What is the recommended dosing for Contrave (naltrexone-bupropion)?

From the Guidelines

Contrave should be started at a low dose and gradually increased to minimize side effects, with a typical dosing schedule of one tablet (8 mg naltrexone/90 mg bupropion) taken once daily in the morning for the first week, increasing to two tablets taken twice daily (morning and evening) by week four, for a total daily dose of 32 mg naltrexone/360 mg bupropion 1. The recommended dosing begins with one tablet taken once daily in the morning for the first week. In week two, this increases to one tablet in the morning and one in the evening. Week three advances to two tablets in the morning and one in the evening. By week four, the target maintenance dose is reached with two tablets taken twice daily (morning and evening), for a total daily dose of 32 mg naltrexone/360 mg bupropion. Contrave should be taken with food and swallowed whole, not crushed or chewed. If significant side effects occur, dose escalation may be delayed. The medication should be evaluated after 12 weeks; if less than 5% weight loss has occurred, discontinuation should be considered as further benefits are unlikely. Common side effects include nausea, constipation, headache, and insomnia, as reported in studies such as 1 and 1. This gradual titration schedule helps the body adjust to the medication while minimizing adverse effects, as both active ingredients can cause significant side effects when started at full doses. It is essential to consider the potential safety concerns and contraindications, such as uncontrolled hypertension, seizure disorders, and chronic opioid therapy, as outlined in 1 and 1. The most recent and highest quality study, 1, provides guidance on the use of Contrave for obesity management, emphasizing the importance of careful patient selection and monitoring. Overall, the evidence supports the use of Contrave as a safe and effective treatment for obesity, with a recommended dosing schedule and careful consideration of potential side effects and contraindications 1.

From the Research

Contrave Dosing

• The recommended dosing for Contrave, a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release, is not explicitly stated in the provided studies, but the studies mention the use of sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets 2.
• The studies also mention a 3-week dose escalation period 2.
• The efficacy and safety of Contrave were assessed in four randomized, double-blind, placebo-controlled, 56-week Phase III clinical trials in 4536 adult subjects, with an average weight loss from baseline across the four studies of approximately 11-22 lbs (5-9 kg) 3.

Efficacy of Contrave

• The combination of naltrexone and bupropion was shown to be effective in achieving weight loss, with a placebo-subtracted mean weight loss of 4.7% (range 3.2-5.2%) after 1 year 4.
• The proportion of patients achieving ≥5% weight loss with naltrexone/bupropion ranged from 26 to 33% (p < 0.001 vs. placebo in each trial) 4.
• Contrave was also associated with significant improvements in cardiometabolic markers, including waist circumference, serum triglycerides, and insulin resistance 3, 5.

Safety of Contrave

• Common side effects associated with Contrave include nausea, constipation, vomiting, dizziness, and dry mouth 2, 4, 5.
• Serious adverse effects, which were very rare, included suicidal thoughts and seizures 5.
• The cardiovascular safety of Contrave remains uncertain and will require evaluation in a new adequately powered outcome trial 6.