Piroxicam

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) marketed under the brand name Feldene. It is a long-acting agent used to manage pain and inflammation.

This medication is commonly prescribed for osteoarthritis, rheumatoid arthritis, and other musculoskeletal disorders. By reducing inflammation and alleviating pain, piroxicam helps improve mobility and quality of life.

Piroxicam works by inhibiting cyclooxygenase enzymes (COX-1 and COX-2), which in turn decreases the production of prostaglandins, the compounds responsible for pain and swelling in inflamed tissues.

Genetic variation in the CYP2C9 gene is most relevant for piroxicam. CYP2C9 encodes an enzyme in the liver that metabolizes many NSAIDs, including piroxicam.

CYP2C9 converts piroxicam into inactive metabolites. Variants in this gene can slow or speed up metabolism, affecting how quickly the drug is cleared from the body. Metabolizer categories range from poor to normal to ultra-rapid, defining the enzyme’s activity level.

Individuals with reduced CYP2C9 activity (intermediate or poor metabolizers) clear piroxicam more slowly, leading to higher blood levels and risk of toxicity. Normal metabolizers process the drug at expected rates, while those with indeterminate genotypes follow standard dosing until more data are available.

The clinical effects of CYP2C9 variation on piroxicam response are categorized by metabolizer status:

Normal Metabolizer

• Effect on drug levels: Standard clearance, typical blood concentrations
• Clinical consequence: Expected therapeutic response with standard dose
• Side effects: Typical NSAID risks (gastrointestinal discomfort, renal effects); no increased severity beyond standard profile

Intermediate Metabolizer

• Effect on drug levels: Mildly to moderately reduced clearance, slightly elevated concentrations
• Clinical consequence: Possible increased exposure; monitoring for adverse effects may be warranted
• Side effects: Slightly higher risk of gastrointestinal or renal side effects; severity generally mild to moderate

Poor Metabolizer

• Effect on drug levels: Significantly reduced clearance, prolonged half-life, high plasma concentrations
• Clinical consequence: Increased risk of toxicity, including gastrointestinal bleeding or renal impairment
• Side effects: Higher frequency and severity of NSAID-related adverse effects; close monitoring or alternative therapy advised

Indeterminate/Not Available

• Effect on drug levels: Unknown impact
• Clinical consequence: No specific guidance; follow standard dosing with careful clinical monitoring
• Side effects: Assess and manage according to patient tolerance and clinical response

CYP2C9 Dosing Guideline

Examples of alternative therapies include NSAIDs that are less dependent on CYP2C9 for clearance (e.g., ibuprofen, diclofenac) or agents with shorter half-lives. These options are provided as examples from CPIC guidelines and not medical advice.

• CPIC – Guideline for NSAIDs Based on CYP2C9 Genotype
• FDA – Table of Pharmacogenetic Associations