}

Ibuprofen

Pain Management

Drug Overview

Ibuprofen, known by the brand name Advil among others, is a widely used nonsteroidal anti-inflammatory drug (NSAID) that helps relieve pain, reduce inflammation, and lower fever. It is available over-the-counter and by prescription in various formulations.

It is commonly used to treat conditions such as headaches, menstrual cramps, muscle aches, arthritis, and dental pain. By inhibiting cyclooxygenase (COX) enzymes, ibuprofen decreases the synthesis of prostaglandins, which are mediators of pain and inflammation.

Specifically, ibuprofen nonselectively inhibits both COX-1 and COX-2 enzymes in the body, leading to reduced production of prostaglandins and ultimately diminishing pain signals, swelling, and fever.

Relevant Genes and Their Roles

Ibuprofen is primarily metabolized by the liver enzyme CYP2C9, a member of the cytochrome P450 family. CYP2C9 helps chemically alter drugs so they can be more easily eliminated from the body through urine or bile.

Genetic variants in CYP2C9 can lead to differences in enzyme activity. “Metabolism” refers to how quickly or slowly the body breaks down a drug: if metabolism is reduced, drug levels may stay higher for longer, while increased metabolism may clear the drug too fast.

Impact of Genetics on Drug Response

Variation in the CYP2C9 gene can categorize individuals into different metabolizer phenotypes—normal, intermediate, poor, or indeterminate. Poor metabolizers clear ibuprofen more slowly, increasing risk of side effects such as gastrointestinal bleeding or renal impairment, whereas intermediate metabolizers have moderately reduced clearance, and normal metabolizers handle standard dosing as expected.

Expected Clinical Effects of Genetic Variation

Normal Metabolizer

  • Effect on drug levels: Standard clearance; drug levels as expected.
  • Clinical consequence: Typical pain relief with standard dosing.
  • Side effects: Common NSAID side effects (e.g., mild gastrointestinal upset), frequency <5%.

Intermediate Metabolizer

  • Effect on drug levels: Moderately slower metabolism; slightly higher drug levels.
  • Clinical consequence: May experience enhanced effect or mild increased risk of side effects with standard dose.
  • Side effects: Mild gastrointestinal or renal effects, low to moderate frequency.

Poor Metabolizer

  • Effect on drug levels: Significantly reduced clearance; elevated drug concentrations.
  • Clinical consequence: Greater risk of toxicity and side effects at standard doses.
  • Side effects: Increased risk of serious gastrointestinal bleeding or kidney injury; severity moderate to high, frequency low.

Indeterminate/Not available

  • Effect: Unknown
  • Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring.

Dosing Guidelines

The following dosing guidelines are based on the available CPIC recommendations for CYP2C9 genotype in patients taking ibuprofen.

CYP2C9 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Normal Metabolizer Your body processes this drug normally, so the usual starting dose applies. Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
Intermediate Metabolizer (activity score 1.5) Your body slows the drug down slightly, but usually the normal starting dose is fine. Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
Intermediate Metabolizer (activity score 1.0) Your body slows the drug noticeably, so you should start at a lower dose and increase carefully if needed. Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events, such as blood pressure and kidney function.
Poor Metabolizer Your body processes the drug very slowly, so you should start at a much lower dose, increase carefully, or use a different drug. Initiate therapy with 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady‐state is reached (at least 5 days for ibuprofen). Carefully monitor adverse events such as blood pressure and kidney function. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.
Indeterminate / Not available The impact of your genotype on response to this drug is unknown. Initiate therapy with recommended starting dose.

Alternative Treatment Options

Examples of alternative treatment options include using analgesics that are not primarily metabolized by CYP2C9, such as acetaminophen, or selecting NSAIDs with minimal CYP2C9 involvement (e.g., celecoxib, lornoxicam). These are examples from guidelines and should not be taken as direct medical advice.

Sources and References

Disclaimer: This document is for informational purposes only and is not a substitute for medical advice. Clinical decisions should be made by a qualified healthcare professional.

Interested in learning more about how your genetics may affect your response to medication? Get started with Gene2Rx today.

I'm Interested