Use of Contrave, Naltrexone with Bupropion, Bupropion, or Naltrexone and Major Adverse Cardiovascular Events: A Systematic Literature Review

Abstract

Naltrexone/Bupropion extended release (ER; Contrave) is an extended-release, fixed-dose combination medication of naltrexone (8 mg) and bupropion (90 mg) for patients with obesity or overweight with at least one weight-related comorbidity. Obese and overweight patients with or without comorbidities are at increased cardiovascular (CV) risk. Due to the increased CV risk profile in this patient population, this systematic literature review was conducted to assess human studies reporting major adverse CV events (MACE) and other CV events. A priori eligibility criteria included clinical studies (randomized and observational) published from January 1, 2012, to September 30, 2021, with data comparing users of naltrexone/bupropion ER, naltrexone with bupropion, bupropion without naltrexone, or naltrexone without bupropion versus comparator groups (placebo or other treatments), and with sufficient information to determine the frequency of MACE or other CV adverse events by treatment group. Among 2539 English-language articles identified, 70 articles met the eligibility criteria: seven studies of naltrexone/bupropion ER or naltrexone with bupropion, 32 studies of bupropion, and 31 studies of naltrexone. No studies reported an increased risk of MACE among users of naltrexone/bupropion ER, naltrexone with bupropion, or bupropion or naltrexone individually compared with nonusers. One-half of the available studies (n = 35) reported no (zero) CV events and the other half (n = 35) reported that a non-zero frequency of CV events occurred. Four studies reported data on MACE, including three studies of bupropion and one study of naltrexone/bupropion ER. For composite MACE and its components, the difference in proportions between naltrexone/bupropion ER-, bupropion-, or naltrexone-treated patients compared with active comparators or placebo-treated patients did not exceed 2.5%. In conclusion, the available human evidence does not indicate an increased risk of CV events or MACE following use of naltrexone/bupropion ER, naltrexone with bupropion, or the individual components.

A narrative review of approved and emerging anti-obesity medications

“…There is a need to titrate the dose gradually to minimize side effects. The use of this drug is not advised in patients with uncontrolled blood pressure, patients diagnosed with bulimia nervosa, seizures, or alcohol withdrawal ( Dahlberg et al, 2022 ). Those with an obesity-related BMI of 30–45 kg/m2 and with cardiovascular risk factors were followed up for 56 weeks as part of the COR-I research.…”

Association between body mass index and treatment completion in extended-release naltrexone-treated patients with opioid dependence

“…In contrast, the remaining MAT constituent ( 30 ), opioid antagonist naltrexone (NTX), has been associated with diminished sweet taste’s hedonic appeal ( 31 ), along with decrements in food intake, body fat mass ( 32 ) and BWG ( 33 ). Moreover, in combination with bupropion, NTX is commonly prescribed for weight management in individuals who are overweight or obese ( 34 ). Likewise, NTX analog, samidorphan ( 35 ), counteracts BWG arising in the context of antipsychotic therapy ( 36 ).…”