Can Vyvanse (lisdexamfetamine), Contrave (bupropion and naltrexone), and Wegovy (semaglutide) be co‑administered?

Can Vyvanse, Contrave, and Wegovy Be Taken Together?

Yes, these three medications can be co-administered with careful monitoring, though no formal studies have evaluated this specific triple combination. The primary concerns are cardiovascular effects (blood pressure and heart rate elevation) and seizure risk from the bupropion component in Contrave, but there are no absolute pharmacokinetic contraindications to using them together. 1

Key Safety Considerations Before Co-Administration

Cardiovascular Monitoring Requirements

• Blood pressure and heart rate must be monitored at baseline and periodically during treatment, especially in the first 12 weeks, as both Vyvanse (lisdexamfetamine, a stimulant) and Contrave (naltrexone/bupropion) can independently elevate these parameters. 1, 2
• Uncontrolled hypertension is an absolute contraindication to both Vyvanse and Contrave, so blood pressure must be controlled before initiating this combination. 1
• Weekly to biweekly blood pressure checks are recommended during titration and the first 8 weeks of combined therapy. 2

Seizure Risk Assessment

• Bupropion (in Contrave) lowers the seizure threshold, with a risk of approximately 0.1% (1 in 1,000) at standard doses of 300 mg/day. 1, 3
• Absolute contraindications for Contrave include: history of seizure disorders, eating disorders (bulimia/anorexia nervosa), abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs, brain tumors, stroke, or head trauma. 1, 3
• The maximum daily dose of bupropion in Contrave is 360 mg (four tablets of 90 mg each), and this limit must not be exceeded when combined with other medications. 1, 2

Opioid Medication Exclusion

• Patients taking any chronic opioid therapy cannot use Contrave because naltrexone is an opioid antagonist that will precipitate severe withdrawal. 1, 2
• Contrave must be discontinued before any procedures requiring opioid analgesia (e.g., colonoscopy with fentanyl). 2

Dosing and Titration Protocol

Contrave Titration Schedule

• Week 1: 1 tablet (8 mg naltrexone/90 mg bupropion) once daily in the morning 1, 2
• Week 2: 1 tablet twice daily 1, 2
• Week 3: 2 tablets in the morning, 1 tablet in the afternoon 1, 2
• Week 4 and beyond: 2 tablets twice daily (maintenance dose) 1, 2
• The second dose should not be taken late in the day to minimize insomnia risk, particularly when combined with Vyvanse. 3, 2

Wegovy (Semaglutide) Dosing

• Wegovy is initiated at 0.25 mg subcutaneously once weekly, with gradual escalation every 4 weeks (0.5 mg, 1.0 mg, 1.7 mg) to the maintenance dose of 2.4 mg weekly. 1
• Gastrointestinal side effects (nausea, constipation) are common and may be exacerbated when combined with Contrave, which also causes nausea. 1

Vyvanse Dosing Considerations

• Standard dosing for ADHD ranges from 30-70 mg once daily in the morning. (General medical knowledge)
• When combined with Contrave, the sympathomimetic effects are additive, requiring closer cardiovascular monitoring. 1

Efficacy Assessment Timeline

• At 12 weeks on the maintenance dose of Contrave, assess whether the patient has lost at least 5% of baseline body weight; if not, discontinue Contrave as they are likely a poor responder. 1, 2
• Wegovy typically demonstrates weight loss of 15-20% over 68 weeks, with most weight loss occurring in the first 6 months. 1
• The combination may provide additive weight loss benefits, though no studies have evaluated this specific triple combination. 4, 5, 6

Neuropsychiatric Monitoring

• All three medications require monitoring for mood changes, anxiety, depression, and suicidal ideation, particularly in patients younger than 24 years. 1, 2
• Bupropion carries a black box warning for increased risk of suicidal thoughts in young adults, especially in the first 1-2 months of treatment. 1, 3
• Studies show no significant difference in depression rates between naltrexone-bupropion and placebo (0.1%-1.3% vs 0.2%-1.6%), but vigilance is required when combining with stimulants. 2

Dose Adjustments for Special Populations

Renal Impairment

• For moderate to severe renal impairment (GFR <90 mL/min), reduce the total daily dose of Contrave by half (1 tablet twice daily instead of 2 tablets twice daily). 1, 3, 2
• Avoid Contrave in end-stage renal disease. 3, 2

Hepatic Impairment

• For moderate to severe hepatic impairment, do not exceed 1 tablet of Contrave daily (total 8 mg naltrexone/90 mg bupropion). 1, 3, 2

Common Pitfalls to Avoid

• Do not combine Contrave with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation, as this can cause hypertensive crisis. 1, 3
• Do not exceed the maximum dose of 360 mg bupropion daily (contained in 4 tablets of Contrave) to maintain seizure risk at 0.1%. 1, 3, 2
• Do not skip cardiovascular monitoring during the first 12 weeks, as this is when blood pressure elevations are most likely to occur. 1, 2
• Do not use this combination in patients with eating disorders (bulimia or anorexia nervosa), as bupropion significantly increases seizure risk in this population. 1, 3

Cardiovascular Safety Evidence

• A systematic literature review of 70 studies (including 7 studies of naltrexone/bupropion) found no increased risk of major adverse cardiovascular events (MACE) with Contrave compared to placebo or active comparators, with differences in MACE proportions not exceeding 2.5%. 4
• However, modest but statistically significant increases in systolic and diastolic blood pressure have been observed with naltrexone-bupropion, necessitating regular monitoring. 2, 4

Clinical Advantages of This Combination

• Contrave may be particularly beneficial for patients with food cravings and addictive eating behaviors, as the naltrexone component blocks opioid-mediated reward pathways. 1, 7, 8
• Wegovy provides the most robust weight loss (15-20% at 72 weeks) and has cardiovascular benefits independent of weight loss. 1
• Vyvanse addresses ADHD symptoms that may contribute to impulsive eating and poor dietary adherence. (General medical knowledge)
• The combination addresses obesity through complementary mechanisms: appetite suppression (Wegovy), reward pathway modulation (Contrave), and improved executive function/impulse control (Vyvanse). 1, 7