Naltrexone (PO) Administration Guidelines and Side Effects
Oral naltrexone should be held for 2-3 days prior to elective surgical procedures if opioids are expected to be used perioperatively, due to its opioid antagonist properties that can block analgesic effects and potentially precipitate withdrawal. 1
Administration Guidelines
- Naltrexone is a semisynthetic competitive opioid receptor antagonist with a plasma half-life of 4 hours, while its active metabolite (6-β-naltrexol) has a half-life of 13 hours 1
- For alcohol dependence treatment, the standard dosage is 50 mg once daily 2
- Initial dosing may start with 25 mg on the first day, then increase to 50 mg daily to improve tolerability 3
- Patients must be completely opioid-free for 7-10 days before starting naltrexone to avoid precipitating withdrawal symptoms 2, 3
- For patients with moderate to severe hepatic impairment, dose adjustments may be necessary due to increased naltrexone AUC (approximately 5-10 fold in patients with liver cirrhosis) 2
- Renal impairment requires caution as naltrexone and its primary metabolite are excreted primarily in the urine 2
Perioperative Considerations
- Hold oral naltrexone for 2-3 days prior to elective surgical procedures if opioids are expected to be used perioperatively 1
- For extended-release injectable naltrexone, hold for 24-30 days after the last injection before elective surgical procedures 1
- Patients on naltrexone may require higher doses of opioids for effective analgesia in emergency situations, with increased risk of respiratory depression 2
- If naltrexone is used in combination with naloxone, monitor for symptoms of opioid withdrawal 1
Mechanism of Action
- Naltrexone antagonizes mu (highest affinity), kappa, and delta opioid receptors 1
- It prevents patients from experiencing the euphoric effects of narcotics and alcohol 1
- May reset the reward pathway through an opponent process mechanism 1
- When used for obesity treatment in combination with bupropion, naltrexone antagonizes an inhibitory feedback loop that would otherwise limit bupropion's anorectic properties 1
Side Effects
Common Side Effects (>2% incidence):
- Nausea (10%) 2
- Headache (7%) 2
- Dizziness (4%) 2
- Nervousness/anxiety (4%) 2
- Fatigue (4%) 2
- Insomnia (3%) 2
- Vomiting (3%) 2
- Abdominal pain/cramps 2
- Joint and muscle pain 2
Less Common Side Effects (<2% incidence):
- Loss of appetite, diarrhea, constipation 2
- Increased thirst, irritability 2
- Skin rash 2
- Sexual dysfunction (delayed ejaculation, decreased potency) 2
- Respiratory symptoms (nasal congestion, rhinorrhea, sore throat) 2
Serious Adverse Effects:
- Hepatotoxicity at doses higher than the standard 50 mg daily dose 2, 4
- Depression and suicidal ideation have been reported, though causal relationship is not established 2
- False-positive opioid (specifically oxycodone) urine drug screens due to the naltrexone metabolite noroxymorphone 5
Special Precautions
- Patients should carry identification indicating they are taking naltrexone 2
- Naltrexone blocks the effects of opioids, so patients will not experience pain relief from opioid medications 2
- Monitor liver function before and during treatment 3
- Avoid use in pregnant women, breastfeeding women, and patients under 18 years of age 3
- Patients with a history of depression should be monitored closely for mood changes 2
- Naltrexone is most effective when used as part of a comprehensive treatment program that includes counseling and support 2, 4
Clinical Efficacy
- Meta-analyses have shown oral naltrexone is effective in reducing relapse to heavy drinking but less effective in enhancing abstinence 6
- The effect size for alcohol dependence treatment is modest (0.15-0.2 range) 6
- Long-acting injectable naltrexone has shown a 25% decrease in heavy drinking days compared to placebo 7
- Naltrexone is valuable as supplementary therapy for maintaining abstinence in previously opioid-dependent individuals 3