Dexlansoprazole

Dexlansoprazole (brand name Dexilant) is a proton pump inhibitor used to reduce gastric acid secretion. It belongs to a class of medications designed to treat acid-related disorders by targeting the final step of acid production in the stomach.

This drug is prescribed for conditions such as gastroesophageal reflux disease (GERD), erosive esophagitis, and as part of combination therapy to eradicate Helicobacter pylori infections. It helps relieve heartburn, acid regurgitation, and promotes healing of the esophageal lining.

Dexlansoprazole works by irreversibly inhibiting the H+/K+ ATPase enzyme (the gastric proton pump) in the stomach lining. By blocking this enzyme, it significantly decreases gastric acidity and allows damaged tissue to heal.

The primary gene impacting dexlansoprazole metabolism is CYP2C19, which encodes an enzyme in the liver responsible for oxidizing and clearing many proton pump inhibitors. CYP2C19 is part of the cytochrome P450 family of enzymes that metabolize drugs and other substances in the body.

Genetic variations in CYP2C19 can alter enzyme activity, leading to faster or slower breakdown of dexlansoprazole. A “metabolizer” refers to how efficiently your body processes a drug: ultrarapid and rapid metabolizers clear the drug more quickly, whereas intermediate and poor metabolizers clear it more slowly.

CYP2C19 genetic phenotypes affect dexlansoprazole plasma levels and therapeutic outcomes. Ultrarapid and rapid metabolizers often have lower drug concentrations, increasing the risk of treatment failure, while intermediate and poor metabolizers have higher concentrations, which can improve efficacy but may raise the risk of side effects.

The clinical impact of CYP2C19 variation ranges from reduced efficacy in fast metabolizers to increased exposure in slow metabolizers. Below are typical outcomes by phenotype group:

Ultrarapid Metabolizer

• Effect on drug levels: Significantly decreased plasma concentrations
• Clinical consequence: Increased risk of therapeutic failure and persistent acid symptoms
• Side effects: Generally fewer side effects due to lower exposure; severity and frequency are low

Rapid Metabolizer

• Effect on drug levels: Decreased plasma concentrations
• Clinical consequence: Higher chance of incomplete acid suppression and treatment failure
• Side effects: Mild and infrequent; lower overall exposure reduces side effect risk

Normal Metabolizer

• Effect on drug levels: Expected plasma concentrations in the normal range
• Clinical consequence: Standard efficacy; may require dose adjustment in certain conditions
• Side effects: Typical side effects such as headache or diarrhea; moderate frequency

Intermediate Metabolizer

• Effect on drug levels: Increased plasma concentrations compared with normal
• Clinical consequence: Potential for enhanced efficacy; moderate risk of toxicity with long-term use
• Side effects: Possible abdominal pain or headache; moderate severity, occasional occurrence

Poor Metabolizer

• Effect on drug levels: Significantly increased plasma concentrations
• Clinical consequence: Increased efficacy and higher chance of adverse effects over time
• Side effects: More pronounced side effects such as diarrhea or nausea; moderate to high frequency

Indeterminate / Not Available

• Effect: Unknown impact on drug levels
• Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring
• Side effects: Unable to predict; monitor patient response

CYP2C19 Dosing Guideline

Phenotype	Clinical Consequence	Guideline Recommendation
Ultrarapid Metabolizer	Your body clears the drug very quickly, so a higher dose is usually needed for the medicine to work properly.	Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.
Rapid Metabolizer	Your body clears the drug faster than average, so sometimes a higher dose is needed, especially for certain infections.	Initiate standard starting daily dose. Consider increasing dose by 50–100% for H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.
Normal Metabolizer	Your body processes the drug normally, but sometimes a higher dose is needed for certain conditions.	Initiate standard starting daily dose. Consider increasing dose by 50–100% for H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.
Likely Intermediate Metabolizer	Your body holds onto the drug longer, so you may need a lower dose over long-term use to avoid side effects.	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.
Intermediate Metabolizer	Your body holds onto the drug longer, so you may need a lower dose over long-term use to avoid side effects.	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.
Likely Poor Metabolizer	Your body processes the drug slowly, so a lower dose may be needed for long-term use to prevent side effects.	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.
Poor Metabolizer	Your body processes the drug slowly, so a lower dose may be needed for long-term use to prevent side effects.	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.
Indeterminate	Unknown impact	Initiate therapy with recommended starting dose.
Not available	Unknown impact	Initiate therapy with recommended starting dose.

No specific alternative treatment options are provided in the CPIC guideline for dexlansoprazole. Clinicians may consider other proton pump inhibitors such as esomeprazole or lansoprazole, which have different metabolic profiles, based on individual patient needs.

• CPIC – CPIC Guideline for Proton Pump Inhibitors and CYP2C19