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Anomalous Observations of Codeine in Patients on Morphine

Urine drug monitoring is used by physicians treating chronic pain patients with opioid therapy. Patients are tested in part to insure that they are not taking other drugs. Therefore, the finding of codeine in a patient who is only prescribed morphine has clinical implications. Morphine preparations are known to have small amounts of codeine as an impurity estimated to be about 0.04%. In a population of 535 pain patients prescribed morphine, Kadian, MS Contin, and/or Avinza, the investigators observed 24 samples that contained codeine >20 ng/mL. Fifteen of the 24 contained codeine >20 and <50 ng/mL. Of the 9 samples that were >50 ng/mL, 7 had high levels of codeine (indicating codeine use), 1 was from a patient who had a prescription for codeine, and 1 was also positive for 6-acetylmorphine, indicating heroin use. A control group of 680 patients taking oxycodone was negative for codeine. The finding of codeine was ascribed to the manufacturing process of the morphine medications. Clinicians and laboratories testing urine for drugs should be aware of this possibility.