An integrated safety analysis of combined acetaminophen and ibuprofen (Maxigesic®/ Combogesic®) in adults
Received 9 October 2018
Accepted for publication 2 January 2019
Published 8 February 2019 Volume 2019:12 Pages 621—634
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 3
Editor who approved publication: Dr Michael Ueberall
Phillip Aitken,1 Ioana Stanescu,1 Rebecca Playne,1 Jennifer Zhang,1 Christopher MA Frampton,2 Hartley C Atkinson1
1Drug Development, AFT Pharmaceuticals Ltd, Auckland, New Zealand; 2Department of Medicine, University of Otago, Christchurch, New Zealand
Introduction: Acetaminophen (APAP) and ibuprofen (IBP) are two analgesic compounds with a long history of use. Both are considered safe at recommended over-the-counter daily doses. Chronic use, high doses, or concomitant medication can produce safety risks for both drugs. APAP is associated with increased risk of hepatic injury, while IBP can produce gastric bleeding and thromboembolic events. Using a combination of APAP and IBP provides superior analgesia without transgressing daily dose limits of each individual drug.
Methods: The present study aimed to determine if treatment with a fixed-dose combination (FDC) containing APAP and IBP results in any unexpected adverse events (AEs) and/or changes in the safety profiles of its two ingredients compared to monotherapy. The analysis will examine clinical safety data obtained from either single dose trials, multiple dose trials, a long-term exposure trial, and post-marketing surveillance data of APAP/IBP FDC tablets (Maxigesic®/Combogesic®, AFT Pharmaceuticals Ltd). The largest dataset was obtained by pooling the four randomized-controlled, multiple-dose clinical studies with either APAP 325 mg + IBP 97.5 mg (FDC 325/97.5, three tablets per dose) or APAP 500 mg + IBP 150 mg (FDC 500/150, two tablets per dose). At maximum doses, the two FDCs are bioequivalent, permitting the pooling of data for the analysis of safety.
Results: A safety population of 922 patients who received full doses of either FDC, APAP alone, IBP alone, or placebo was compiled from the four studies. A total of 521 AEs were experienced with the incidence of FDC AEs similar to or below either monotherapy group or placebo. The FDC did not alter the incidence and percentage of the most common AEs, including gastrointestinal events and postoperative bleeding.
Conclusion: Overall, the FDC is well tolerated and has a strong safety profile at single and multiple doses with improved efficacy over monotherapy.
Keywords: paracetamol, nonsteroidal anti-inflammatory drugs, surgical pain, postoperative analgesia, multimodal pain management
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