}

Lansoprazole

Proton Pump Inhibitors

Drug Overview

Lansoprazole, sold under the brand name Prevacid among others, is a proton pump inhibitor that reduces the production of stomach acid.

It is indicated for gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome by suppressing excess gastric acid secretion.

Lansoprazole works by irreversibly inhibiting the H+/K+ ATPase enzyme (the proton pump) on gastric parietal cells, blocking the final step of acid production.

Relevant Genes and Their Roles

The primary gene influencing lansoprazole response is CYP2C19, a liver enzyme responsible for metabolizing many drugs, including proton pump inhibitors. Metabolism is the process by which the body breaks down medications into inactive compounds for elimination.

Variants in CYP2C19 can alter how quickly lansoprazole is cleared: some variants increase enzyme activity leading to rapid clearance, while others reduce activity resulting in slower drug breakdown. These differences impact drug levels, efficacy, and risk of side effects.

Impact of Genetics on Drug Response

CYP2C19 genotypes define metabolizer phenotypes that influence lansoprazole exposure: ultrarapid and rapid metabolizers clear the drug quickly and may experience reduced efficacy, intermediate and poor metabolizers clear it more slowly and have higher drug levels with increased efficacy and potential toxicity, while normal metabolizers exhibit typical responses.

Expected Clinical Effects of Genetic Variation

Ultrarapid and Rapid Metabolizers

  • Effect on drug levels: Lower plasma concentrations; faster clearance
  • Clinical consequence: Reduced efficacy; increased risk of treatment failure
  • Side effects: Similar to standard dosing; typically mild and infrequent

Normal Metabolizers

  • Effect on drug levels: Expected plasma concentrations within normal range
  • Clinical consequence: Standard efficacy; occasional need for higher dose in certain conditions
  • Side effects: Typical PPI side effects such as headache or gastrointestinal discomfort; usually mild

Intermediate Metabolizers

  • Effect on drug levels: Higher plasma concentrations; slower clearance
  • Clinical consequence: Increased efficacy; potential risk of dose-related toxicity
  • Side effects: Possible gastrointestinal symptoms or headache; mild to moderate

Poor Metabolizers

  • Effect on drug levels: Markedly elevated plasma concentrations; very slow clearance
  • Clinical consequence: Greater efficacy; higher risk of long-term toxicity
  • Side effects: Increased risk of headache, diarrhea, or abdominal pain; may be moderate

Indeterminate/Not Available

  • Effect: Unknown
  • Clinical consequence: No specific guidance; follow standard dosing with monitoring
  • Side effects: Unknown; use routine safety monitoring

Dosing Guidelines

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 the treatment of Helicobacter 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 the treatment of 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 / Not Available The impact of your genotype on response to this drug is unknown. Initiate therapy with recommended starting dose.

Alternative Treatment Options

No specific alternative drugs are recommended in the CPIC guideline. In cases of suboptimal response, other acid-suppressing therapies such as H2-receptor antagonists (e.g., famotidine, ranitidine) may be considered as examples.

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.

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