PMID- 30804681
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231005
IS  - 1178-7090 (Print)
IS  - 1178-7090 (Electronic)
IS  - 1178-7090 (Linking)
VI  - 12
DP  - 2019
TI  - An integrated safety analysis of combined acetaminophen and ibuprofen (Maxigesic 
      ((R)) /Combogesic((R))) in adults.
PG  - 621-634
LID - 10.2147/JPR.S189605 [doi]
AB  - 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((R))/Combogesic((R)), 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.
FAU - Aitken, Phillip
AU  - Aitken P
AD  - Drug Development, AFT Pharmaceuticals Ltd, Auckland, New Zealand, 
      phillip.aitken@aftpharm.com.
FAU - Stanescu, Ioana
AU  - Stanescu I
AD  - Drug Development, AFT Pharmaceuticals Ltd, Auckland, New Zealand, 
      phillip.aitken@aftpharm.com.
FAU - Playne, Rebecca
AU  - Playne R
AD  - Drug Development, AFT Pharmaceuticals Ltd, Auckland, New Zealand, 
      phillip.aitken@aftpharm.com.
FAU - Zhang, Jennifer
AU  - Zhang J
AD  - Drug Development, AFT Pharmaceuticals Ltd, Auckland, New Zealand, 
      phillip.aitken@aftpharm.com.
FAU - Frampton, Christopher M A
AU  - Frampton CMA
AD  - Department of Medicine, University of Otago, Christchurch, New Zealand.
FAU - Atkinson, Hartley C
AU  - Atkinson HC
AD  - Drug Development, AFT Pharmaceuticals Ltd, Auckland, New Zealand, 
      phillip.aitken@aftpharm.com.
LA  - eng
PT  - Journal Article
DEP - 20190208
PL  - New Zealand
TA  - J Pain Res
JT  - Journal of pain research
JID - 101540514
PMC - PMC6371943
OTO - NOTNLM
OT  - multimodal pain management
OT  - nonsteroidal anti-inflammatory drugs
OT  - paracetamol
OT  - postoperative analgesia
OT  - surgical pain
COIS- Disclosure HA is a shareholder and Managing Director of AFT Pharmaceuticals Ltd. 
      IS and JZ are employees and shareholders of AFT Pharmaceuticals Ltd. PA and RP 
      are employees of AFT Pharmaceuticals Ltd. CMAF provides consultancy services to 
      AFT Pharmaceuticals Ltd. The authors report no other conflicts of interest in 
      this work.
EDAT- 2019/02/26 06:00
MHDA- 2019/02/26 06:01
PMCR- 2019/02/08
CRDT- 2019/02/27 06:00
PHST- 2019/02/27 06:00 [entrez]
PHST- 2019/02/26 06:00 [pubmed]
PHST- 2019/02/26 06:01 [medline]
PHST- 2019/02/08 00:00 [pmc-release]
AID - jpr-12-621 [pii]
AID - 10.2147/JPR.S189605 [doi]
PST - epublish
SO  - J Pain Res. 2019 Feb 8;12:621-634. doi: 10.2147/JPR.S189605. eCollection 2019.