What is the typical dosing regimen for naltrexone (opioid receptor antagonist)?

Naltrexone Dosing

Standard Dosing for Opioid Dependence

For opioid dependence treatment, initiate naltrexone at 25 mg on day one, then advance to 50 mg once daily if no withdrawal signs occur. 1

• The 50 mg daily dose provides adequate clinical blockade of parenterally administered opioids 1
• Patients must be completely detoxified from opioids before starting naltrexone, with a recommended opioid-free period of 7-10 days 1, 2
• The drug-free state should be verified through urine screening or naloxone challenge testing before initiating therapy 1, 2

Naloxone Challenge Test Protocol

Before starting naltrexone, perform a naloxone challenge test to confirm adequate opioid clearance 1:

Intravenous route:

• Inject 0.2 mg naloxone IV and observe for 30 seconds for withdrawal signs 1
• If no withdrawal occurs, inject 0.6 mg naloxone and observe for 20 additional minutes 1

Subcutaneous route:

• Administer 0.8 mg naloxone subcutaneously and observe for 20 minutes 1

• If withdrawal signs appear (nausea, vomiting, sweating, pupillary dilation, anxiety, muscle aches), the test is positive—do not initiate naltrexone and repeat the challenge in 24 hours 1

• If the test is negative with no withdrawal signs, naltrexone therapy may be started 1

Alternative Dosing Schedules

For supervised administration programs, flexible dosing regimens are acceptable 1:

• 50 mg every weekday with 100 mg on Saturday 1
• 100 mg every other day 1
• 150 mg every third day 1

Important caveat: Extended dosing intervals may reduce the degree of opioid blockade, and single doses above 50 mg carry higher risk of hepatocellular injury 1

Low-Dose Naltrexone for Chronic Pain

For neuropathic pain conditions, low-dose naltrexone (LDN) should be initiated at 1.5 mg at bedtime, with gradual increases of 1.5 mg every two weeks to a maximum of 4.5 mg at bedtime. 3

• LDN (3-5 mg range) has demonstrated efficacy in fibromyalgia, complex regional pain syndrome, and painful diabetic neuropathy 3
• The mechanism involves antagonism of toll-like receptor 4, reducing pro-inflammatory cytokines and modulating microglial activity 3
• Common side effects include headache, tachycardia, and vivid dreams 3
• This represents approximately 1/10th of the standard daily dosage used for addiction treatment 4

Alcohol Dependence Dosing

For alcohol dependence, the standard dose is 50 mg once daily 1:

• Treatment success requires integration into a comprehensive management plan with compliance-enhancing techniques 1
• Long-acting injectable formulations (380 mg IM every 28 days) are available for patients with adherence difficulties, providing continuous naltrexone exposure for one month 5

Critical Safety Considerations

Contraindications and monitoring requirements:

• Do not administer to patients currently dependent on opioids or in acute opioid withdrawal 1
• Contraindicated in pregnancy, breastfeeding, children under 18 years, and patients with renal failure 2
• Perform liver enzyme testing before and during treatment due to hepatotoxicity risk 1, 2
• Patients must understand that naltrexone blocks opioid effects—attempting to overcome this blockade with large opioid doses can result in fatal overdose 1

Patient Selection and Prognosis

Patients most likely to benefit from naltrexone therapy are those who are 6:

• Employed and married with stable social support 6

• Previously stabilized on low-dose methadone before detoxification 6

• Detoxified from opioids for 7 or more days 6

• Highly motivated for maintenance on a non-opioid agent 6

• Retention rates with naltrexone are higher than traditional drug-free treatment but lower than methadone-supported treatment 2

• Naltrexone does not cure dependency—it assists in managing medical, psychological, and economic problems associated with opioid abuse 6