Medications Causing False Positives for Fentanyl, Amphetamines, and Methamphetamine
Direct Answer
Risperidone (including long-acting injectable Risperdal Consta) and ziprasidone cause false-positive fentanyl results, while pseudoephedrine, bupropion, trazodone (via its metabolite m-CPP), and metoprolol cause false-positive amphetamine/methamphetamine results on immunoassay screening tests. 1, 2, 3, 4, 5, 6
False Positives for Fentanyl
Antipsychotic Medications
- Risperidone (particularly long-acting injectable formulations like Risperdal Consta) causes false-positive fentanyl results on rapid commercial screening kits and immunoassay tests. 1
- Ziprasidone has been documented to cause false-positive fentanyl results on urine drug screens, likely due to structural similarities with risperidone. 2
High Concentrations of Stimulants (Testing Context)
- Methamphetamine and MDMA at concentrations ≥1 mg/mL can cause false-positive fentanyl results on fentanyl test strips, though this is primarily relevant for street drug checking rather than clinical urine testing. 7
False Positives for Amphetamines and Methamphetamine
Over-the-Counter Medications
- Pseudoephedrine (found in cold medications) is the most commonly cited cause of false-positive amphetamine screening results. 3, 4, 8
- Dextromethorphan (cough suppressant) can cause false-positive results. 3, 4
Prescription Medications
- Bupropion causes false-positive amphetamine results on standard immunoassay drug tests. 4
- Trazodone causes false-positive amphetamine results through its metabolite meta-chlorophenylpiperazine (m-CPP), which shows strong cross-reactivity with amphetamine immunoassays (correlation r=0.990). 5, 9
- Metoprolol (beta-blocker) causes false-positive results for both amphetamines (at 200 μg/mL) and MDMA (at 150 μg/mL), with its metabolites also contributing to cross-reactivity. 6
Additional Considerations
- Diphenhydramine at high concentrations (≥1 mg/mL) can cause false-positive amphetamine results, though this is more relevant in street drug testing contexts. 7
Critical Clinical Actions When Encountering Positive Results
Immediate Steps
- Obtain complete medication history including all prescription medications, over-the-counter drugs, and supplements before interpreting any positive drug test. 3, 8
- Request confirmatory testing using gas chromatography-mass spectrometry (GC-MS) before making any consequential clinical decisions, as this method can definitively distinguish true positives from medication-related false positives. 3, 8
Understanding Test Limitations
- Standard immunoassay screening tests are designed as presumptive tests only and have known limitations in specificity due to cross-reactivity with structurally similar compounds. 3, 8, 5
- Preliminary screening tests yield more false-positive results compared to confirmatory tests and should never be considered definitive. 3, 4
- Common enzyme-linked immunoassays do not consistently detect all opioids (including fentanyl in some panels) or distinguish between prescribed medications and illicit substances. 3
Common Pitfalls to Avoid
Testing Timing
- Test patients immediately upon admission before administering any medications that could cause positive results (e.g., pain medications during labor and delivery can cause false positives). 3
Interpretation Errors
- Never dismiss patients or make punitive decisions based solely on a single immunoassay result without confirmatory testing. 8
- False-positive results have lower positive predictive value when clinical findings do not suggest drug use. 8
- Many healthcare providers have inadequate training in interpreting urine drug tests, and incorrect interpretation can have severe consequences including loss of child custody or legal implications. 8
Laboratory Communication
- Discuss unexpected positive results with laboratory personnel or toxicologists before making clinical decisions. 8
- Understand your specific laboratory's testing panel components and limitations, as panels vary by institution based on local drug usage profiles. 3, 4
Additional Context on Specific Substances
Poppy Seeds
- Poppy seed ingestion causes false-positive results for morphine and codeine on both screening and confirmatory tests (GC-MS). 3, 4
Fluoroquinolone Antibiotics
- Fluoroquinolone antibiotics can cross-react with opiate immunoassay screens (not amphetamine or fentanyl screens). 8