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Flurbiprofen response

MedGen UID:
941175
Concept ID:
CN258139
Sign or Symptom
Synonyms: Ansaid response; Ocufen response
Drug:
flurbiprofen
MedGen UID:
4747
Concept ID:
C0016377
Pharmacologic Substance
A derivative of propionic acid, and a phenylalkanoic acid derivative of non-steroidal antiinflammatory drugs (NSAIDs) with analgesic, antiinflammatory and antipyretic effects. Flurbiprofen non-selectively binds to and inhibits cyclooxygenase (COX). This results in a reduction of arachidonic acid conversion into prostaglandins that are involved in the regulation of pain, inflammation and fever. This NSAID also inhibits carbonic anhydrase, thereby reducing the production of hydrogen and bicarbonate ions. Upon ocular administration, flurbiprofen may reduce bicarbonate ion concentrations leading to a decrease in the production of aqueous humor, thereby lowering intraocular pressure. [from NCI]
 
Gene (location): CYP2C9 (10q23.33)

Definition

Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are among the most commonly prescribed drugs to treat pain, fever and inflammation. The main therapeutic effect of NSAIDs occurs via blocking the production of prostaglandin that cause inflammation. Hepatic metabolism by cytochrome P450 isoforms CYP2C9, 1A2, and 3A4, and renal excretion are the principal routes of clearance of the majority of NSAIDs. Genetic variants in CYP2C9 (e.g., CYP2C9*2 and *3), along with other genetics and clinical factors, have been shown to affect systemic plasma concentrations of NSAIDs and potentially safety. Patients with CYP2C9 decreased or no function alleles may have elevated exposure and at increased risk for adverse effects. Guidelines regarding the use of pharmacogenomic tests in dosing for NSAIDs have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. The CPIC guideline provides specific therapeutic recommendations for a number of NSAIDs (celecoxib, flurbiprofen, ibuprofen, lornoxicam, meloxicam, piroxicam and tenoxicam) based on CYP2C9 genotype. [from PharmGKB]

Additional description

From Medical Genetics Summaries
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)". 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. 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.  https://www.ncbi.nlm.nih.gov/books/NBK537365

Professional guidelines

PubMed

Santini M, Da Rosa RA, Ferreira MB, Barletta F, Longo do Nascimento A, Weissheimer T, Estrela C, So MV
Eur Endod J 2021 Apr;6(1):15-24. Epub 2021 Feb 2 doi: 10.14744/eej.2020.85856. PMID: 33609020Free PMC Article
Rodrigues EB, Farah ME, Bottós JM, Bom Aggio F
Dev Ophthalmol 2016;55:212-20. Epub 2015 Oct 26 doi: 10.1159/000431197. PMID: 26502088
Marmura MJ, Silberstein SD, Schwedt TJ
Headache 2015 Jan;55(1):3-20. doi: 10.1111/head.12499. PMID: 25600718

Curated

DailyMed Drug Label, FLURBIPROFEN, 2021

DailyMed Drug Label, flurbiprofen, 2016

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted 1 information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2017 Statement from the US Food and Drug Administration (FDA)

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), reduce the dose of flurbiprofen to avoid abnormally high plasma levels due to reduced metabolic clearance.

Please review the complete therapeutic recommendations that are located here: (1)

1 The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug.

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