What are the uses for Naltrexone?

Naltrexone Uses

Naltrexone is FDA-approved for two primary indications: treatment of alcohol dependence and blockade of exogenously administered opioids in opioid use disorder, and must be used as part of a comprehensive addiction management plan, not as monotherapy. 1

FDA-Approved Indications

Alcohol Dependence

• Naltrexone functions as a competitive opioid receptor antagonist that blocks opioid receptors and dampens activation of the reward pathway by alcohol, thereby decreasing excessive drinking and increasing abstinence duration 2, 3
• Moderate quality evidence supports naltrexone's effectiveness in reducing alcohol consumption and preventing relapse to heavy drinking 2, 3
• Clinical trials demonstrate that naltrexone 50 mg daily combined with psychosocial treatment reduces relapse rates by approximately 50% compared to placebo (31% vs 60% in one study, 21% vs 41% in another) 1
• Naltrexone reduces alcohol craving and the number of drinking days, with abstinence rates of 51% versus 23% for placebo in controlled trials 1

Opioid Use Disorder

• Naltrexone produces complete blockade of the euphoric effects of opioids in both volunteer and addict populations 1
• Naltrexone is most beneficial for highly motivated patients who cannot or do not wish to take continuous opioid agonist therapy (buprenorphine/methadone) 2, 3
• The medication has been shown to be particularly helpful in maintaining abstinence in highly motivated populations such as healthcare professionals 2, 3
• Criminal justice populations show significant benefit from naltrexone treatment 2
• Adolescents with opioid use disorder should be considered for medication-assisted treatment including naltrexone 2

Formulations and Dosing

Oral Naltrexone

• Available as 50-mg tablets taken daily, or alternatively 100 mg on Mondays and Wednesdays, and 150 mg on Fridays 2, 3
• Oral naltrexone has a plasma half-life of 4 hours, with its active metabolite (6-β-naltrexol) having a 13-hour half-life 4
• Antagonist effects persist for 2-3 days after discontinuation 3, 4

Extended-Release Injectable (Vivitrol)

• 380-mg monthly intramuscular injection approved by the FDA for both alcohol and opioid dependence 2
• Provides reliable naltrexone release over 1 month at therapeutic levels 3, 5
• Significantly improves medication compliance compared to daily oral dosing 3, 5

Off-Label Uses

Naltrexone-Bupropion Combination for Obesity

• Naltrexone antagonizes an inhibitory feedback loop that would otherwise limit bupropion's anorectic properties 4
• The combination activates pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus, promoting release of α-melanocyte-stimulating hormone, an anorectic neuropeptide involved in body weight regulation 4
• Patients with alcohol dependence who describe food cravings or addictive eating behaviors are best candidates for this combination 3

Low-Dose Naltrexone (LDN)

• Low-dose naltrexone refers to doses of 1-5 mg daily used off-label for various conditions 2

Critical Safety Considerations and Contraindications

Opioid-Free Period Requirement

• Patients must be completely opioid-free for a minimum of 7-10 days for short-acting opioids before starting naltrexone to avoid precipitating severe, potentially life-threatening withdrawal 3, 1
• Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks 1
• A naloxone challenge test may be helpful, though a few case reports indicate patients may experience precipitated withdrawal despite negative urine toxicology or tolerating naloxone challenge 1

Absolute Contraindications

• Naltrexone cannot be used in patients requiring opioids for pain control, as it blocks pain relief from opioid agonists and causes precipitated withdrawal 3, 4
• Patients with current opioid dependence or recent opioid use should not receive naltrexone 1

Hepatotoxicity Monitoring

• Cases of hepatitis and clinically significant liver dysfunction have been observed with naltrexone exposure 1
• Liver function tests should be performed at baseline and every 3-6 months due to potential hepatotoxicity at supratherapeutic doses 2, 4
• Patients should be warned of the risk of hepatic injury and advised to seek medical attention if they experience symptoms of acute hepatitis 1
• Naltrexone should be discontinued in the event of symptoms and/or signs of acute hepatitis 1

Overdose Risk After Discontinuation

• Patients who discontinue naltrexone treatment have increased risk of opioid overdose and death due to decreased opioid tolerance 2, 3
• Opioid overdose education and naloxone should be offered to patients discontinuing naltrexone 3

Depression and Suicidality

• Depression, suicide, attempted suicide and suicidal ideation have been reported in postmarketing experience with naltrexone 1
• Alcohol- and opioid-dependent patients taking naltrexone should be monitored for the development of depression or suicidal thinking 1
• Families and caregivers should be alerted to monitor patients for emergence of symptoms of depression or suicidality 1

Perioperative Management

Oral Naltrexone

• Oral naltrexone should be held for 2-3 days prior to elective procedures if opioids are expected to be used perioperatively 2, 3, 4

Extended-Release Naltrexone

• Extended-release naltrexone should be held for 24-30 days after the last injection before elective procedures 2, 3, 4

Common Pitfalls to Avoid

• Never initiate naltrexone without confirming adequate opioid-free period, as precipitated withdrawal can be severe and life-threatening 3, 1
• Do not use naltrexone as monotherapy; it must be part of a comprehensive addiction management plan including psychosocial support 1
• Avoid prescribing naltrexone to patients who may require opioid analgesia, as it blocks opioid effects 3, 4
• Do not fail to assess alcohol-dependent patients for underlying opioid dependence before initiating naltrexone, as precipitated withdrawal has occurred when prescribers were unaware of additional opioid use 1
• Remember that naltrexone does not cure dependency and will work well only when combined with appropriate support mechanisms and psychotherapy 6, 7