ACE-CAA Issue 4 Sample Question

A combined bupropion/naltrexone tablet (Contrave) is approved by the US Food and Drug Administration (FDA) for which of the following indications?

A. Chronic weight management  ✔

B. Irritable bowel syndrome X

C. Pruritus X

Read the discussion below.

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Discussion

Naltrexone is a competitive opioid antagonist that has been approved as an oral medication for the treatment of alcohol use disorder and opioid use disorder. More recently, a once-monthly intramuscular formulation was developed for improved patient adherence. Naltrexone has also been used off label to treat a variety of conditions, including pruritus and compulsive disorders. There has been increasing interest in the use of lower-dose naltrexone for a variety of conditions (eg, irritable bowel syndrome). In 2014, the US Food and Drug Administration approved a combined bupropion/naltrexone tablet (Contrave) for chronic weight management. Each tablet contains 90 mg of bupropion and 8 mg of naltrexone with a recommended titration to 4 tablets per day, for a daily dose of 32 mg of naltrexone.

Because it is a competitive opioid antagonist, naltrexone may present challenges for perioperative pain control with opioids. An ideal discontinuation time to allow for full opioid agonism has not been established. In chronic dosing, naltrexone appears to have a mean elimination half-life of approximately 10 hours, but its active metabolite, 6β naltrexol, has a longer half-life. Further, studies have shown that the half-life for µ-receptor blockade with chronic naltrexone therapy may be as long as 100 hours.

It has been suggested that oral naltrexone be discontinued approximately 2 to 3 days prior to anticipated use of full opioid agonists. Management of patients who have been receiving intramuscular naltrexone is much more complicated and may require a delay of up to 4 weeks after the last injection prior to the administration of full opioid agonists. Discontinuation of naltrexone should be done in close coordination with the prescribing physician. Bupropion discontinuation syndrome is possible.

Close monitoring may be required postoperatively, as attenuation and enhancement of the response to opioids have both been observed in the setting of chronic naltrexone therapy, increasing the risk of potential adverse effects.

REFERENCES

1. Contrave—a combination of bupropion and naltrexone for weight loss. Med Lett Drugs Ther. 2014;56(1455):112-114.
2. Gropper MA, Cohen NH, Eriksson LI, Fleisher LA, Leslie K, Wiener-Kronish JP, eds. Miller’s Anesthesia. 9th ed. Elsevier; 2020:733.
3. Harrison TK, Kornfeld H, Aggarwal AK, Lembke A. Perioperative considerations for the patient with opioid use disorder on buprenorphine, methadone, or naltrexone maintenance therapy. Anesthesiol Clin. 2018;36(3):345-359. doi:10.1016/j.anclin.2018.04.002
4. Sudakin D. Naltrexone: not just for opioids anymore. J Med Toxicol. 2016;12(1):71-75. doi:10.1007/s13181-015-0512-x

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