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Vol. 26  ·  Naltrexone  ·  July 2026
NALTREXONE
Confirming adherence to an opioid antagonist for OUD and alcohol use disorder

Naltrexone is a specific opioid antagonist used to treat opioid and alcohol use disorder; it blocks opioid receptors and, in alcohol use disorder, reduces craving by blunting reinforcement. It is given orally (ReVia, Depade) or as a monthly IM depot (Vivitrol). Monitoring by LC-MS/MS confirms adherence, measuring naltrexone and its major metabolite 6-beta-naltrexol.1

Why This Matters Now

Unlike agonist therapies, naltrexone provides no reinforcing effect, so adherence is a common challenge, especially with daily oral dosing; the monthly depot (Vivitrol) was developed partly to address this. Confirming naltrexone presence documents adherence between visits.2

⚠ A naltrexone-negative result in a patient prescribed oral naltrexone suggests non-adherence; with the monthly depot, timing relative to the injection matters for interpretation.
Clinical Presentation
CLINICAL EFFECTS
Blocks opioid effects (analgesia, euphoria)
Reduces alcohol craving
Can precipitate withdrawal if opioids present
Hepatotoxicity at high doses (monitor LFTs)
Injection-site reactions (depot)
KEY CAUTIONS
Requires opioid abstinence before starting (7 to 10 days)
Precipitated withdrawal if opioids present
Reduced opioid tolerance raises overdose risk if use resumes
Opioid analgesia is blocked; plan non-opioid pain control
Not an agonist; no misuse potential
Important: Because naltrexone lowers opioid tolerance, a return to prior opioid doses after stopping it carries a high overdose risk. Naltrexone must not be started until the patient is opioid-free (typically 7 to 10 days) to avoid precipitated withdrawal.
UDT Considerations

Naltrexone is an antagonist and does not appear on opioid panels; a dedicated LC-MS/MS test measures naltrexone and 6-beta-naltrexol, with detection above a 10 ng/mL cutoff.3 A positive confirms recent adherence; with the monthly depot, interpret against the injection date, since urinary detection of oral dosing is only 1 to 2 days.

Clinical Guidance
  • Order naltrexone-specific LC-MS/MS to document adherence; it is not on opioid panels.1
  • Confirm opioid abstinence before initiation to avoid precipitated withdrawal.2
  • Counsel on overdose risk from reduced tolerance if opioid use resumes after stopping.
  • Interpret depot (Vivitrol) results against the injection timing, not just the short urinary window.
  • Plan non-opioid analgesia; naltrexone blocks opioid pain relief.
Point-of-Care Testing Availability
Available strips
Naltrexone is an antagonist and is not detected on opioid panels.
Clinical use
Monitoring confirms adherence, not opioid use.
Limitations
LC-MS/MS measures naltrexone and 6-beta-naltrexol (cutoff ~10 ng/mL).
NALTREXONE  |  Clinical & Program Guidance
Tox In Focus Vol. 26  ·  July 2026  ·  Page 2 of 2
Interpreting the Test Result
▲  If Testing Is Positive

Confirms adherence. Naltrexone and/or 6-beta-naltrexol above cutoff indicates recent use.

Depot timing matters. With Vivitrol, interpret against the injection date, not only the short oral window.

Not an opioid result. A naltrexone positive reflects the antagonist, not opioid use.

Metabolism & Urinary Markers

Naltrexone analytes measured on definitive testing.

MetaboliteClinical Significance
Naltrexone (parent)Opioid antagonist; oral half-life ~8 to 10 h.
6-beta-naltrexolMajor urinary metabolite; the main glucuronide-conjugated marker.
Key References
  1. Volpicelli JR, et al. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry. 1992;49(11):876-880.
  2. Substance Abuse and Mental Health Services Administration. Medication-assisted treatment for substance use disorders: naltrexone.
  3. Baselt RC. Disposition of Toxic Drugs and Chemicals in Man. 8th ed. Biomedical Publications; 2008:806-808.
DISCLAIMER: This document is intended for clinical reference and educational purposes only. It does not constitute medical, legal, or professional advice and should not replace independent clinical or programmatic judgment. Content reflects published data available at time of preparation. ToxiPharm LLC makes no warranties regarding completeness or applicability in all settings.  |   © 2026 ToxiPharm LLC  |  toxipharm.org
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