Patients are commonly advised to stop eating grapefruits or drinking grapefruit juice while on statin therapy.
Concomitant medications administered with simvastatin should have an assessment performed for potential drug interactions to minimize the risk of adverse effects. Īdditional serious reactions include interstitial lung disease, diabetes mellitus, erythema multiforme, leukopenia, hemolytic anemia, thrombocytopenia, and Stevens-Johnson syndrome, although these adverse events are rare.ĭrug concentrations, and consequently, incidence and severity of adverse effects, can become significantly increased when coadministered with CYP3A4 inhibitors. Adverse musculoskeletal effects include greater than a three-fold increase in creatine phosphokinase (CPK) levels, rhabdomyolysis, and compartment syndrome in the lower legs.
Rarer, yet more severe, causations include cardiovascular effects such as atrial fibrillation, hepatic abnormalities, including cholestatic hepatitis, greater than a 3-fold elevation in transaminases, jaundice, and potential liver failure. Potent CYP3A4 inhibitors (clarithromycin, HIV protease inhibitors, cyclosporine)Ĭommon adverse effects include headaches, myalgia, abdominal pain, gastritis, constipation, upper respiratory infections, elevated AST or ALT, and impaired serum glucose control. 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. It is excreted in the feces and urine and has a half-life of between two and five hours. Simvastatin is hepatically metabolized via the CYP450 enzyme system, primarily through CYP3A4 as well as CYP2C6 this figures prominently in some of its potential adverse effects and drug-drug interactions, of which more later. 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.