LESCOL XL® (fluvastatin sodium)
Description
Lescol XL® (fluvastatin sodium; Novartis Pharmaceuticals Corporation) is a newly released dosage and formulation of Lescol®. Lescol® was the first synthetic HMG‐CoA reductase inhibitor used in the treatment of hypercholesterolemia.
Indications
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Lescol XL® is to be used in conjunction with diet to reduce total cholesterol, low‐density lipoprotein (LDL) cholesterol, triglycerides, and Apo‐B, as well as to increase high‐density lipoprotein (HDL) cholesterol.
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It is also indicated to slow the progression of coronary atherosclerosis.
Mechanism of Action
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Lescol® blocks the production of cholesterol in the liver via competitive inhibition of HMG‐CoA reductase.
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This stimulates the LDL receptors, thereby increasing uptake of the LDL particle.
Pharmacokinetics and Metabolism
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The drug is rapidly absorbed following oral ingestion.
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Peak concentrations of Lescol XL® are achieved in about 3 hours under fasting conditions, and are metabolized primarily through the 2c9 pathway.
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Administration of the drug following a high‐fat meal delays its absorption.
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The drug is 98% bound to plasma proteins.
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It is metabolized in the liver via hydroxylation.
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Elimination is primarily via the feces as metabolites, with very little (<5%) excreted in the urine.
Precautions and Adverse Reactions
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Potential for drug accumulation exists in patients with hepatic insufficiency.
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Women tend to have slightly higher plasma concentrations than men.
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Liver function studies must be performed before therapy and at 12‐week intervals after drug initiation or an increase in the dose.
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The drug must be discontinued if there is a three‐fold increase above the upper limited normal in the liver function tests.
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The drug must be discontinued if myalgias develop or there is an increase in creatine phosphokinase enzymes.
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The most common adverse reactions, although rare, are diarrhea, dyspepsia, fatigue, nausea, and flatulence.
Contraindications
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Lescol XL® is contraindicated in patients with liver disease.
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It is contraindicated in patients who are pregnant or are trying to become pregnant.
Dosage and Administration
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Prior to initiation of therapy, patients should be placed on a low‐fat, low‐cholesterol diet.
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In patients whose LDL cholesterol goal reduction is >25%, the recommended starting dose is 40 or 80 mg/day.
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The dosing range is 20–80 mg/day.
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The drug can be taken in the evening, without regard to meals.
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Periodic liver function checks should be performed, as noted above.
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Dosage changes can be made no more frequently than every 4 weeks.
Summary
Lescol XL® (co‐marketed with Reliant Pharmaceuticals) is a new dosage and preparation of the previously released synthetic HMG‐CoA reductase inhibitor Lescol®. The higher dosage is encouraging in the management of elevated lipid levels and the progression of the coronary atheroclerotic process.