Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC) analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs) including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug–drug interactions (DDIs) between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available.

Keywords:

• adverse effects
• nonsteroidal anti-inflammatory drugs
• gastrointestinal
• cardiovascular
• renal

Acknowledgments

Editorial/medical writing support was provided by John O’Flaherty, PhD, of ProEd Communications, Inc., and Lauren Cerruto and John H Simmons, MD, of Peloton Advantage, LLC, and was funded by Pfizer Inc.

Disclosure

Nicholas Moore is an employee of Bordeaux University and Bordeaux University Hospital. The department he heads has 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, GlaxoSmith-Kline, Grunenthal, 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). Dr Moore has acted as a consultant for AstraZeneca, Aventis, Baxter, Boots, GlaxoSmithKline, Helsinn, Novartis, Pfizer, Reckitt Benckiser, Roche, and other pharmaceutical companies. He holds no stock or other financial interest in any pharmaceutical company. Charles Pollack and Paul Butkerait are employees of Pfizer Consumer Healthcare. The authors report no other conflicts of interest in this work.