Lack of Pharmacokinetic Interaction between Esomeprazole and the Nonsteroidal Anti-Inflammatory Drugs Naproxen and Rofecoxib in Healthy Subjects.

BACKGROUND

We investigated the potential interactions between esomeprazole and a non-selective nonsteroidal anti-inflammatory drug (NSAID; naproxen) or a cyclo-oxygenase (COX)-2-selective NSAID (rofecoxib) in healthy subjects.

METHODS

Two studies of identical randomised, open, three-way crossover design were conducted. Subjects (n = 32 for both studies) were to receive 1 week's treatment with esomeprazole 40mg once daily (studies A and B), naproxen 250mg twice daily (study A), rofecoxib 12.5mg once daily (study B), and esomeprazole in combination with naproxen (study A) or rofecoxib (study B). Study periods were separated by a 2-week washout period.

RESULTS

On day 7 of dosing, the ratios (and 95% CIs) for the area under the plasma concentration-time curve during the dosing interval (AUC(tau)) and observed maximum plasma concentration (C(max)) of esomeprazole and NSAID combination/NSAID alone were 0.98 (0.94, 1.01) and 1.00 (0.97, 1.04), respectively, for study A, and 1.15 (1.06, 1.24) and 1.14 (1.02, 1.28), respectively, for study B. The ratios (and 95% CIs) for AUC(tau) and C(max) of esomeprazole and NSAID combination/esomeprazole alone were 0.96 (0.89, 1.03) and 0.92 (0.85, 1.00), respectively, for study A, and 1.05 (0.96, 1.15) and 1.05 (0.94, 1.18), respectively, for study B. All treatments were well tolerated during the study period.

CONCLUSION

Naproxen and rofecoxib do not interact with esomeprazole, and esomeprazole does not affect the pharmacokinetics of naproxen or rofecoxib. These findings indicate that esomeprazole can be used in combination with NSAIDs without the risk of a pharmacokinetic interaction.