Potent CYP3A4 inhibitors (clarithromycin, HIV protease inhibitors, cyclosporine) Adjustments in simvastatin strength reduce potential statin-associated toxicities, including fatigue and myopathy. *Doses are adjusted to target goal LDL levels.ĭose adjustments are necessary with simvastatin when taken concomitantly with certain pharmacotherapy. For stable patients on the simvastatin 80-mg dose, a change of therapy is necessary if initiating an interacting medication. Recommendations are to use a high-intensity statin instead.
Simvastatin 80 mg is not recommended for patients with LDL targets that are not at goal, even with simvastatin 40 mg. Therefore, the 80-mg strength is restricted for only those patients who have been on the 80-mg regimen for 12 or more months with no reported myopathy. In patients with coronary heart disease (CHD), the initial dose is 40 mg once every eveningĪ dose restriction exists for simvastatin 80 mg due to a higher risk of myopathy and possible rhabdomyolysis, especially within the first 12 months of use. Studies have shown that early statin therapy initiation has reduced the incidence of cardiovascular events, leading to reduced mortality. These properties are commonly taken advantage of when prescribing statin therapy for individuals with normal cholesterol levels. These include inhibition of platelet aggregation, reduction in inflammation at the site of atherosclerotic plaque, and improved endothelial function. Statins also possess additional properties in addition to their ability to lower cholesterol concentrations. Simvastatin acts on the rate-limiting step and serves as an HMG-CoA reductase inhibitor, consequently leading to decreased cholesterol concentrations. Using acetyl-CoA as a substrate, mevalonic acid is formed, and subsequent reactions lead to the formation of cholesterol. The rate-limiting step in this pathway involves the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase enzyme. The biosynthesis of this molecule consists of a multi-step pathway. Clinicians prescribe statin therapy to lower cholesterol concentrations simvastatin targets cholesterol production.