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Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; undergoes extensive first-pass metabolism in the liver. Absolute bioavailability is <5%. Peak plasma concentrations are attained at 4 hours.

Onset

A therapeutic response usually is apparent within 2 weeks; maximal response occurs within 4–6 weeks.

Simvastatin-ezetimibe fixed-combination preparation (Vytorin^®) is bioequivalent to corresponding dosages of the individual components.

Distribution

Extent

Distributed mainly to the liver. Crosses the blood-brain barrier.

Plasma Protein Binding

About 95% bound to plasma proteins.

Elimination

Metabolism

Metabolized by CYP3A4 to active metabolites.

Elimination Route

Excreted in urine (13%) and feces (60%).

Half-life

0.5–3 hours.

Special Populations

Patients with moderate to severe renal insufficiency may have decreased clearance of simvastatin and its metabolites.

Stability

Storage

Oral

Tablets

Simvastatin: 5–30°C.

Fixed-combination of simvastatin and ezetimibe (Vytorin^®): Well-closed containers at 20–25°C.

Actions

• Prodrug requiring hydrolysis in vivo for activity.
• Inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis. Reduces serum concentrations of total cholesterol, LDL-cholesterol, apo B, and triglycerides.
• Statins may slow progression and/or induce regression of atherosclerosis in coronary and/or carotid arteries, modulate BP in hypercholesterolemic patients with hypertension, and possess anti-inflammatory activity.

Advice to Patients

• Importance of informing patients about risks, especially rhabdomyolysis, associated with statins alone or combined with other drugs. Importance of patients promptly reporting muscle pain, tenderness, or weakness; brown urine; flu-like symptoms; and malaise.
• Importance of adhering to nondrug therapies and measures (i.e., therapeutic lifestyle changes, including dietary management, weight control, physical activity, and management of potentially contributory disease [e.g., diabetes mellitus]).
• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed. Necessity for clinicians to advise women and adolescent girls to avoid pregnancy (i.e., using effective and appropriate contraceptive methods) during therapy and to advise pregnant women of risk to fetus.
• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.

AHFS Drug Information. © Copyright, 1959-2008, Selected Revisions April 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.