What are the contraindications for naltrexone (opioid receptor antagonist)?

Contraindications for Naltrexone

Naltrexone is absolutely contraindicated in patients receiving opioid analgesics, those currently dependent on opioids (including patients on methadone or buprenorphine maintenance therapy), patients in acute opioid withdrawal, individuals who have failed the naloxone challenge test, those with positive urine screens for opioids, and anyone with a history of sensitivity to naltrexone or its components. 1

Primary Contraindications

Naltrexone, as an opioid receptor antagonist, has several important contraindications that must be observed to prevent serious adverse outcomes:

• Current opioid use or dependence:

  • Patients actively using opioid medications for pain management
  • Patients maintained on opioid agonists (e.g., methadone)
  • Patients maintained on partial agonists (e.g., buprenorphine)

• Acute opioid withdrawal state:

  • Naltrexone can precipitate severe, potentially life-threatening withdrawal symptoms

• Failed naloxone challenge test:

  • This test is used to verify a patient is opioid-free before starting naltrexone

• Positive urine screen for opioids:

  • Indicates recent opioid use that would contraindicate naltrexone initiation

• Known hypersensitivity:

  • Previous allergic reaction to naltrexone or any component of the formulation

Clinical Implications and Risks

Administering naltrexone to patients with current opioid dependence can precipitate an accelerated and severe withdrawal syndrome characterized by:

• Agitation (96.2% of cases)
• Altered level of consciousness (38.6%)
• Gastrointestinal symptoms: nausea (28%), vomiting (27.3%), abdominal pain (24.2%), diarrhea (16.7%)
• Bone and muscle pain (15.9%)
• Tachycardia (12.9%)
• Pupillary dilation (11.4%) 2

This precipitated withdrawal can be particularly difficult to manage, with agitation being the most prominent and challenging symptom to control. In severe cases, this can be life-threatening and require intensive supportive care 3.

Perioperative Considerations

For patients already on naltrexone therapy who require surgery:

• Oral naltrexone: Should be held for 2-3 days prior to elective surgical procedures if opioids are expected to be used perioperatively 4
• Extended-release naltrexone: Should be held for 24-30 days after the last injection before elective surgical procedures if opioids are expected to be used 4

This timing is critical because the antagonist effects of naltrexone may persist for several days after discontinuation due to its active metabolite, 6-β-naltrexol, which has a half-life of 13 hours and accumulates during long-term therapy 4.

Important Clinical Pitfalls to Avoid

1. False-positive urine drug screens: Naltrexone metabolites (particularly noroxymorphone) can cause false-positive results for oxycodone on urine drug screens. Confirmatory testing should be conducted if unexpected positive results occur 5.

2. Inadequate opioid-free period: Ensure patients have been completely detoxified from opioids (typically 7-10 days for short-acting opioids, longer for methadone) before initiating naltrexone 6.

3. Failure to recognize polysubstance use: Patients with opioid use disorder often have polysubstance use, which can complicate treatment and withdrawal management 7.

4. Inadequate monitoring: Regular liver function testing is recommended at baseline and every 3-6 months during naltrexone therapy 7.

By carefully screening for these contraindications and following appropriate protocols for naltrexone initiation, clinicians can help prevent serious adverse events and improve treatment outcomes for patients with opioid use disorder or alcohol use disorder.