Intramuscular naltrexone

At 380 mg, decreased appetite (13%), dizziness (13%), and injection site pain (12%) also differed significantly from placebo. Nausea was rated as mild or moderate in 95% of cases, usually occurred only after the first injection, and lasted 1 to 2 days on average.

Nine percent of patients taking naltrexone, 190 mg, or placebo also reported injection site pain. Approximately 1% of all patients dropped out because of injection site reactions.

Patients generally adhered to treatment, with 64% receiving 6 injections and 74% receiving at least 4. By comparison, a meta-analysis³ of oral naltrexone clinical trials showed an average 50% retention rate across studies, most of which lasted only 3 months. Study withdrawals because of adverse events were more prevalent among patients receiving IM naltrexone, 380 mg (14.1%), than among the placebo group (6.7%), but the number of serious adverse events differed little.⁷

Liver enzymes (AST and ALT) did not change significantly during the study. Gamma-glutamyltransferase decreased in all patients, consistent with reduced drinking.

Interactions between IM naltrexone and other medications are probably similar to those observed with oral naltrexone.

Contraindications

Although product labeling was not available when this article was written, IM naltrexone, like its oral form, will likely be contraindicated for patients who:

• are taking opioid analgesics
• are in acute opioid withdrawal
• test positive on urine screen for opioids
• have acute hepatitis or liver failure
• are taking maintenance methadone or buprenorphine or are opioid-dependent.

Patients should be opioid-free for 7 to 10 days before starting IM naltrexone to avoid acute withdrawal symptoms.

Before starting IM naltrexone in patients with a history of opioid abuse, give naloxone, 0.8 mg, to test for withdrawal. Do not start naltrexone if the patient shows signs of opioid withdrawal within 20 minutes of receiving naloxone.

Clinical implications

Long-acting IM naltrexone will make it easier to ensure treatment adherence, compared with oral naltrexone. Giving the drug during the office visit will change your practice patterns, but this increase in hands-on care could strengthen the therapeutic alliance. Compared with interpreting patient self-reports, you can also more accurately document adherence to IM naltrexone therapy.

All alcohol-dependence medications work best when combined with psychosocial treatment, and monthly medication visits alone will not provide patients the cognitive and skill-building work they need to recover. Patients early in recovery need to be seen much more often by you and/or another provider of recovery-oriented psychosocial treatment.

Which patients will be more receptive to in-office treatment is unclear. Patients who have relapsed because of nonadherence to oral medications may be more willing to try IM therapy after you explain its benefits. Similarly, IM naltrexone may be more beneficial to patients who:

• cannot adhere to oral medication because of cognitive problems or impulsivity
• face severe consequences—such as legal problems, loss of parental custody, or loss of employment—if treatment fails.

The optimal duration of IM naltrexone therapy is not known, but the injectable has shown efficacy after 6 months⁷ and 1 year.⁸ Some patients have taken it for more than 3 years.⁸ Before stopping IM naltrexone, consider whether the patient:

• has achieved sobriety
• has developed skills and external support to maintain sobriety
• has reduced craving intensity or time spent preoccupied with alcohol
• shows improved global psychosocial function as reflected in improved relationships, work performance, and general health.

Patients with family histories of alcohol dependence and who reduce days of heavy drinking but do not achieve sobriety on IM naltrexone are probably at higher risk of relapse to heavy drinking after stopping the medication.

Related resources

• Injectable naltrexone Web site. https://alkermes2005.ifactory.com/products/naltrexone.html.

Drug brand names

• IM naltrexone • Vivitrol
• Oral naltrexone • Depade
• Naloxone • Narcan

Disclosure

Dr. Rosenthal is a consultant for Forest Laboratories and Alkermes.