Take orally twice a day
• Swallow whole; do not cut, chew, or crush tablets
• Follow dose escalation schedule; do not take more than 2 tablets at any one time
• May take with food, but should not be taken with high-fat meals as it may increase exposure to the drug

Missed dose: If a dose is missed, do not take an additional dose, but take the prescribed next dose at the usual time

General:

• It is unlikely that patients who do not respond with at least a 5% loss of baseline body weight after 12 weeks at the maintenance dose, will achieve and sustain clinically meaningful weight loss with continued use, therefore, discontinuation is recommended.
• This drug should not be used in opioid dependent patients due to the possibility of precipitating opioid withdrawal; an opioid free interval of 7 to 10 days is recommended for patients on short-acting opioids while an opioid free interval of up to 2 weeks may be needed for those on buprenorphine or methadone.

Monitoring:

• Measure blood pressure and pulse prior to starting therapy and at regular intervals, particularly among patients with controlled hypertension.
• Measure blood glucose levels prior to and during treatment in patients with type 2 diabetes.
• Monitor patients closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months and with any change in dose.
• Prior to treatment initiation, screen patients for a history of/risk factors for bipolar disorder.

Patient Advice:

• Patients should be instructed to read the US FDA-approved Medication Guide.
• Patients should be instructed to follow the dose escalation schedule and not to take more than the recommended dose.
• Patients should understand that this drug contains an opioid antagonist and therefore should not be taken with opioid medications.
• Patients, families and caregivers should understand changes in behavior and mood may occur; their healthcare provider should be contacted promptly for any new or sudden changes in mood, behavior, thoughts, or feelings.
• Patients should discuss alcohol use with their healthcare provider; patients should avoid or minimize alcohol use and should avoid suddenly stopping alcohol if they drink a lot as this may increase the risk of having a seizure.
• Women of child bearing potential should discuss use of this drug with their healthcare provider; if a patient becomes pregnant, this drug should be discontinued.

Frequently asked questions

• Does naltrexone cause weight gain?