Can an adult with a BMI ≥30 kg/m² (or ≥27 kg/m² with hypertension, type 2 diabetes, or dyslipidemia) and no history of seizure disorder, uncontrolled hypertension, eating disorder, chronic opioid use, or pregnancy safely start Contrave (naltrexone/bupropion) for weight loss, and what is the recommended titration schedule and monitoring?

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Last updated: February 27, 2026 • View editorial policy

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Contrave for Weight Loss: Eligibility, Titration, and Monitoring

Direct Recommendation

An adult with BMI ≥30 kg/m² (or ≥27 kg/m² with weight-related comorbidities) who meets all safety criteria can safely start Contrave using a 4-week titration schedule, with mandatory blood pressure monitoring and a 12-week efficacy checkpoint. 1, 2

Patient Eligibility Criteria

FDA-Approved Indications

  • BMI ≥30 kg/m² (obese), OR 1, 3
  • BMI ≥27 kg/m² (overweight) with at least one weight-related comorbidity: 1, 3
    • Type 2 diabetes mellitus
    • Hypertension
    • Dyslipidemia

Absolute Contraindications (Must Screen Before Prescribing)

Neurologic/Psychiatric:

  • History of seizure disorder or any condition predisposing to seizures (e.g., head trauma, brain tumor, stroke, epilepsy) 1, 2
  • Eating disorders (anorexia nervosa or bulimia nervosa) 1
  • Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1, 4

Cardiovascular:

  • Uncontrolled hypertension (≥140/90 mm Hg or ≥130/80 mm Hg in high-risk patients) 1, 5, 2

Medication-Related:

  • Current or recent (within 14 days) use of monoamine oxidase inhibitors (MAOIs) 1, 4
  • Chronic opioid use or opioid dependence (naltrexone component will precipitate severe withdrawal) 1, 5, 2

Pregnancy/Reproductive:

  • Pregnancy or women who may become pregnant without reliable contraception 1, 2
  • Breastfeeding (bupropion is present in breast milk; case reports of seizures in breastfed infants exist) 4

Organ Impairment:

  • End-stage renal disease or severe renal impairment 4, 2
  • Moderate to severe hepatic impairment (requires dose adjustment, not absolute contraindication) 4, 2

Standard Titration Schedule

The 4-week titration protocol minimizes nausea and seizure risk while achieving therapeutic dosing: 1, 2

Week Morning Dose Evening Dose Total Daily Dose
Week 1 1 tablet (8/90 mg) None 8 mg naltrexone / 90 mg bupropion
Week 2 1 tablet (8/90 mg) 1 tablet (8/90 mg) 16 mg naltrexone / 180 mg bupropion
Week 3 2 tablets (16/180 mg) 1 tablet (8/90 mg) 24 mg naltrexone / 270 mg bupropion
Week 4+ 2 tablets (16/180 mg) 2 tablets (16/180 mg) 32 mg naltrexone / 360 mg bupropion (maintenance)

Critical timing consideration: Administer the second daily dose before 3 PM to minimize insomnia risk. 4, 5, 2

Maximum dose: Never exceed 32 mg naltrexone / 360 mg bupropion daily (4 tablets total); higher doses markedly increase seizure risk above 0.1%. 1, 4, 5, 2

Dose Adjustments for Special Populations

Moderate to Severe Renal Impairment (eGFR <90 mL/min)

  • Reduce total daily dose by 50% (maximum 1 tablet twice daily = 16 mg naltrexone / 180 mg bupropion daily) 4, 2
  • Bupropion and its metabolites accumulate renally; standard dosing risks toxicity 4

Moderate to Severe Hepatic Impairment

  • Maximum dose: 1 tablet once daily (8 mg naltrexone / 90 mg bupropion) 4, 2
  • Both naltrexone and bupropion undergo hepatic metabolism 4

Older Adults (≥65 years)

  • Start at standard titration schedule but monitor closely for adverse effects 4
  • Consider lower maintenance dose if tolerability issues arise 4

Mandatory Monitoring Protocol

Baseline Assessment (Before Initiation)

  • Blood pressure and heart rate (must be controlled; uncontrolled hypertension is contraindication) 1, 5, 2
  • Mental status examination focusing on suicidal ideation, especially in patients <24 years 1, 4, 2
  • Confirm patient is not taking opioid medications (naltrexone component contraindicated) 5, 2
  • Screen for seizure history and conditions predisposing to seizures 1, 5, 2
  • Pregnancy test in women of childbearing potential 1, 2

Weeks 1–2 (High-Risk Period)

  • Weekly assessment for: 4, 5, 2
    • Suicidal ideation, agitation, irritability, behavioral changes (black box warning for patients <24 years)
    • Early signs of serotonin syndrome (confusion, tremor, clonus, hypertension, tachycardia, sweating)
    • Seizure warning signs (aura, confusion, muscle twitching)
  • Blood pressure and heart rate at least weekly 5, 2

