From the Guidelines
Prescription morphine can cause a positive drug screen for codeine due to cross-reactivity between the two substances on standard immunoassay drug tests. This occurs because morphine is metabolized in the body and can convert to small amounts of hydromorphone and codeine, as noted in a study on urine drug testing 1. Standard immunoassay drug tests often cannot distinguish between different opioids like morphine, codeine, and hydrocodone due to their similar chemical structures.
According to a study on prevention and control of seasonal influenza with vaccines, although not directly related to the question, it highlights the importance of understanding the limitations of urine drug testing 1. If you are taking prescribed morphine and need to undergo drug testing, it's essential to inform the testing facility or your employer about your legitimate prescription beforehand. Bringing documentation of your prescription to the testing site can help clarify any positive results.
Some key points to consider:
- Standard urine tests for opiates can detect morphine and codeine, but not synthetic opioids such as oxycodone and hydrocodone 1.
- A positive “opiates” immunoassay detects morphine, which might reflect patient use of morphine, codeine, or heroin, but this immunoassay does not detect synthetic opioids 1.
- If a positive result occurs, request confirmation testing such as gas chromatography-mass spectrometry (GC-MS), which can differentiate between specific opioids and verify that the positive result is consistent with your prescribed medication.
This cross-reactivity between morphine and codeine on drug screens is a normal pharmacological phenomenon and doesn't indicate improper medication use when you're taking prescribed morphine. It's crucial to understand the limitations of urine drug testing and to have a plan for responding to unexpected results, as noted in the study on prevention and control of seasonal influenza with vaccines 1.
From the Research
Codeine Positivity in Urine of Patients Prescribed Morphine
- Patients prescribed morphine may test positive for codeine due to the presence of small amounts of codeine as an impurity in morphine preparations, estimated to be about 0.04% 2.
- A study of 535 pain patients prescribed morphine found that 24 samples contained codeine >20 ng/mL, with 15 of these containing codeine >20 and <50 ng/mL, likely due to the manufacturing process of the morphine medications 2.
- Another study found that urine from patients prescribed morphine only was found to contain codeine at <1% of the morphine concentration, a ratio that was also observed in patients who used heroin 3.
Implications for Urine Drug Testing
- The finding of codeine in a patient who is only prescribed morphine has clinical implications, and clinicians and laboratories testing urine for drugs should be aware of this possibility 2.
- Increasing opiate screening and codeine and morphine confirmation cutoff values can lead to a reduction in the confirmed-positive rate for codeine and morphine 4.
- Careful analysis of urine drug testing results, including assessing the ratio of codeine to morphine (C/M), can help providers determine if patients are compliant with their pain management regimens 3.
Detection of Opioids in Urine
- Opiate immunoassays typically are developed to detect morphine and are most sensitive to morphine and codeine, but may have lower sensitivities for other opioids such as hydrocodone and hydromorphone 5.
- A study found that an opiate immunoassay had sufficient sensitivity to detect hydrocodone and hydromorphone in some urine specimens that screened presumptive negative for these opioids at the established threshold 5.
- Measuring free drug only in urine drug testing may lead to false negative results, and detecting glucuronide metabolites can improve the accuracy of opioid detection 6.