Switching from Phentermine to Contrave
Discontinue phentermine immediately and start Contrave the next day using the standard dose escalation protocol, beginning with one 8mg/90mg tablet daily in the morning and increasing by one tablet per week until reaching the target dose of two tablets twice daily. 1
Rationale for Direct Switch
There is no pharmacological requirement for a washout period when transitioning from phentermine to Contrave (naltrexone/bupropion). These medications work through different mechanisms—phentermine is an adrenergic agonist while Contrave combines an opioid receptor antagonist with a dopamine/norepinephrine reuptake inhibitor—and do not have overlapping safety concerns that would necessitate a drug-free interval. 1
Contrave Dose Escalation Protocol
Week 1: One tablet (8mg naltrexone/90mg bupropion) in the morning 1
Week 2: One tablet in the morning + one tablet in the evening 1
Week 3: Two tablets in the morning + one tablet in the evening 1
Week 4 onward: Two tablets in the morning + two tablets in the evening (maximum dose: 32mg/360mg daily) 1
This gradual titration minimizes adverse effects, particularly nausea, constipation, headache, and dizziness. 1
Key Monitoring Parameters
Blood pressure and heart rate: Monitor periodically, especially during the first 12 weeks, as Contrave can elevate both parameters 1
Weight loss efficacy: Discontinue Contrave if the patient has not achieved 5% weight loss at 12 weeks, as continued use is unlikely to provide meaningful benefit 1
Contraindications to verify: Ensure the patient does not have uncontrolled hypertension, seizure disorders, current opioid use, or history of eating disorders (bulimia/anorexia), as these are absolute contraindications to Contrave 1
Important Safety Considerations
Seizure risk: Contrave is contraindicated in patients with seizure disorders and should be used with extreme caution in those at increased seizure risk 1
Opioid interactions: Patients must not be taking opioid medications concurrently, as naltrexone will block opioid effects and precipitate withdrawal in opioid-dependent individuals 1
Cardiovascular disease: Unlike phentermine, which is contraindicated in patients with cardiovascular disease, Contrave does not show increased cardiovascular risk. One large trial (n=8,283) demonstrated no differences in all-cause mortality, cardiovascular mortality, or major adverse cardiovascular events compared to placebo after two years. 2, 3
Pregnancy: Contrave is contraindicated in pregnancy; women of reproductive age must use reliable contraception 1
Expected Outcomes
Contrave produces mean weight loss of 4.8-5.0% at 56 weeks compared to placebo, with 36-57% of patients achieving ≥5% total body weight loss. 1 This is comparable to phentermine's efficacy (5.1% at 28 weeks) but allows for long-term use, unlike phentermine which is FDA-approved only for short-term (12 weeks) treatment. 1
Common Pitfall to Avoid
Do not attempt to continue phentermine while initiating Contrave. Although phentermine is sometimes used off-label for longer than 12 weeks 1, combining it with Contrave offers no additional benefit and increases the risk of adverse cardiovascular effects, particularly elevated blood pressure and heart rate. 1