Can tapentadol cause a false-positive urine drug screen result for amphetamine?

To the Editor:

Tapentadol (Nucynta^®, Ortho-McNeil-Janssen Pharmaceuticals, Inc. Raritan, NJ.), is a newer, synthetic analgesic approved in the US in 2008 (immediate-release) and 2011 (extended-release) for acute or chronic management of moderate to severe pain. Tapentadol acts as both a mu opioid receptor agonist and norepinephrine reuptake inhibitor.^1,2 Activity at the alpha-2 adrenoreceptor may, directly or indirectly, contribute to its analgesic effect.³ In comparison to oxycodone, tapentadol has similar analgesia with fewer side effects, delayed tolerance, and reduced withdrawal symptoms.^4,5

Tapentadol (Fig. 1) is structurally similar to amphetamine (Fig. 2). Based upon our prior study showing frequent false positive amphetamine screens with other similar drugs such as bupropion,⁶ we sought to determine whether therapeutic use of tapentadol would be associated with false positive immunoassay amphetamine urine drug screens.

Fig. 1. Structure of tapentadol. (Source: http://en.wikipedia.org).

Fig. 2. Generic structure of amphetamine. (Source: http://en.wikipedia.org).

We recruited patients from a pain management clinic and a rheumatology clinic into a prospective, IRB-approved study. We screened computerized clinic records to identify all patients with scheduled appointments in June through August 2011 and with recorded prescriptions for tapentadol. We met eligible patients on their scheduled appointment days and explained the purpose of the study. We excluded patients who were taking prescription amphetamines or bupropion, who admitted illicit amphetamine use, or who had not taken tapentadol within the 3 days before screening. Screened patients were explicitly allowed to opt out without stating a reason. Enrolled patients provided a spontaneously voided urine specimen on the day of their office visit, which we tested using the Siemens Syva EMIT II^™ immunoassay (Siemens Healthcare Diagnostics; Deerfield, IL). All positive immunoassays would then be confirmed by thin-layer chromatography. We recorded each patient's prescribed dose and asked patients to report the number of doses taken on the study day and the two preceding days.

We screened 21 patients taking tapentadol. We excluded 10 patients (3 had not taken the drug recently, 2 had excluding medications, 2 missed their appointments, 2 declined, 1 researcher unavailable). We enrolled 11 patients (8 women, 3 men) with ages ranging from 31 to 86 years (mean 49.5, median 50). Daily dose ranged from 50 mg/day to the maximum labeled dose of 600 mg/day (mean 268 mg/day, median 200 mg/day). All patients were taking the immediate-release formulation only. All urine specimens produced a negative immunoassay result for amphetamine in all 11 patients.

We relied upon patient self-report for the quantity of tapentadol used in the days before study enrollment, and we did not confirm the presence of tapentadol metabolite in the urine. However, all the screened patients were aware of the purpose of the study and received no compensation for their participation, so we believe their self-reported recent doses to be accurate.

Tapentadol shares structural similarities with both amphetamine and methadone. Although we found no amphetamine cross-reaction with the immunoassay, another recent study has demonstrated cross-reactivity with a similar immunoassay for methadone.⁷

We conclude that therapeutic use of tapentadol up to the maximum recommended dose of 600 mg/day does not produce a false positive urine amphetamine screen.

Declaration of interest

Dr. Brasington reports being a member of the speaker’s bureau for Ortho-McNeil-Janssen Pharmaceuticals. All other authors have not conflicts of interest to disclose. We previously disclosed this information when submitting the manuscript.

This work was supported by NIH grants UL1 RR024992 and TL1 RR024995.