NALTREXONE–BUPROPION

Class

• Neuroscience-based Nomenclature: opioid receptor antagonist and dopamine reuptake inhibitor and releaser
• Opioid antagonist combined with a norepinephrine and dopamine reuptake inhibitor; weight management medication

NALTREXONE–BUPROPION commonly prescribed for

(Bold for FDA approved)

How NALTREXONE–BUPROPION works

• Bupropion increases dopamine and norepinephrine by blocking both the dopamine and the norepinephrine transporters. In the hypothalamus, these 2 neurotransmitters activate POMC neurons, causing the release of POMC. POMC is then broken down into alpha-melanocyte- stimulating hormone, which binds to melanocortin 4 receptors to suppress appetite. However, stimulation of POMC neurons also activates an endogenous opioid-mediated negative feedback loop, which mitigates the appetite-suppressing effects.

• Naltrexone can block mu opioid receptors, thus preventing opioid-mediated negative feedback. Such an action would synergize with simultaneous activation of the appetite- suppressing pathway by bupropion. This results in more robust and long-lasting appetite suppression than with either drug alone.

How long until NALTREXONE–BUPROPION works

• At least 5% weight loss is generally achieved after 12 weeks on maximum daily dose

Notable Side Effects

• Nausea, constipation, vomiting, diarrhea, dry mouth

• Headache, dizziness, insomnia

Life Threatening Side Effects

• Increased blood pressure or heart rate

• Rare seizures (risk increases with doses above the recommended maximums; risk increases for patients with predisposing factors)

• Hepatocellular injury (at excessive doses)

• Rare induction of mania

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

• Effect on cardiovascular morbidity and mortality has not been established

weight gain

unusual

sedation

unusual

What to do about NALTREXONE–BUPROPION side effects

• Wait

• In a few weeks, switch to another agent

usual dosage range

• 16 mg naltrexone/180 mg bupropion twice per day

Dosage Forms

• Extended-release tablet (naltrexone/ bupropion) 8 mg/90 mg

long term use

• Has been evaluated in controlled studies up to 56 weeks

habit forming

• No

Renal Impairment

• Maximum dose is 8 mg/90 mg twice per day in patients with moderate to severe impairment

• Not studied or recommended for use in patients with end-stage renal disease

Hepatic Impairment

• Dose adjustment not necessary in patients with mild impairment

• Maximum dose is 8 mg/90 mg twice per day in patients with moderate impairment

• Not recommended for use in patients with severe hepatic impairment

Cardiac Impairment

• Not systematically evaluated in patients with cardiac impairment

• Measure blood pressure and heart rate before and during treatment

Elderly

• Some patients may tolerate lower doses better

Children and Adolescents

• Safety and efficacy have not been established

• Not recommended for use in children or adolescents

Pregnancy

• Contraindicated

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended to discontinue drug or formula feed