What is the recommended dose of intramuscular (IM) naltrexone for opioid or alcohol dependence?

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Recommended Dosage of Intramuscular (IM) Naltrexone for Opioid or Alcohol Dependence

The recommended dose of intramuscular naltrexone is 380 mg administered once every 4 weeks (28 days) for both alcohol and opioid dependence. 1, 2

Dosage Details and Administration

For Injectable Extended-Release Formulation

  • Standard dose: 380 mg IM injection once every 28 days 1, 2
  • Administration site: Gluteal muscle via intramuscular injection 3
  • Preparation: The medication comes as biodegradable polylactide-co-glycolide polymer microspheres containing 34% w/w naltrexone that are reconstituted in an aqueous suspension just prior to administration 2

For Oral Naltrexone (For Comparison)

  • Initial dose: 25 mg for the first 1-3 days to assess tolerability 1
  • Standard maintenance dose: 50 mg once daily 1
  • Alternative dosing schedules: Can be administered daily, twice weekly, or three times weekly based on clinical needs 4

Clinical Efficacy

  • IM naltrexone 380 mg has demonstrated a 25% decrease in heavy drinking days compared to placebo in alcohol-dependent patients 5
  • The extended-release formulation provides continuous naltrexone exposure for 1 month, addressing the poor adherence issues associated with daily oral dosing 3
  • Pharmacokinetic studies show measurable naltrexone plasma concentrations for at least 31 days after a single 380 mg IM injection 3

Patient Selection Considerations

Patients most likely to benefit from naltrexone therapy are:

  • Employed and socially stable individuals 4
  • Those highly motivated to maintain abstinence 4
  • Patients who have been detoxified from opioid dependency for 7 or more days prior to starting treatment 4

Safety Considerations

Contraindications

  • Current use of opioid analgesics
  • Acute opioid withdrawal
  • Failed naloxone challenge test
  • Acute hepatitis or liver failure

Monitoring

  • Liver function tests at baseline and every 3-6 months 1
  • Assessment of treatment response at 12 weeks 1

Common Side Effects

  • Injection site reactions
  • Nausea and vomiting
  • Headache
  • Dizziness
  • Arthralgia 1

Important Clinical Pearls

  1. Naltrexone should always be used as an adjunct to a comprehensive treatment program that includes psychosocial interventions 6

  2. The extended-release formulation avoids first-pass metabolism and changes the exposure ratio of 6β-naltrexol to naltrexone compared with oral administration 3

  3. Treatment discontinuation rates due to adverse events are approximately 14.1% with the 380 mg dose 5

  4. Naltrexone is not a cure for dependency but assists clinicians in addressing medical, psychological, and economic problems associated with substance use disorders 4

  5. For patients with alcohol dependence, those who abstain completely from drinking during the 7 days prior to the first dose may experience greater reductions in drinking days and heavy drinking days 2

References

Guideline

Substance Use Disorder Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Single- and multiple-dose pharmacokinetics of long-acting injectable naltrexone.

Alcoholism, clinical and experimental research, 2006

Research

Naltrexone: its clinical utility.

Advances in alcohol & substance abuse, 1985

Research

Naltrexone in alcohol dependence.

American family physician, 1997

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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