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Lovastatin

Cholesterol Medications

Drug Overview

Lovastatin, marketed under the brand name Mevacor, is a member of the statin class of cholesterol-lowering medications. It is prescribed to reduce elevated levels of low-density lipoprotein (LDL) cholesterol and to lower the risk of cardiovascular events.

This drug is used to treat primary hypercholesterolemia, mixed dyslipidemia, and to prevent coronary heart disease. Lovastatin works by inhibiting HMG-CoA reductase—the key enzyme in hepatic cholesterol synthesis—leading to decreased cholesterol production in the liver and increased clearance of LDL cholesterol from the bloodstream.

Relevant Genes and Their Roles

The primary gene affecting lovastatin response is SLCO1B1, which encodes the organic anion transporting polypeptide 1B1 (OATP1B1) protein. OATP1B1 is a liver uptake transporter that carries statin molecules from the blood into hepatocytes, where they exert their cholesterol-lowering effect.

Variations in SLCO1B1 can alter transporter activity: reduced-function variants cause less uptake into the liver, increasing blood concentrations and risk of muscle toxicity; increased-function variants can enhance uptake and reduce circulating levels. A transporter is a protein that moves substances across cell membranes to help drugs reach their target sites.

Impact of Genetics on Drug Response

Genetic variants in SLCO1B1 define phenotypes—ranging from increased to poor function—that influence how much lovastatin reaches the liver versus remains in the bloodstream. Individuals with decreased or poor function phenotypes have higher plasma concentrations of the drug and a greater risk of muscle-related side effects, while those with increased or normal function generally exhibit standard response and safety profiles.

Expected Clinical Effects of Genetic Variation

Ultra-rapid/Rapid (Increased Function)

  • Effect on drug levels: Enhanced hepatic uptake, leading to slightly lower plasma levels.
  • Clinical consequence: Standard cholesterol-lowering response.
  • Side effects: Typical statin-associated muscle symptoms (mild myalgia), infrequent.

Normal Function

  • Effect on drug levels: Normal distribution between plasma and liver.
  • Clinical consequence: Expected cholesterol reduction with standard dosing.
  • Side effects: Standard risk of muscle pain (mild, occasional).

Intermediate Function

  • Effect on drug levels: Moderately reduced hepatic uptake, resulting in elevated plasma concentrations.
  • Clinical consequence: Increased risk of muscle-related side effects.
  • Side effects: Muscle aches or weakness (moderate severity, occasional).

Poor Function

  • Effect on drug levels: Greatly reduced hepatic uptake, causing high plasma levels.
  • Clinical consequence: High risk of myopathy and potential rhabdomyolysis.
  • Side effects: Severe muscle toxicity (rare but serious).

Indeterminate/Not Available

  • Effect: Unknown impact on drug levels.
  • Clinical consequence: No specific guidance; standard dosing and monitoring recommended.

Dosing Guidelines

The following dosing guidelines are based on the available guidelines for lovastatin from CPIC.

SLCO1B1 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Increased Function Normal myopathy risk Prescribe desired starting dose and adjust doses of lovastatin based on disease-specific guidelines.
Normal Function Normal myopathy risk Prescribe desired starting dose and adjust doses of lovastatin based on disease-specific guidelines.
Decreased Function Increased lovastatin acid exposure, higher myopathy risk Consider prescribing a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg). If lovastatin is warranted, limit dose to ≤20 mg/day.
Possible Decreased Function Increased lovastatin acid exposure, higher myopathy risk Consider prescribing a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg). If lovastatin is warranted, limit dose to ≤20 mg/day.
Poor Function Increased lovastatin acid exposure, highest myopathy risk Consider prescribing a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg) instead of lovastatin.
Possible Poor Function Increased lovastatin acid exposure, highest myopathy risk Consider prescribing a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg) instead of lovastatin.
Indeterminate No CPIC guidance Initiate therapy with recommended starting dose.
Not available No CPIC guidance Initiate therapy with recommended starting dose.

Alternative Treatment Options

For individuals with decreased, possible decreased, poor, or possible poor SLCO1B1 function, CPIC guidelines suggest considering lower-risk statin alternatives such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg). If lovastatin is necessary, limit the dose to ≤20 mg/day to reduce the risk of muscle-related side effects. These examples are drawn from CPIC guidance and are not 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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