Piroxicam Therapy and CYP2C9 Genotype

Excerpt

Piroxicam (brand name Feldene) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat osteoarthritis and rheumatoid arthritis. Piroxicam provides pain relief and reduces inflammation.

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

Like all NSAIDs, piroxicam 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 standard dose of piroxicam for osteoarthritis and rheumatoid arthritis in adults is 20 mg once daily. But for all patients, the lowest effective dose of piroxicam should be used for the shortest length of time, consistent with the treatment goals of each individual (1).

The FDA-approved drug label for piroxicam states that a dose reduction should be considered in “patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin and phenytoin)”. Dose reductions should be considered because these patients may have abnormally high plasma levels of piroxicam caused by reduced metabolic clearance. However, specific dose reductions based on CYP2C9 phenotype are not provided (Table 1) (1).

As for all NSAIDs, piroxicam is contraindicated in patients with a known hypersensitivity, a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or another NSAID, and following coronary artery bypass graft (CABG) surgery. Piroxicam should also be avoided by pregnant women starting at 30 weeks gestation.