Pravastatin

Pravastatin is a member of the statin class of drugs (HMG-CoA reductase inhibitors) and is marketed under the brand name Pravachol.

It is primarily used to treat hypercholesterolemia—elevated cholesterol levels in the blood—and to reduce the risk of cardiovascular events such as heart attacks and strokes.

Pravastatin works by inhibiting the HMG-CoA reductase enzyme in the liver, which decreases cholesterol synthesis and leads to increased clearance of low-density lipoprotein (LDL) cholesterol from the bloodstream.

The primary gene affecting pravastatin pharmacokinetics is SLCO1B1. This gene encodes the OATP1B1 transporter, a protein that moves pravastatin from the blood into liver cells for metabolism.

Variants in SLCO1B1 can alter transporter activity. Reduced‐function variants can slow hepatic uptake of pravastatin, leading to higher circulating drug levels, while increased‐function variants maintain normal uptake. A transporter is simply a protein that helps carry drugs into cells.

Individuals with SLCO1B1 variants that reduce or eliminate transporter function tend to have higher systemic exposure to pravastatin, which increases their risk of statin‐associated muscle symptoms (myopathy). Those with normal or increased transporter function usually experience standard pravastatin levels and typical risk profiles. Patients with indeterminate or unknown SLCO1B1 genotypes should be managed with conventional dosing and clinical monitoring.

Increased Function

• Effect on drug levels: Drug levels typically remain within expected range
• Clinical consequence: Standard risk of myopathy
• Side effects: Muscle pain or weakness is uncommon and similar to the general population

Normal Function

• Effect on drug levels: Drug levels typically remain within expected range
• Clinical consequence: Standard risk of myopathy
• Side effects: Muscle pain or weakness is uncommon and similar to the general population

Decreased Function

• Effect on drug levels: Slightly increased drug levels compared with normal
• Clinical consequence: Typical myopathy risk at standard doses, especially above 40 mg
• Side effects: Mild muscle symptoms may occur; uncommon

Possible Decreased Function

• Effect on drug levels: Slightly increased drug levels compared with normal
• Clinical consequence: Typical myopathy risk at standard doses, especially above 40 mg
• Side effects: Mild muscle symptoms may occur; uncommon

Poor Function

• Effect on drug levels: Significantly increased drug exposure
• Clinical consequence: Elevated risk of myopathy even at lower doses
• Side effects: Higher likelihood of muscle pain; moderate severity, may require dose reduction

Possible Poor Function

• Effect on drug levels: Significantly increased drug exposure
• Clinical consequence: Elevated risk of myopathy even at lower doses
• Side effects: Higher likelihood of muscle pain; moderate severity, may require dose reduction

Indeterminate/Not Available

• Effect: Unknown
• Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring

SLCO1B1 Dosing Guideline

Phenotype	Clinical Consequence	Guideline Recommendation
Increased Function	Typical myopathy risk and pravastatin exposure	Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines.
Normal Function	Typical myopathy risk and pravastatin exposure	Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines.
Decreased Function	Increased pravastatin exposure compared with normal function; typical myopathy risk with doses ≤40 mg	Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially with doses >40 mg per day.
Possible Decreased Function	Increased pravastatin exposure compared with normal function; typical myopathy risk with doses ≤40 mg	Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially with doses >40 mg per day.
Poor Function	Increased pravastatin exposure compared with normal and decreased function; typical myopathy risk with doses ≤40 mg	Prescribe ≤40 mg as a starting dose and adjust doses of pravastatin based on disease-specific guidelines. If patient is tolerating 40-mg dose but higher potency is needed, a higher dose (>40 mg) or an alternative statin or combination therapy could be considered. Prescriber should be aware of possible increased risk for myopathy especially with pravastatin doses >40 mg.
Possible Poor Function	Increased pravastatin exposure compared with normal and decreased function; typical myopathy risk with doses ≤40 mg	Prescribe ≤40 mg as a starting dose and adjust doses of pravastatin based on disease-specific guidelines. If patient is tolerating 40-mg dose but higher potency is needed, a higher dose (>40 mg) or an alternative statin or combination therapy could be considered. Prescriber should be aware of possible increased risk for myopathy especially with pravastatin doses >40 mg.
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.

Examples of alternative statins or approaches mentioned in the CPIC guidelines include using a different statin such as atorvastatin or simvastatin, or combining pravastatin with non-statin lipid-lowering therapies when higher potency is needed. These are examples from CPIC guidelines, not medical advice.

• CPIC – CPIC Guideline for Statins