Prescriber Update Articles

Reducing the risk of GI reactions with NSAIDs and/or COX-2 inhibitors

Website: December 2010
Prescriber Update 2010; 31(4):32

Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) have varying degrees of anti­inflammatory, analgesic and antipyretic effects. These effects are related to the inhibition of the cyclo-oxygenase isoenzymes COX-1 or COX-2 that are involved in the production of prostaglandins and thromboxanes.¹

Gastrointestinal (GI) side effects occur commonly with all NSAIDs, including selective COX-2 inhibitors. These events are generally considered to be mediated by inhibition of COX-1, responsible for synthesis of the prostaglandins that inhibit acid secretion.¹ COX-2 selectivity should theoretically reduce the risk of GI adverse events; however studies have shown that COX-2 inhibitors still have a low affinity for COX-1.²

An analysis of reports sent to the Centre for Adverse Reactions (CARM) shows most patients experiencing GI adverse reactions with NSAIDs or COX-2 inhibitors had other risk factors for these events. Risk factors include: age greater than 65 years, history of peptic ulcer or gastrointestinal bleeding, previous gastric irritation with NSAID use, use of multiple NSAIDs or COX-2 inhibitors, and concomitant use of corticosteroids, anticoagulants and SSRIs.

For all patients requiring treatment with either a non-selective NSAID or COX-2 inhibitor, the extent and severity of gastrointestinal events can be reduced by:

• Using the lowest effective dose for the shortest duration possible.
• Avoiding the concomitant use of more than one NSAID, or a NSAID with a COX-2 inhibitor.
• Avoiding the concomitant use of aspirin and/ or an anticoagulant where possible. If such a combination is necessary, a gastro-protective agent such as a proton pump inhibitor should be considered.
• Informing patients of, and monitoring for, signs and symptoms of gastrointestinal adverse events.
• Identifying patients with risk factors for serious GI adverse events and considering the use of a gastro-protective agent such as a proton pump inhibitor.

Healthcare professionals are encouraged to keep up-to-date with current prescribing information in product data sheets and applicable guidelines.

References:

1. Rang H., Dale M. and Ritter J. 1999. Pharmacology (4th Ed.) Edinburgh: Churchill Livingstone.
2. Pfizer New Zealand Ltd. 5 June 2009. Celebrex (celecoxib) data sheet. http://www.medsafe.govt.nz/profs/Datasheet/c/Celebrexcap.pdf