What are the implications of a urine drug screen positive for Levorphanol at a marked elevation?

From the Guidelines

A urine drug screen positive for Levorphanol at a marked elevation indicates potential misuse or overdose, and clinicians should promptly evaluate the patient's risk factors for opioid-related harms and consider a broad differential diagnosis before taking action 1.

Key Considerations

• Levorphanol is a mu-, delta-, and kappa-opioid receptor agonist with a shorter half-life and more predictable metabolism compared to methadone 1.
• Urine drug testing is imperfect and can be falsely positive due to cross-reactivity with other agents, and gas chromatography/mass spectroscopy is used for confirmatory testing 1.
• Clinicians should review the patient's history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or dangerous combinations that put him or her at high risk for overdose 1.
• Risk factors for opioid-related harms, such as history of overdose, history of substance use disorder, higher opioid dosages (≥50 MME/d), or concurrent benzodiazepine use, should be evaluated and strategies to mitigate risk should be incorporated into the management plan 1.

Clinical Implications

• Unexpected UDT results and concerning behaviors should not be used to discharge patients from the practice, but rather to reevaluate the current treatment strategy and consider alternative clinical services, such as substance use treatment 1.
• Naloxone should be considered for patients at increased risk of overdose, including those with a history of overdose, substance use disorder, or higher opioid dosages 1.
• Levorphanol may offer benefits for certain populations, such as the elderly, with lessened prescribing complexities and adverse effects compared to methadone 1.

From the FDA Drug Label

Concentration–Adverse Reaction Relationships There is a relationship between increasing levorphanol plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression Very high plasma concentrations of levorphanol can be reached in patients on chronic therapy due to the long half-life of the drug One study in 11 patients using the drug for control of cancer pain reported plasma concentrations from 5 to 10 ng/mL after a single 2 mg dose and up to 50 to 100 ng/mL after repeated oral doses of 20 to 50 mg/day.

The implications of a urine drug screen positive for Levorphanol at a marked elevation are:

• Increased risk of adverse reactions: such as nausea, vomiting, CNS effects, and respiratory depression due to high plasma concentrations of levorphanol.
• Potential for toxicity: very high plasma concentrations of levorphanol can be reached in patients on chronic therapy, which may lead to serious adverse effects.
• Need for dose adjustment: the dose of levorphanol may need to be adjusted to avoid excessive sedation due to drug accumulation, especially when converting a patient from another opioid to levorphanol 2.
• Monitoring for adverse effects: patients with high plasma concentrations of levorphanol should be closely monitored for signs of adverse effects, such as respiratory depression, and treated promptly if they occur 2.

From the Research

Implications of a Urine Drug Screen Positive for Levorphanol

• A marked elevation in levorphanol levels in a urine drug screen may indicate ingestion of levorphanol, but it can be challenging to distinguish between levorphanol and dextromethorphan ingestion based on urine biomarkers alone 3.
• The presence of dextromethorphan or 3-methoxymorphinan in the urine sample can help differentiate between levorphanol and dextromethorphan ingestion, but an enantiomeric analysis may be necessary to confirm the results 3.
• Clinicians should consider the parameters of their laboratory's testing method when interpreting levorphanol drug test results, as the potential exists for patients prescribed levorphanol to ingest dextromethorphan and appear compliant with levorphanol therapy 3.
• Urine drug testing can be used to monitor adherence to medication regimens, including levorphanol, and to identify patterns of drug use 4.
• The interpretation of urine drug test results should be done with caution, considering pharmacological properties and the presence or absence of the parent drug and its metabolites 4, 5, 6, 7.
• False-positive and false-negative results can occur with urine drug testing, and clinicians should be aware of the limitations and potential pitfalls of these tests 5, 7.
• Urine samples can be adulterated with other substances to mask positive results on urine drug testing, and clinicians should be familiar with these substances and their effects on urine drug testing 7.