What are the potential side effects of naltrexone (opioid receptor antagonist)?

Potential Side Effects of Naltrexone

Naltrexone can cause various side effects including nausea, constipation, headache, dizziness, insomnia, dry mouth, anxiety, and abdominal pain, with nausea being the most common adverse effect leading to discontinuation. 1

Common Side Effects

• Gastrointestinal effects: Nausea (4.6-9.6%), vomiting (0.7-2%), constipation, abdominal pain/cramps (24.2%), diarrhea (16.7%) 1, 2
• Neurological effects: Headache (7%), dizziness (4%), insomnia (3%), anxiety (2%), somnolence (2%) 1, 3
• Other common effects: Dry mouth, fatigue (4%), irritability, elevated heart rate 1

Serious Side Effects and Safety Concerns

• Hepatocellular injury: Can occur at higher doses (300 mg/day, which is 5x the typical dose); elevated liver enzymes have been reported 3
• Precipitation of opioid withdrawal: Naltrexone can cause severe withdrawal symptoms in patients who are not completely opioid-free, including agitation (96.2%), altered consciousness (38.6%), nausea, vomiting, and abdominal pain 3, 2
• Psychiatric effects: Depression, suicidal ideation, and suicidal attempts have been reported, though causal relationship is not established 3
• Cardiovascular effects: Increased blood pressure, tachycardia (12.9%) 1, 2

Special Considerations

• Contraindications:

  • Patients currently taking opioids or in acute opioid withdrawal 1
  • Patients with acute hepatitis or liver failure 3
  • Pregnant women or those trying to conceive 1

• Drug interactions:

  • Monoamine oxidase inhibitors 1
  • Opioid medications - naltrexone blocks their effects and may precipitate withdrawal 1
  • Should be discontinued before procedures requiring opioid analgesia 1

Low-Dose Naltrexone (LDN) Side Effects

When used at lower doses (2.5-4.5 mg) for conditions like chronic pain, fibromyalgia, or inflammatory conditions:

• Neurological side effects are most common (vivid dreams, drowsiness, dizziness) 4, 5
• Generally well-tolerated with approximately 32% of patients reporting adverse effects 5
• About 27% of patients may discontinue due to side effects 4

Monitoring Recommendations

• Liver function tests: Monitor before starting treatment and periodically thereafter, especially at higher doses 3
• Mental health assessment: Monitor for depression or suicidal ideation, particularly in young adults during the first few months of treatment 1
• Blood pressure and heart rate: Monitor regularly, especially in patients with cardiovascular conditions 1

Dosing Considerations

• For alcohol use disorder: Standard dose is 50 mg daily 6
• For obesity management (as part of naltrexone/bupropion combination): Typically 32 mg naltrexone/360 mg bupropion daily 1
• For chronic pain (off-label): Low doses of 2.5-4.5 mg daily 4, 5, 7

When using naltrexone, it's important to recognize that side effect profiles differ based on the condition being treated and the dosage used, with higher doses generally associated with more adverse effects 3, 4.