What is the cross-reactivity between morphine and oxycodone?

From the Guidelines

Morphine and oxycodone exhibit significant cross-reactivity on immunoassay drug tests, which can lead to false positives, and therefore, confirmatory testing using gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) is recommended for accurate results. This cross-reactivity occurs due to the similar chemical structures of morphine and oxycodone, despite being distinct compounds, with oxycodone being semi-synthetic and morphine being naturally derived from opium. The degree of cross-reactivity varies depending on the specific test being used, with older immunoassay tests showing higher rates of false positives than newer, more specific assays 1.

Key Considerations

• The conversion factors for different opioids, including morphine and oxycodone, are provided in the CDC clinical practice guideline for prescribing opioids for pain, which can help healthcare providers make informed decisions about opioid prescribing and conversion 1.
• The guideline also notes that equianalgesic dose conversions are only estimates and cannot account for individual variability in genetics and pharmacokinetics, highlighting the need for caution when converting between opioids 1.
• The European Society for Medical Oncology (ESMO) clinical practice guidelines for the management of cancer pain also provide information on the comparison of selected opioids for moderate to severe pain, including morphine and oxycodone, and note that switching to another opioid should be done cautiously with a dose reduction of the newly prescribed opioid 1.

Clinical Implications

• Healthcare providers and patients should be aware of the potential cross-reactivity between morphine and oxycodone when interpreting drug test results, especially in clinical, employment, or legal settings where accurate identification of specific substances is important.
• Patients prescribed oxycodone should inform testing facilities about their medication to help prevent misinterpretation of results.
• The use of confirmatory testing methods, such as GC-MS or LC-MS/MS, can help to accurately distinguish between different opioids and prevent false positives.

From the Research

Cross Reactivity of Morphine and Oxycodone

• The cross reactivity of morphine and oxycodone is not directly addressed in the provided studies, but information on their pharmacokinetics and pharmacodynamics can be found 2, 3, 4, 5.
• Morphine and oxycodone are both opioids used for pain management, but they have different pharmacological profiles 2, 5.
• Oxycodone has a higher relative potency than morphine, which increases the risk of over- and underdosing 5.
• The time to onset of analgesia following intravenous or oral administration of oxycodone is shorter than that of morphine, which may lead to a higher risk of addictive behavior 5.
• Drug-drug interactions involving opioids, including morphine and oxycodone, can be problematic due to their narrow therapeutic index and potential for severe toxicity 3, 4.
• The metabolism of morphine and oxycodone differs, with morphine being metabolized by uridine-5'-diphosphoglucuronosyltransferases (UGTs) and oxycodone being metabolized by the cytochrome P450 (CYP450) system 3, 4.

Pharmacokinetic and Pharmacodynamic Considerations

• The pharmacokinetic basis of drug-drug interactions (DDIs) involving opioids is complex and involves various enzyme systems, including CYP450 and UGTs 3, 4.
• Opioids metabolized by the CYP450 system, such as oxycodone, are associated with numerous DDIs that can result in either a reduction in opioid effect or excess opioid effects 4.
• Conversely, opioids that are not metabolized by the CYP450 system, such as morphine, tend to be involved in fewer CYP450-associated pharmacokinetic DDIs 4.
• The pharmacodynamic effects of morphine and oxycodone, including their analgesic efficacy and potential for addictive behavior, must be considered when selecting an opioid for pain management 2, 5.