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Pitavastatin

Cholesterol Medications

Drug Overview

Pitavastatin, marketed under the brand name Livalo, is a prescription medication belonging to the statin class. Statins are widely used to lower harmful low-density lipoprotein (LDL) cholesterol levels in the blood and help prevent cardiovascular events such as heart attack and stroke.

This drug is primarily prescribed for adults with primary hyperlipidemia or mixed dyslipidemia, and in some cases to reduce cardiovascular risk in patients with elevated cholesterol. By lowering LDL-cholesterol, pitavastatin contributes to slowing the progression of atherosclerosis and reducing coronary heart disease risk.

Pitavastatin works by inhibiting HMG-CoA reductase, the liver enzyme responsible for the rate-limiting step in cholesterol synthesis. This inhibition decreases cholesterol production, increases LDL receptors on hepatocytes, and enhances clearance of LDL from the bloodstream.

Relevant Genes and Their Roles

The key gene affecting pitavastatin response is SLCO1B1, which encodes the liver transporter protein OATP1B1 (organic anion-transporting polypeptide 1B1). This transporter controls the uptake of pitavastatin from the blood into liver cells, where the drug exerts its cholesterol‐lowering effect.

Genetic variations in SLCO1B1 can alter transporter function. A variant that reduces OATP1B1 activity may lead to higher pitavastatin levels in the bloodstream (and increased risk of muscle toxicity), while variants that enhance function may lower systemic levels. Understanding these variants helps guide dosing and reduce adverse effects.

Impact of Genetics on Drug Response

SLCO1B1 phenotype groups—ranging from increased to poor function—determine how quickly pitavastatin is taken up into the liver, influencing systemic drug exposure and myopathy risk. Patients with reduced transporter function exhibit higher drug levels and an elevated chance of muscle‐related side effects, while those with increased function have typical exposure and standard risk.

Expected Clinical Effects of Genetic Variation

Ultra-rapid/Rapid (Increased Function)

  • Effect: Normal pitavastatin exposure
  • Clinical consequence: Standard cholesterol lowering and typical myopathy risk
  • Side effects: No increased muscle‐related side effects; frequency similar to general population

Normal (Normal Function)

  • Effect: Normal pitavastatin exposure
  • Clinical consequence: Standard cholesterol lowering and typical myopathy risk
  • Side effects: No increased muscle‐related side effects; common frequency

Intermediate (Decreased/Possible Decreased Function)

  • Effect: Moderately increased pitavastatin exposure
  • Clinical consequence: Higher-than-usual myopathy risk
  • Side effects: Mild to moderate muscle‐related side effects; possible increase in incidence

Poor (Poor/Possible Poor Function)

  • Effect: Substantially increased pitavastatin exposure
  • Clinical consequence: Elevated myopathy risk
  • Side effects: Potential for severe muscle‐related side effects; uncommon but more serious when they occur

Indeterminate/Not available

  • Effect: Unknown
  • Clinical consequence: No specific guidance; use standard dosing with monitoring
  • Side effects: Unknown frequency or severity

Dosing Guidelines

The following dosing guidelines are based on the available guidelines for pitavastatin and SLCO1B1 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 based on disease‐specific guidelines.
Normal Function Normal myopathy risk Prescribe desired starting dose and adjust based on disease‐specific guidelines.
Decreased Function Increased pitavastatin exposure; may translate to increased myopathy risk Start ≤2 mg, adjust per guidelines; for doses >2 mg consider alternative statins (e.g., atorvastatin 10–20 mg, pravastatin 40 mg, rosuvastatin 5–10 mg) or combination therapy.
Possible Decreased Function Increased pitavastatin exposure; may translate to increased myopathy risk Start ≤2 mg, adjust per guidelines; for doses >2 mg consider alternative statins (e.g., atorvastatin 10–20 mg, pravastatin 40 mg, rosuvastatin 5–10 mg) or combination therapy.
Poor Function Increased exposure vs. normal and decreased; higher myopathy risk Start ≤1 mg, adjust per guidelines; if higher dose needed, switch to alternative statin or use combination therapy.
Possible Poor Function Increased exposure vs. normal and decreased; higher myopathy risk Start ≤1 mg, adjust per guidelines; if higher dose needed, switch to alternative statin or use 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

Based on the CPIC guideline, alternative statins with lower myopathy risk include:

  • Atorvastatin (10–20 mg)
  • Pravastatin (40 mg)
  • Rosuvastatin (5–10 mg)

These are examples from the guideline and not individual 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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