Celecoxib Therapy and CYP2C9 Genotype

Excerpt

Celecoxib (brand name Celebrex) is a nonsteroidal anti-inflammatory drug (NSAID) that is used to manage osteoarthritis, rheumatoid arthritis, menstrual symptoms, and acute pain.

Celecoxib is a “COX-2 inhibitor.” The cyclooxygenase (COX) enzymes catalyze pathways that play a key role in the generation of the inflammatory response. Most NSAIDs inhibit both types of cyclooxygenase, COX-1 and COX-2, while celecoxib selectively inhibits COX-2.

Celecoxib is primarily metabolized by CYP2C9. Individuals who lack CYP2C9 activity (“CYP2C9 poor metabolizers”) have an increased exposure to celecoxib, and an increased risk of side effects.

Like all non-aspirin NSAIDs, celecoxib increases the risk of serious cardiovascular events, including myocardial infarction and stroke, and serious gastrointestinal (GI) adverse events such as bleeding, ulceration, and perforation.

The FDA-approved drug label states that in individuals “who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin), initiate treatment with half the lowest recommended dose” (Table 1)(1). Recommendations from the Clinical Pharmacogenetics Implementation Consortium (CPIC) include initiating celecoxib at 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution” (Table 2) (2).