There are two agents that are frequently used in alcohol use disorder. Acamprosate and naltrexone have distinct advantages and disadvantages in the treatment of alcohol use disorder. In this article, we will compare the clinical benefits and risks of acamprosate vs naltrexone.

What do the guidelines say?

Both naltrexone and acamprosate are considered first-line treatments in moderate-to-severe alcohol use disorder per the 2018 APA Practice Guideline For The Pharmacological Treatment Of Patients With Alcohol Use Disorder¹. This is as long as patients “have a goal of reducing alcohol consumption or achieving abstinence, prefer pharmacotherapy or have not responded to nonpharmacological treatments alone, and have no contraindicated to the use of these medications.”¹ This guideline suggests that acamprosate should not be used in those with renal failure as it is contraindicated in those with a CrCl < 30 mL/min. It also recommends against acamprosate in those with mild to moderate renal impairment (a good nugget to remember for board certification exams). This guideline also suggests against using naltrexone in hepatic impairment as well as in those taking opioids as naltrexone is an opioid antagonist³. It is noted, however, that if the patient has concurrent opioid use disorder and alcohol use disorder, naltrexone may be the agent of choice due to its dual role in promoting abstinence from both alcohol and opioids. 

Dosing and Dosage Forms – Acamprosate vs Naltrexone

Acamprosate is only available as a 333 mg delayed-release tablet. The standard dosing is 2 tablets (666 mg) by mouth 3 times daily, dropping to 333 mg by mouth 3 times daily in those with a renal function of 30-50 mL/min². Having to dose the medication this frequently is a potential adherence concern.

Naltrexone, however, is available as both a 50 mg tablet as well as a 380 mg intramuscular injection. The tablet is taken by mouth once daily, and the injection is given in the gluteal muscle every 4 weeks³. Naltrexone may be desirable in patients who struggle with adherence when compared to acamprosate’s 3-time daily dosing. When I think about comparing acamprosate vs naltrexone, the easiest differentiator is renal versus hepatic. Acamprosate should be used cautiously (or avoided) in renal impairment and naltrexone should be used cautiously (or avoided) in hepatic impairment.

Side Effects and Contraindications

Acamprosate has a very short list of contraindications: hypersensitivity and a CrCl < 30 mL/min. Side effects may include diarrhea, anxiety, depression, insomnia, and suicidal ideation². In clinical practice, patients taking acamprosate vs naltrexone will tend to have a significantly higher incidence of diarrhea.

Outside of hypersensitivity, naltrexone’s contraindications include current use of opioids, acute opioid withdrawal, a positive opioid value on a urine screening, opioid dependency that’s being treated by methadone or buprenorphine, and failing a naloxone or naltrexone challenge test. The naloxone/naltrexone challenge test is completed by giving a patient a small amount of naloxone or naltrexone (25 mg). If the patient experiences opioid withdrawal symptoms within 1 hour of administration, the test is considered failed⁴. In areas where buprenorphine is diverted, it may be useful to use naltrexone as naloxone is not effective in “kicking off” buprenorphine⁴. Side effects somewhat differ between the two forms of naltrexone. For the oral tablet, side effects include nausea, headache, and anxiety; for the IM injection, side effects include injection site reaction/pain, diarrhea, vomiting, and increased creatine kinase³. It is worth noting that while the APA guidelines recommend against using naltrexone in those with hepatic insufficiency, there are no dosing changes noted.

This article was written by Brooklyn Mason, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP

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Sources

1. Reus VI, Fochtmann LJ, Bukstein O, Eyler AE, Hilty DM, Horvitz-Lennon M, Mahoney J, Pasic J, Weaver M, Wills CD, McIntyre J, Kidd J, Yager J, Hong S-H. The American Psychiatric Association practice guideline for the pharmacological treatment of patients with alcohol use disorder. American Journal of Psychiatry 2018; 175: 86-90
2. Acamprosate. IBM Micromedex® DrugPoint Summary (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www-micromedexsolutions-com.ezp3.lib.umn.edu/
3. Naltrexone Hydrochloride. IBM Micromedex® DrugPoint Summary (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www-micromedexsolutions-com.ezp3.lib.umn.edu/
4. VIVITROL® (Extended-Release Injectable Naltrexone) Medical Protocol and Procedures. Florida Alcohol & Drug Abuse Association. https://cdn.ymaws.com/www.fadaa.org/resource/resmgr/files/Vivitrol/VivitrolProtocolDRG.pdf Published January 2015.