Flurbiprofen Therapy and CYP2C9 Genotype

Review
In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012.
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Excerpt

Flurbiprofen (brand name Ansaid) is a nonsteroidal anti-inflammatory drug (NSAID). Tablets and skin patches are used in the management of osteoarthritis and rheumatoid arthritis. Flurbiprofen provides pain relief and reduces inflammation. Flurbiprofen eye drops (brand name Ocufen) may also be used to prevent miosis (excessive constriction of the pupil) during eye operations; e.g., cataract surgery.

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

Like all NSAIDs, flurbiprofen increases the risk of serious cardiovascular events, including myocardial infarction and stroke, and serious gastrointestinal (GI) adverse events such as bleeding, ulceration, and perforation, which may be fatal.

The recommended starting dose of flurbiprofen tablets in adults is 200–300 mg per day, divided for administration 2, 3, or 4 times a day. But for all patients, the lowest effective dose of flurbiprofen should be used for the shortest length of time, consistent with the treatment goals of each individual.

The FDA-approved drug label for flurbiprofen states that the dose of flurbiprofen should be reduced 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)” (Table 1). This dose reduction is to avoid the abnormally high plasma levels of flurbiprofen in these patients caused by reduced metabolic clearance. However, specific dose reductions based on CYP2C9 phenotype are not provided (1).

As for all NSAIDs, flurbiprofen 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 for coronary artery bypass graft (CABG) surgery. Flurbiprofen should also be avoided by pregnant women starting at 30 weeks gestation (1).

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