What is the indication for Naltrexone (opioid receptor antagonist)?

Naltrexone Indications

Naltrexone is FDA-approved for two primary indications: treatment of alcohol dependence and blockade of exogenously administered opioids in opioid dependence, and must be used as part of a comprehensive addiction management plan. 1

FDA-Approved Indications

Alcohol Dependence

• Naltrexone is indicated for treatment of alcohol dependence, where it functions by blocking opioid receptors and dampening activation of the reward pathway by alcohol, thereby decreasing excessive drinking and increasing abstinence duration. 2, 1
• The medication reduces alcohol craving and consumption in alcohol-dependent patients, with moderate quality evidence supporting its effectiveness in reducing relapse to heavy drinking. 2, 3
• The 380-mg monthly injection (Vivitrol) is FDA-approved and in widespread use for alcohol dependence treatment. 4, 2

Opioid Dependence

• Naltrexone is indicated for blockade of the effects of exogenously administered opioids in the treatment of opioid dependence. 1
• It works as a competitive antagonist at mu opioid receptors, blocking the euphoric effects of opioids and preventing impulsive opioid use, providing time for patients to consider consequences of relapse and seek support. 4, 2
• The extended-release injectable formulation (Vivitrol, 380-mg monthly) was approved by the FDA for treatment of opioid dependence. 4, 2

Mechanism of Action

• Naltrexone is a pure opioid receptor antagonist that competitively binds to mu, kappa, and delta opioid receptors, markedly attenuating or completely blocking the subjective effects of intravenously administered opioids. 1
• When coadministered with morphine on a chronic basis, naltrexone blocks the development of physical dependence to morphine, heroin, and other opioids. 1
• The medication has a plasma half-life of 4 hours, but its active metabolite (6-β-naltrexol) has a 13-hour half-life, with antagonist effects persisting 2-3 days. 5, 1

Available 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. 4, 2
• Clinical studies indicate that 50 mg blocks the pharmacologic effects of 25 mg of intravenously administered heroin for periods as long as 24 hours. 1
• Doubling the dose provides blockade for 48 hours, and tripling the dose provides blockade for about 72 hours. 1

Extended-Release Injectable

• Vivitrol is a 380-mg monthly injection that provides reliable naltrexone release over 1 month at therapeutic levels. 4, 2, 6
• This formulation significantly improves medication compliance compared to daily oral dosing. 6, 7

Patient Selection Criteria

Optimal Candidates for Opioid Dependence

• Naltrexone has been shown to be most helpful in maintaining abstinence from opioids in highly motivated populations, such as healthcare professionals who cannot or do not wish to take continuous opioid agonist therapy. 4, 2
• Criminal justice populations show significant benefit from naltrexone treatment. 2
• However, naltrexone has had limited success in less motivated patient groups. 4

Optimal Candidates for Alcohol Dependence

• Particularly effective in patients who suffer from high craving, as it reduces craving for alcohol. 8
• Family history and allelic variation in the mu opioid receptor gene predict treatment response to naltrexone. 8

Critical Safety Requirements

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. 2, 5
• Naltrexone will precipitate withdrawal symptomatology in subjects physically dependent on opioids. 4, 1

Contraindications

• Naltrexone cannot be used in patients requiring opioids for pain control, as it blocks pain relief from opioid agonists and causes precipitated withdrawal. 4, 2
• Concomitant use with opioid agonists like oxycodone must be avoided, as naltrexone blocks opioid analgesic effects and can precipitate severe opioid withdrawal. 5

Hepatotoxicity Monitoring

• Naltrexone has been associated with hepatic injury at supratherapeutic doses; therefore, liver function tests at baseline and every 3-6 months are recommended. 4, 2
• At the standard 50 mg dose, hepatotoxicity has not emerged as a clinical problem, though at higher doses it is of concern. 9, 3

Critical Clinical Pitfalls

Overdose Risk After Discontinuation

• Patients who discontinue naltrexone treatment are at increased risk of opioid overdose and death resulting from decreased opioid tolerance. 4, 2
• Opioid overdose education and naloxone should be offered to patients discontinuing naltrexone. 2

Perioperative Management

• Oral naltrexone should be held for 2-3 days prior to elective procedures if opioids are expected to be used perioperatively. 2, 5
• Extended-release naltrexone should be held for 24-30 days after the last injection before elective procedures. 2, 5

Treatment Context

• Naltrexone has not been shown to provide any therapeutic benefit except as part of an appropriate plan of management for the addictions. 1
• It should not be used as exclusive treatment but only as an adjunct to a comprehensive program that includes psychosocial treatment approaches such as Alcoholics Anonymous or professional programs. 3
• Behavioral therapies combined with naltrexone compliance have been repeatedly shown to improve outcomes. 6