What is the recommended dose of naltrexone for an adult patient with a history of opioid addiction or alcohol dependence?

Naltrexone Dosing for Opioid and Alcohol Dependence

For alcohol dependence, the standard dose is 50 mg orally once daily, and for opioid dependence, initiate with 25 mg on day one, then 50 mg daily thereafter if no withdrawal occurs. 1

Standard Dosing Regimens

Alcohol Dependence

• The FDA-approved dose is 50 mg once daily for most patients 1
• This dosing regimen was validated in placebo-controlled trials demonstrating efficacy as adjunctive treatment for up to 12 weeks 1
• The American Academy of Family Physicians confirms that oral naltrexone 50 mg tablets can be taken daily, or alternatively 100 mg on Mondays and Wednesdays with 150 mg on Fridays 2
• Injectable naltrexone (Vivitrol) is administered as 380 mg monthly for both alcohol and opioid dependence 2

Opioid Dependence

• Begin with 25 mg on the first day to test for precipitated withdrawal, then advance to 50 mg daily if tolerated 1
• A dose of 50 mg once daily produces adequate clinical blockade of parenterally administered opioids 1
• Alternative supervised dosing schedules include 50 mg every weekday with 100 mg on Saturday, 100 mg every other day, or 150 mg every third day 1
• Higher single doses above 50 mg carry increased risk of hepatocellular injury 1

Critical Pre-Treatment Requirements

Opioid-Free Period

• Patients must be completely opioid-free (including tramadol) for a minimum of 7-10 days before starting naltrexone 1
• This applies to patients previously dependent on short-acting opioids 1
• Patients transitioning from buprenorphine or methadone may be vulnerable to precipitated withdrawal for as long as 2 weeks 1
• The American Academy of Family Physicians emphasizes that naltrexone cannot be used in patients requiring opioids for pain control as it blocks pain relief from opioid agonists 2

Naloxone Challenge Test

• Perform a naloxone challenge if there is any question of occult opioid dependence 1
• Do not perform the challenge in patients showing clinical signs of opioid withdrawal or whose urine contains opioids 1
• Intravenous method: Inject 0.2 mg naloxone, observe 30 seconds; if no withdrawal, inject 0.6 mg and observe 20 additional minutes 1
• Subcutaneous method: Administer 0.8 mg naloxone and observe for 20 minutes 1
• If withdrawal signs appear (nausea, vomiting, sweating, pupillary dilation, muscle aches, anxiety), the test is positive and naltrexone should not be initiated 1
• If positive, repeat the challenge in 24 hours 1

Special Population Dosing

Renal Impairment

• For moderate-to-severe renal impairment, reduce the total daily dose by 50% to 25 mg daily 2
• The American Gastroenterological Association confirms this dose reduction for patients with GFR <90 mL/min 3

Hepatic Impairment

• For moderate-to-severe hepatic impairment, do not exceed 25 mg daily 2
• Liver function tests should be performed at baseline and every 3-6 months due to potential hepatotoxicity at supratherapeutic doses 2
• Naltrexone is contraindicated in patients with decompensated cirrhosis or acute hepatitis 2

Combination Product: Naltrexone-Bupropion (Contrave)

Titration Schedule for Weight Management

• Week 1: 8 mg naltrexone/90 mg bupropion once daily in the morning (1 tablet) 3
• Week 2: 8 mg naltrexone/90 mg bupropion twice daily (1 tablet AM, 1 tablet PM) 3
• Week 3: 16 mg naltrexone/180 mg bupropion in the morning and 8 mg naltrexone/90 mg bupropion in the evening (2 tablets AM, 1 tablet PM) 3
• Week 4 and beyond: 16 mg naltrexone/180 mg bupropion twice daily (2 tablets AM, 2 tablets PM) for a total of 32 mg naltrexone/360 mg bupropion daily 3

Dose Adjustments for Contrave

• Reduce total daily dose by 50% in moderate-to-severe renal impairment 3
• Maximum dose is 8 mg naltrexone/90 mg bupropion once daily (1 tablet) in moderate-to-severe hepatic impairment 3
• Assess efficacy at 12 weeks and discontinue if less than 5% weight loss is achieved 3

Low-Dose Naltrexone (Off-Label)

• Low-dose naltrexone refers to doses of 1-5 mg daily, used off-label for various chronic pain conditions 2
• The FDA recently granted orphan drug designation for low-dose naltrexone for complex regional pain syndrome 4
• This represents approximately 1/10th of the standard daily dosage 4

Monitoring and Safety

Baseline Assessment

• Screen for depression, anxiety, and insomnia before initiating naltrexone, as it may cause or worsen depression 2
• Assess liver function tests at baseline and every 3-6 months 2
• Monitor blood pressure and heart rate periodically, especially in the first 12 weeks when using naltrexone-bupropion combination 3

Critical Safety Warnings

• Patients who discontinue naltrexone have decreased opioid tolerance and increased risk of overdose and death if they return to opioid use 2
• Educate patients about this increased sensitivity to opioids after naltrexone discontinuation 2
• Naltrexone-bupropion combination is absolutely contraindicated with any opioid therapy, including buprenorphine/naloxone (Suboxone), as naltrexone will precipitate severe withdrawal 2

Treatment Duration and Efficacy

• The placebo-controlled trials demonstrating efficacy used naltrexone 50 mg once daily for up to 12 weeks 1
• Many clinicians recommend one year of treatment, though this has not been well studied 5
• Meta-analyses reveal that oral naltrexone is effective in reducing relapse to heavy drinking but less effective in enhancing abstinence, with effect sizes in the 0.15 to 0.2 range 5
• Naltrexone reduces relapse rates by approximately 50% compared to placebo when combined with behavioral treatment 6

Patient Selection

• Naltrexone is most beneficial for highly motivated patients who cannot or do not wish to take continuous opioid agonist therapy (buprenorphine/methadone) 2
• Factors associated with successful outcomes include sustained therapy, participation in multidisciplinary behavioral and psychotherapy programs, and strong family and social support systems 7
• Criminal justice populations show significant benefit from naltrexone treatment 2
• Naltrexone must be combined with comprehensive psychosocial treatment, including counseling, group therapy, and support programs 2

Common Pitfalls

• Do not initiate naltrexone without confirming adequate opioid-free period, as this will precipitate severe withdrawal 1
• Do not use extended dosing intervals (100 mg every other day or 150 mg every third day) without recognizing the higher risk of hepatocellular injury with single doses above 50 mg 1
• Do not prescribe naltrexone-bupropion combination to patients on chronic opioid therapy 2
• Do not fail to educate patients about overdose risk after naltrexone discontinuation 2