Guidelines for Co‑Administration of Vyvanse®, Contrave®, and Wegovy®

Safety Monitoring

Baseline and periodic cardiovascular monitoring (blood pressure and heart rate) during the first 12 weeks is required because both Vyvanse® and Contrave® can raise these parameters. 2
Uncontrolled hypertension is an absolute contraindication to initiating Vyvanse® or Contrave®; blood pressure must be controlled beforehand. 2
Weekly to biweekly blood pressure checks are advised during titration and the initial 8 weeks of combined therapy. 4
Bupropion in Contrave® lowers the seizure threshold, with an estimated seizure risk of ~0.1 % (1 in 1,000) at the standard 300 mg/day dose. 2
Absolute contraindications for Contrave® include a history of seizure disorders, eating disorders (bulimia or anorexia nervosa), abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs, brain tumors, stroke, or head trauma. 2
Patients on chronic opioid therapy must not use Contrave® because naltrexone precipitates opioid withdrawal. 2
Contrave® should be stopped before any procedure requiring opioid analgesia (e.g., colonoscopy with fentanyl). 4
When Vyvanse® is combined with Contrave®, additive sympathomimetic effects necessitate closer cardiovascular surveillance. 2

Week 1: 1 tablet (8 mg naltrexone / 90 mg bupropion) once daily in the morning.
Week 2: 1 tablet twice daily.
Week 3: 2 tablets in the morning, 1 tablet in the afternoon.
Week 4 and beyond: 2 tablets twice daily (maintenance dose).
These titration steps are based on the recommended schedule in obesity guidelines.* 5
The total daily bupropion dose must not exceed 360 mg (four tablets); exceeding this increases seizure risk above 0.1 %. 5

Initiate at 0.25 mg subcutaneously once weekly, then increase every 4 weeks to 0.5 mg, 1.0 mg, and 1.7 mg, reaching the maintenance dose of 2.4 mg weekly. 7
Gastro‑intestinal adverse effects (nausea, constipation) are common and may be intensified when combined with Contrave®, which also causes nausea. 2

Standard adult ADHD dosing ranges from 30 mg to 70 mg taken once daily in the morning. 6

At 12 weeks on the maintenance dose of Contrave®, assess whether the patient has achieved ≥5 % loss of baseline body weight; failure to do so suggests poor response and warrants discontinuation. 1
Wegovy® typically produces 15–20 % body‑weight reduction over 68 weeks, with the majority of loss occurring within the first 6 months. 7

All three agents require monitoring for mood changes, anxiety, depression, and suicidal ideation, especially in patients younger than 24 years. 2
Bupropion carries a black‑box warning for increased risk of suicidal thoughts in young adults, particularly during the first 1–2 months of therapy. 2

Moderate to severe renal impairment (eGFR < 90 mL/min) – halve the total daily Contrave® dose (e.g., 1 tablet twice daily). 5
End‑stage renal disease – avoid Contrave® altogether. 6
Moderate to severe hepatic impairment – limit Contrave® to ≤1 tablet daily (8 mg naltrexone / 90 mg bupropion). 5

Do not combine Contrave® with monoamine‑oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation, due to risk of hypertensive crisis. 2
Do not exceed the maximum bupropion dose of 360 mg/day (four Contrave® tablets) to keep seizure risk at ~0.1 %. 5
Do not omit cardiovascular monitoring during the first 12 weeks, as this period carries the highest risk for blood‑pressure elevations. 2
Avoid this combination in patients with eating disorders (bulimia or anorexia nervosa) because bupropion markedly raises seizure risk in this group. 2

Contrave® may be especially useful for patients with strong food cravings or addictive‑eating behaviors, as naltrexone blocks opioid‑mediated reward pathways. 2
Wegovy® provides the most robust weight‑loss effect (15–20 % at ~72 weeks) and confers cardiovascular benefits independent of weight loss. 7
Vyvanse® improves ADHD symptoms that can contribute to impulsive eating and poor dietary adherence. 3
Together, the three agents target obesity through complementary mechanisms: appetite suppression (Wegovy®), reward‑pathway modulation (Contrave®), and enhanced executive function/impulse control (Vyvanse®). 2