Can hydroxyzine (an antihistamine) cause a false positive result for fentanyl in drug tests?

Hydroxyzine Can Cause False Positive Results for Fentanyl in Drug Tests

Hydroxyzine, an antihistamine, can cause false positive results for fentanyl in immunoassay-based drug tests due to cross-reactivity issues. 1 This is a significant clinical concern that can lead to misinterpretation of drug test results and potentially serious consequences for patients.

Mechanism and Evidence

• Immunoassay-based drug tests, which are commonly used for initial screening, are susceptible to cross-reactions with various medications, including antihistamines like hydroxyzine 1
• These qualitative tests provide positive/negative results but are prone to false positives due to structural similarities between certain medications and the target substances 1
• Similar to hydroxyzine, diphenhydramine (another antihistamine) has been documented to cause false positive results on fentanyl test strips at concentrations at or above 1 mg/mL 2

Other Medications That Can Cause False Positive Fentanyl Results

• Risperidone and its metabolite 9-hydroxyrisperidone have been confirmed to cross-react with fentanyl immunoassays 3
• A study specifically documented false positive fentanyl screening results in patients treated with long-term injectable risperidone (Risperdal Consta) 4
• High concentrations of illicit stimulants such as methamphetamine and MDMA can also cause false positive results on fentanyl test strips 2

Interpreting Fentanyl Test Results

• The positive predictive value of fentanyl immunoassays has been reported as 85.7%, indicating that approximately 14.3% of positive results may be false positives 5, 1
• Confirmatory testing is essential when fentanyl is detected in a patient not known to be using fentanyl, especially if the patient is taking medications known to cause cross-reactivity 1

Recommendations for Clinical Practice

1. Always document any medications the patient is currently taking (including hydroxyzine) to help interpret drug test results 1

2. Consider the limitations of immunoassay screening tests when interpreting positive fentanyl results in patients taking hydroxyzine 1

3. Perform confirmatory testing using more specific methods such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) to verify positive screening results 1, 6

4. Avoid making clinical decisions based solely on immunoassay results, especially when the patient is taking medications known to cause false positives 1

5. Never dismiss patients from care based solely on urine drug test results that may be false positives 1

Important Considerations

• Confirmatory testing is more expensive and takes longer but provides definitive results that can distinguish between true fentanyl use and false positives from medications like hydroxyzine 6
• Mass spectrometry methods have outstanding specificity and sensitivity for fentanyl and its metabolites, making them the gold standard for confirmation 6
• Unexpected positive results should prompt a conversation with the patient rather than immediate punitive action 1

By understanding the potential for hydroxyzine to cause false positive fentanyl test results and following appropriate confirmation protocols, clinicians can avoid misinterpretation of drug test results and ensure appropriate patient care.