Levorphanol is a synthetic opioid for moderate-to-severe pain with a methadone-like multi-mechanism profile: mu and kappa agonism, NMDA antagonism, and serotonin-norepinephrine reuptake inhibition. Unlike methadone, it is cleared by glucuronidation, so it lacks CYP interactions and QT-prolongation risk.1
The critical interpretive point is cross-reactivity: the test measures racemic d,l-methorphinan and cannot distinguish levorphanol (l-isomer) from dextrorphan (d-isomer), the metabolite of the OTC antitussive dextromethorphan. Use of either drug can produce a positive, so a positive is not specific to levorphanol.2
The levorphanol assay reports racemic d,l-methorphinan and cannot distinguish the levorphanol (l) isomer from the dextrorphan (d) isomer; dextromethorphan use therefore produces a positive result.2 Levorphanol is glucuronidated to an inactive metabolite; a positive confirms exposure to levorphanol or dextromethorphan but not the dose or source.3
Confirms exposure, not the agent. A positive reflects levorphanol or dextromethorphan; the isomers are not separated.2
Check the medication list. OTC cough medicine (DXM) is a common explanation for an unexpected positive.
Long-acting opioid. Levorphanol accumulates; interpret levels with duration in mind.
Timing and cutoff. Absence may reflect timing of last use, dose, or levels below the cutoff.
Short-to-moderate window. Urine detection is estimated at 1 to 3 days.
Not on routine opiate screens. Levorphanol is a synthetic opioid; targeted testing is required.
Levorphanol analytes and the shared-isomer caveat.
| Metabolite | Clinical Significance |
|---|---|
| Levorphanol (l-methorphinan) | The parent opioid; measured as part of racemic d,l-methorphinan. |
| Dextrorphan (d-methorphinan) | DXM metabolite; not separated from levorphanol, so DXM causes a positive. |
| Levorphanol-3-glucuronide | Inactive glucuronide; the main elimination route (no CYP involvement). |