What are the side effects of Contrave (bupropion and naltrexone)?

Side Effects of Contrave (Bupropion and Naltrexone)

The most common side effects of Contrave (naltrexone/bupropion) include nausea, constipation, headache, vomiting, dizziness, insomnia, and dry mouth, with nausea being the most frequent adverse effect affecting up to 30% of patients. 1

Common Side Effects

The following side effects occur frequently in patients taking Contrave:

• Gastrointestinal effects:

  • Nausea (29.8%)
  • Constipation
  • Vomiting (0.7-2%)
  • Dry mouth

• Neurological effects:

  • Headache (0.9-1.8%)
  • Dizziness (0.7-1.4%)
  • Insomnia
  • Anxiety (0.6-5.4%)

• Other common effects:

  • Increased sweating
  • Tremor
  • Feeling jittery 1, 2

Serious Side Effects and Precautions

Contrave carries several important warnings that require careful consideration:

• Seizure risk: Bupropion can lower the seizure threshold. Contrave should be avoided in:

  • Patients with history of seizures
  • Anorexia or bulimia nervosa
  • Those abruptly discontinuing alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1

• Psychiatric effects:

  • Bupropion carries a black box warning for increased risk of suicidal thoughts in young adults within the first few months of treatment
  • May cause depression or precipitation of mania
  • Can cause agitation, anxiety, and irritability 1, 2

• Cardiovascular effects:

  • Can cause modest increases in blood pressure, especially in the first 8 weeks
  • May cause cardiac arrhythmias
  • Should be avoided in patients with uncontrolled hypertension 1

• Opioid interactions:

  • The naltrexone component blocks opioid receptors
  • Should be discontinued before procedures requiring opioid pain management
  • Can precipitate withdrawal in patients taking opioids 1

Discontinuation Rates

Approximately 25% of patients discontinue Contrave due to adverse effects compared to 10% with placebo. The most common reasons for discontinuation are:

• Nausea (4.6-9.6%)
• Vomiting (0.7-2%)
• Headache (0.9-1.8%)
• Dizziness (0.7-1.4%)
• Depression (0.2-0.6%) 1

Special Populations and Considerations

• Renal impairment:

  • For moderate to severe renal impairment: reduce dose to 1 tablet twice daily
  • Avoid in end-stage renal disease 1

• Hepatic impairment:

  • For moderate to severe hepatic impairment: limit to 1 tablet daily 1

• Pregnancy:

  • Contraindicated in pregnancy 1

• Patients with diabetes:

  • May provide modest improvements in glycemic control
  • Demonstrated a 0.6% reduction in HbA1c in clinical trials 1

Monitoring Recommendations

• Blood pressure: Monitor regularly, especially during the first 8 weeks
• Mental health: Watch for changes in mood, behavior, or suicidal thoughts
• Weight loss response: If <5% weight loss after 12 weeks at maintenance dose, consider discontinuation as patient is likely a poor responder 1

Drug Interactions

• Monoamine oxidase inhibitors (MAOIs): Contraindicated
• Opioids: Reduced efficacy of opioid analgesics
• CYP2B6 inhibitors/inducers: May affect bupropion levels
• Antihypertensive medications: May reduce efficacy of these medications 1

Contrave is generally not associated with increased risk of major adverse cardiovascular events compared to placebo based on available evidence, though initial blood pressure increases warrant monitoring 3.