Gastrointestinal safety and tolerability of oral non-aspirin over-the-counter analgesics

ABSTRACT

Over-the-counter (OTC) analgesics are routinely used worldwide for self-management of various painful conditions. Despite this, there has been little in-depth review of the safety of non-aspirin analgesics at OTC doses. This paper reviews the available literature on the gastrointestinal (GI) and hepatic safety of non-aspirin OTC analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs; ibuprofen, ketoprofen, diclofenac, and naproxen) and acetaminophen; safety in overdose is also reviewed. Each non-aspirin OTC analgesic has a distinct adverse event (AE) profile, with GI AE rates for OTC dosing in one study ranging from 37% for diclofenac to 7.2% for ibuprofen and 7.6% for acetaminophen; GI effects accounted for 75% of total AEs in the study. Across all studies reviewed here, the risk of serious GI toxicity, including upper GI bleeding and peptic ulcers, was low at OTC doses. By contrast, while both NSAIDs and acetaminophen may be associated with hepatotoxicity and acute liver failure (ALF), the risks associated with acetaminophen are somewhat higher and better documented. Reports of NSAID-associated hepatotoxicity rarely make distinctions by dose, making the risk at OTC doses difficult to assess. Liver injury due to acetaminophen, however, can occur at doses < 4000 mg. Case reports of NSAID-associated overdose are rare, while acetaminophen-containing drugs are a leading cause of overdose and are implicated in up to 97% of ALFs leading to transplant involving overdose. OTC analgesics are effective for self-management of pain; however, they are associated with a low but important rate of GI and hepatic events, as well as a risk of intentional and non-intentional overdose. Given the widespread use of this class of drugs, it is important for healthcare professionals to be mindful of their patients’ use of OTC analgesics.

KEYWORDS:

• Acetaminophen
• diclofenac
• gastrointestinal safety
• hepatic safety
• ibuprofen
• ketoprofen
• over-the-counter
• overdose

Acknowledgments

Medical writing support was provided by John H. Simmons, MD, of Peloton Advantage, LLC, and was funded by Pfizer.

Declaration of Interest

NM is an employee of Bordeaux University and Bordeaux University Hospital. The department he heads has over the years worked or is working with or has received funds from Abbott Laboratories, ADDS, AFRETH, Aptalis, Arkopharma, Asahi, AstraZeneca, Aventis, Axcan, Baxter, Bayer, Berkem, Bial, BioAlliance, Biopharma, BMS, BNIA, Boehringer Ingelheim, Boots, Caviar de France, Chaine Thermale du Soleil, Celgene, Cephalon, Daiichi Sankyo, Eli Lilly and Company, Ethicon, Eugénie-les-Bains, Expanscience, Génévrier, Genopharm, GlaxoSmithKline, Grünenthal, Guerbet, Helsinn, Horus Pharma, I3, Innothera, Ipsen, Janssen-Cilag, Johnson & Johnson, Leo Pharma, Lundbeck, Meda Pharmaceuticals, Medtronic, Merck & Co, Merck Serono, Norgine, Novartis, Novartis Family Health, Novo Nordisk, Nycomed, Orion Corporation, Pfizer, Pfizer FHC, Pierre Fabre, Procter and Gamble, Reckitt Benckiser, Roche, Sanofi, Schering-Plough, Servier, Stallergènes, Takeda, Teva, UCB, Vivalis, Vivatec, Warner Chilcott, Wyeth, and Xanodyne Pharmaceuticals. In addition, public funding for specific projects has been received from the Seventh Framework Program (FP7 [EU]), European Medicines Agency, French Agency for the Safety of Health Products (AFSSAPS), National Agency for the Safety of Medicines and Health Products (MSNA), Directorate General of the Supply of Care (DGOS), French National Authority for Health (HAS), Clinical Research Hospital Program (PHRC), Interregional Delegation of Clinical Research (DIRC), Delegation of Clinical Research and Innovation (DRCi), and University Hospital Center (CHU). JMS currently serves as a consultant for Aralez Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial interests or otherwise to disclose.

Additional information

Funding

This manuscript was funded by Pfizer.