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Fluvastatin

Cholesterol Medications

Drug Overview

Fluvastatin is a member of the statin class of drugs and is marketed under the brand name Lescol. It acts as an HMG-CoA reductase inhibitor, which is the rate-limiting enzyme in cholesterol biosynthesis.

This medication is primarily used to lower elevated cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), and to reduce the risk of cardiovascular events such as heart attack and stroke in patients with hypercholesterolemia or mixed dyslipidemia.

By inhibiting HMG-CoA reductase in the liver, fluvastatin decreases cholesterol synthesis, leading to upregulation of LDL receptors on hepatocytes. This results in increased clearance of LDL cholesterol from the bloodstream.

Relevant Genes and Their Roles

Two key genes influence fluvastatin pharmacokinetics: SLCO1B1 and CYP2C9. SLCO1B1 encodes the OATP1B1 transporter, which mediates uptake of statins into the liver for metabolism and elimination. CYP2C9 is a liver enzyme responsible for oxidative metabolism of fluvastatin.

Variation in SLCO1B1 can alter how much drug enters liver cells, affecting systemic exposure. Changes in CYP2C9 activity influence how quickly fluvastatin is broken down. “Transporter” refers to a protein that moves drugs into cells, while “metabolizer” describes how well an enzyme processes a medication.

Impact of Genetics on Drug Response

Genetic variations in SLCO1B1 and CYP2C9 result in different metabolizer or function groups—ultra-rapid/rapid, normal, intermediate, and poor. Individuals with decreased transporter or enzyme function tend to have higher fluvastatin plasma levels, increasing the risk of muscle toxicity, while those with increased function may have lower levels and reduced efficacy.

Expected Clinical Effects of Genetic Variation

Ultra-Rapid/Rapid Metabolizers

  • Effect on drug levels: Lower than expected plasma concentrations
  • Clinical consequence: Potential reduced cholesterol-lowering efficacy
  • Side effects: Lower risk of muscle-related side effects; infrequent mild symptoms

Normal Metabolizers

  • Effect on drug levels: Expected therapeutic concentrations
  • Clinical consequence: Standard efficacy in lowering LDL cholesterol
  • Side effects: Typical risk of myalgia; mild to moderate muscle aches occasionally

Intermediate Metabolizers

  • Effect on drug levels: Moderately increased plasma concentrations
  • Clinical consequence: Slightly higher risk of myopathy, may require dose adjustment
  • Side effects: Mild to moderate muscle pain; occurs in some patients

Poor Metabolizers

  • Effect on drug levels: Markedly elevated plasma concentrations
  • Clinical consequence: High risk of muscle toxicity (myopathy, rarely rhabdomyolysis)
  • Side effects: Severe muscle pain and weakness; infrequent but potentially serious

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 guidelines for fluvastatin from the Clinical Pharmacogenetics Implementation Consortium (CPIC).

SLCO1B1 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Increased Function Normal myopathy risk Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines.
Normal Function Normal myopathy risk Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines.
Decreased Function Increased fluvastatin exposure; typical myopathy risk at ≤40 mg Prescribe desired starting dose; prescriber should be aware of possible increased risk for myopathy especially for doses >40 mg/day.
Possible Decreased Function Increased fluvastatin exposure; typical myopathy risk at ≤40 mg Prescribe desired starting dose; prescriber should be aware of possible increased risk for myopathy especially for doses >40 mg/day.
Poor Function Markedly increased exposure; typical myopathy risk at ≤40 mg Start at ≤40 mg/day. If higher potency needed, consider alternative lower-risk statin (e.g., atorvastatin 10–20 mg, pravastatin 40 mg, rosuvastatin 5–10 mg) or combination therapy.
Possible Poor Function Markedly increased exposure; typical myopathy risk at ≤40 mg Start at ≤40 mg/day. If higher potency needed, consider alternative lower-risk statin (e.g., atorvastatin 10–20 mg, pravastatin 40 mg, rosuvastatin 5–10 mg) or combination therapy.
Indeterminate No CPIC guidance for this phenotype Initiate therapy with recommended starting dose.
Not available No CPIC guidance for this phenotype Initiate therapy with recommended starting dose.

CYP2C9 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Normal Metabolizer Normal fluvastatin exposure Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines.
Intermediate Metabolizer Increased exposure; higher myopathy risk Start at ≤40 mg/day. If >40 mg needed, consider alternative statin or combination therapy.
Poor Metabolizer Markedly increased exposure; higher myopathy risk Start at ≤20 mg/day. If >20 mg needed, consider alternative statin or combination therapy.
Indeterminate No CPIC guidance for this phenotype Initiate therapy with recommended starting dose.
Not available No CPIC guidance for this phenotype Initiate therapy with recommended starting dose.

Alternative Treatment Options

Examples of alternative lower-risk statins cited in the guidelines include atorvastatin (10–20 mg), pravastatin (40 mg), and rosuvastatin (5–10 mg). These are provided for educational purposes only and do not constitute 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.

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