Tramadol/Diclofenac Fixed‐Dose Combination for Acute Pain Management: Bioavailability Assessment of a Generic Product

Abstract

The multimodal analgesia strategy for acute pain involves using 2 or more analgesic medications with distinct mechanisms of action. This study assessed the bioavailability and tolerability of 2 tramadol hydrochloride (50 mg)/diclofenac sodium (50 mg) fixed‐dose combination formulations under fed conditions to attend the Brazilian regulatory requirements for generic product registration. An open‐label, randomized, single‐dose, 2‐period, 2‐way crossover trial was conducted, including healthy subjects of both sexes. Subjects received a single dose of either the test or reference formulation of tramadol/diclofenac fixed‐dose combination tablets with a 7‐day washout period. Blood samples were collected up to 36 hours after dosing for tramadol and 12 hours for diclofenac and quantified using a validated liquid chromatography‐tandem mass spectrometry method. Of 56 subjects enrolled, 53 completed the study. The 90% confidence intervals for maximum plasma concentration and area under the concentration‐time curve from time 0 to the last quantifiable concentration were within acceptable bioequivalence limits of 80%‐125%. Considering the results presented in this study, the test formulation is bioequivalent to the reference formulation and could be interchangeable in medical practice.