Is Contrave (bupropion and naltrexone) safe for weight loss in a patient with a history of thyroid cancer?

Contrave Use in Thyroid Cancer Patients

Contrave (naltrexone/bupropion) is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, but this contraindication applies specifically to liraglutide (Saxenda), not to Contrave itself. Based on the available evidence, Contrave does not carry a specific thyroid cancer contraindication and can be considered for weight loss in patients with a history of thyroid cancer, provided other contraindications are absent. 1

Key Safety Considerations for Contrave

Absolute Contraindications to Screen For

Before prescribing Contrave to any patient, including those with thyroid cancer history, verify the following are NOT present:

• Uncontrolled hypertension - Contrave can elevate blood pressure and heart rate, making this an absolute contraindication 1, 2
• Seizure disorders or conditions predisposing to seizures - The bupropion component lowers seizure threshold; maximum dose must not exceed 32 mg naltrexone/360 mg bupropion daily to maintain seizure risk at 0.1% 1, 2
• Current opioid use - Naltrexone is an opioid antagonist and will precipitate severe withdrawal 1, 2
• Eating disorders (bulimia or anorexia nervosa) - Increased seizure risk 1, 2
• Pregnancy or inadequate contraception - Teratogenic effects cannot be ruled out 1, 3
• MAOI use within 14 days - Risk of hypertensive crisis 1
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs - Dramatically increases seizure risk 2

Relative Contraindications Requiring Dose Adjustment

• Moderate to severe hepatic impairment - Maximum dose 150 mg daily (one tablet) 1, 2
• Moderate to severe renal impairment - Reduce total daily dose by 50% 1, 2

Dosing Protocol for Contrave

The American Gastroenterological Association recommends a specific titration schedule to minimize adverse effects: 1

• Week 1: 8 mg naltrexone/90 mg bupropion once daily in the morning 1
• Week 2: 8/90 mg twice daily 1
• Week 3: 16 mg naltrexone/180 mg bupropion in the morning, 8/90 mg in the evening 1
• Week 4 and beyond: 16/180 mg twice daily (maintenance dose) 1

The second dose should be taken before 3 PM to minimize insomnia risk. 2

Efficacy and Expected Outcomes

• Contrave produces 5.0-9.3% weight loss over 56 weeks, with placebo-subtracted weight loss of 3.2-5.2% 4
• 45-66% of patients achieve ≥5% weight loss, with placebo-subtracted proportion of 23-34% 4
• Average weight loss across four Phase III trials was approximately 11-22 lbs (5-9 kg) 5
• Discontinue if <5% weight loss at 12 weeks and consider alternative treatments 1

Monitoring Requirements

Baseline Assessment

• Blood pressure and heart rate measurement 1, 2
• Mental status examination focusing on suicidal ideation, particularly in patients <24 years old 2
• Confirm patient is not taking opioid medications 2

Ongoing Monitoring

• Blood pressure and heart rate monitoring - Especially during first 12 weeks, as Contrave can cause elevations 1, 2
• Monthly assessment for first 3 months, then at least every 3 months 1
• Neuropsychiatric monitoring - Watch for aggressiveness, depression, suicidal ideation, anxiety, sleep disorders, and psychotic symptoms 2, 3
• Efficacy assessment at 12 weeks - If inadequate weight loss, discontinue 1

Common Adverse Effects

• Gastrointestinal: Nausea (most common), constipation, vomiting - affects approximately 50% of patients 1, 3, 4
• Neuropsychiatric: Headache, dizziness, insomnia, anxiety 1, 4
• Cardiovascular: Small increase in heart rate, potential blood pressure elevation 3, 4

Serious Adverse Effects (Rare)

• Seizures - Risk approximately 0.1% at recommended doses 2, 4
• Suicidal thoughts - Black box warning, especially in patients <24 years old 2
• Severe neuropsychiatric disorders - Cognitive impairment, psychotic symptoms 3
• Cardiac arrhythmias - Excess noted in clinical trials 3
• Stevens-Johnson syndrome - Rare allergic reaction 3

Clinical Context: Thyroid Cancer Specifics

The confusion regarding thyroid cancer contraindication stems from liraglutide (Saxenda), which carries a black box warning for medullary thyroid carcinoma and MEN 2. 1 This contraindication does NOT apply to Contrave. The guideline evidence clearly differentiates these medications, listing liraglutide's thyroid contraindication separately from Contrave's contraindications. 1

Critical Pitfalls to Avoid

• Do not confuse Contrave with liraglutide - Only liraglutide has thyroid cancer contraindications 1
• Do not exceed maximum dose - Seizure risk increases significantly above 32/360 mg daily 1, 2
• Do not prescribe with concurrent opioid therapy - This will precipitate withdrawal 1, 2
• Do not ignore blood pressure monitoring - Uncontrolled hypertension is an absolute contraindication and can worsen on therapy 1, 2
• Do not continue beyond 12 weeks without adequate response - Discontinue if <5% weight loss 1

Evidence Quality Note

While the guideline evidence 1 provides comprehensive safety information and clearly distinguishes between different weight loss medications, the research evidence 3 raises concerns about the modest weight loss benefit (only a few additional kilograms) relative to the risk profile. However, the guideline evidence from the American Gastroenterological Association represents the current standard of care for prescribing these medications. 1