STUDY OBJECTIVE: To evaluate the effects of acetaminophen, naproxen, and acetylsalicylic acid on the pharmacokinetics of the centrally acting analgesic tapentadol in healthy subjects. DESIGN: Two randomized, open-label, crossover, drug-drug interaction studies. SETTING: Clinical research facilities in the United States and Belgium. PARTICIPANTS: Twenty-four healthy adults (2-way crossover study) and 38 healthy adults (3-way crossover study). INTERVENTIONS: In both studies, tapentadol immediate release (IR) 80 mg was administered as a single oral dose alone. In the 2-way crossover study, tapentadol IR was also given with the fifth of seven doses of acetaminophen 1000 mg; in the 3-way crossover study, tapentadol IR was also given with the third of four doses of naproxen 500 mg and the second of two doses of acetylsalicylic acid 325 mg. All treatments were separated by a washout period of 7-14 days. MEASUREMENTS AND MAIN RESULTS: Overall, mean serum concentrations were similar after administration of tapentadol IR alone and after coadministration with acetaminophen or acetylsalicylic acid, and the 90% confidence intervals (CIs) for the ratios of the mean area under the serum concentration-time curve (AUC) from time zero to time of the last measurable concentration (AUC(0-t)) and from time zero extrapolated to infinity (AUC(0-infinity)) and the maximum serum concentration (C(max)) of the combined treatments to those parameters of tapentadol alone were well within 80-125%, representing the accepted range for bioequivalence. Coadministration of naproxen did not significantly alter the C(max) of tapentadol, although a slightly higher serum tapentadol exposure relative to tapentadol alone was observed. Coadministration of naproxen resulted in a mean increase of 17% in AUCs, and the upper limits of the 90% CIs for the ratios of the mean AUC(0-t) and AUC(0-infinity) were slightly outside the upper limit of bioequivalence range of 80-125%(126.47%AUC(0-t) and 126.14%AUC(0-infinity)). CONCLUSION: No clinically relevant changes were noted in the serum concentrations of tapentadol, and accordingly, no dosage adjustments with respect to the investigated pharmacokinetic mechanism of interaction are warranted for the administration of tapentadol given concomitantly with acetaminophen, naproxen, or acetylsalicylic acid.
RCT Entities:
STUDY OBJECTIVE: To evaluate the effects of acetaminophen, naproxen, and acetylsalicylic acid on the pharmacokinetics of the centrally acting analgesic tapentadol in healthy subjects. DESIGN: Two randomized, open-label, crossover, drug-drug interaction studies. SETTING: Clinical research facilities in the United States and Belgium. PARTICIPANTS: Twenty-four healthy adults (2-way crossover study) and 38 healthy adults (3-way crossover study). INTERVENTIONS: In both studies, tapentadol immediate release (IR) 80 mg was administered as a single oral dose alone. In the 2-way crossover study, tapentadol IR was also given with the fifth of seven doses of acetaminophen 1000 mg; in the 3-way crossover study, tapentadol IR was also given with the third of four doses of naproxen 500 mg and the second of two doses of acetylsalicylic acid 325 mg. All treatments were separated by a washout period of 7-14 days. MEASUREMENTS AND MAIN RESULTS: Overall, mean serum concentrations were similar after administration of tapentadol IR alone and after coadministration with acetaminophen or acetylsalicylic acid, and the 90% confidence intervals (CIs) for the ratios of the mean area under the serum concentration-time curve (AUC) from time zero to time of the last measurable concentration (AUC(0-t)) and from time zero extrapolated to infinity (AUC(0-infinity)) and the maximum serum concentration (C(max)) of the combined treatments to those parameters of tapentadol alone were well within 80-125%, representing the accepted range for bioequivalence. Coadministration of naproxen did not significantly alter the C(max) of tapentadol, although a slightly higher serum tapentadol exposure relative to tapentadol alone was observed. Coadministration of naproxen resulted in a mean increase of 17% in AUCs, and the upper limits of the 90% CIs for the ratios of the mean AUC(0-t) and AUC(0-infinity) were slightly outside the upper limit of bioequivalence range of 80-125%(126.47%AUC(0-t) and 126.14%AUC(0-infinity)). CONCLUSION: No clinically relevant changes were noted in the serum concentrations of tapentadol, and accordingly, no dosage adjustments with respect to the investigated pharmacokinetic mechanism of interaction are warranted for the administration of tapentadol given concomitantly with acetaminophen, naproxen, or acetylsalicylic acid.
Authors: Estelle Watson; Akash Khandelwal; Jan Freijer; John van den Anker; Claudia Lefeber; Mariëlle Eerdekens Journal: J Pain Res Date: 2019-10-14 Impact factor: 3.133