First 12 Weeks

  • Blood pressure and heart rate monitoring periodically (transient increases of ~1.5 mm Hg may occur) 1, 2
  • Neuropsychiatric symptom surveillance (depression, anxiety, mood changes) 1, 2, 6

12-Week Efficacy Checkpoint (Mandatory)

  • Discontinue Contrave if weight loss is <5% of baseline body weight 1, 2
  • This is an FDA-mandated efficacy threshold; continuing beyond 12 weeks without adequate response is not recommended 1, 2

Ongoing Monitoring

  • Periodic blood pressure and heart rate checks throughout treatment 1, 2
  • Mental health assessment for mood changes, suicidal ideation 1, 4, 2

Expected Weight Loss Outcomes

Clinical Trial Results

  • Average weight loss: 5–9 kg (11–22 lbs) over 56 weeks compared to placebo 7, 3
  • Proportion achieving ≥5% weight loss: 44.5–48% (vs. 16–18.9% with placebo) 1, 3
  • Proportion achieving ≥10% weight loss: Significantly higher than placebo 3
  • Patients with type 2 diabetes: 0.6% reduction in hemoglobin A1c (vs. 0.1% with placebo) 1

Cardiometabolic Benefits

  • Significant improvements in triglycerides, HDL cholesterol, fasting glucose, and blood pressure (beyond weight loss alone) 1, 7, 3
  • No increased risk of major adverse cardiovascular events (MACE) in systematic review of 70 studies 8

Common Side Effects and Management

Most Frequent Adverse Events

  • Nausea (most common; managed by slow titration) 1, 6, 3
  • Constipation 1, 6
  • Headache 1
  • Dizziness 1, 6
  • Insomnia (minimize by dosing second tablet before 3 PM) 1, 4, 5
  • Dry mouth 1

Serious Adverse Events (Rare but Important)

  • Seizures: ~0.1% (1 in 1,000) at maximum approved dose 1, 4
  • Neuropsychiatric disorders: Depression, anxiety, suicidal ideation (black box warning for patients <24 years) 1, 4, 6
  • Hypertension and tachycardia: Monitor blood pressure regularly 1, 6
  • Allergic reactions: Including Stevens-Johnson syndrome (rare) 6

Tolerability Strategy

  • Slow dose titration over 4 weeks minimizes nausea and other GI side effects 1, 2
  • If intolerable side effects occur: Reduce to previous tolerable dose and maintain for 1–2 weeks before resuming titration 5

Critical Safety Pitfalls to Avoid

  1. Do not exceed 32 mg naltrexone / 360 mg bupropion daily (seizure risk increases markedly) 1, 4, 5, 2
  2. Do not skip intensive monitoring during weeks 1–2 (highest risk for suicidal ideation and serotonin syndrome) 4, 5, 2
  3. Do not continue beyond 12 weeks without ≥5% weight loss (FDA efficacy threshold) 1, 2
  4. Do not administer second dose after 3 PM (insomnia risk) 4, 5, 2
  5. Do not prescribe to patients on chronic opioids (naltrexone precipitates severe withdrawal) 1, 5, 2
  6. Do not use in uncontrolled hypertension (both components elevate blood pressure) 1, 5, 2

Ideal Candidate Profile

Contrave may be particularly beneficial for patients who: 1

  • Have concomitant depression (bupropion component treats both conditions)
  • Are trying to quit smoking or reduce alcohol intake
  • Describe food cravings or addictive eating behaviors
  • Prefer a non-controlled substance (unlike phentermine)
  • Prefer an oral medication (unlike liraglutide or semaglutide injectables)

Alternative FDA-Approved Weight-Loss Options (If Contrave Contraindicated)

Medication Typical Dose Key Advantage
Liraglutide 3.0 mg (Saxenda) 3.0 mg SC daily No seizure risk; safe with opioids [1,5]
Semaglutide 2.4 mg (Wegovy) 2.4 mg SC weekly Superior weight loss (~12–15%); no seizure risk [1]
Orlistat (Xenical) 120 mg PO TID with meals No drug interactions; no CNS effects [5]
Phentermine/topiramate ER (Qsymia) 7.5/46 mg to 15/92 mg daily Greater weight loss than Contrave; controlled substance [1]

Note: Phentermine/topiramate ER should be avoided in patients on antiepileptic drugs or with seizure history due to topiramate interactions. 5

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Contrave Naltrexone Dosage Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

4
Guideline

Bupropion Dosing and Administration

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

5
Guideline

Safety Assessment for Adding Contrave (Naltrexone/Bupropion) to Complex Medication Regimens

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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