Simvastatin

What it is and how it works

Mechanism of Action Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces VLDL and TG and increases HDL-C.

Mechanism class: Hydroxymethylglutaryl-CoA Reductase Inhibitors

Indications

1. INDICATIONS AND USAGE Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with coronary heart disease (CHD) or at high risk of CHD, simvastatin tablets can be started simultaneously with diet. Simvastatin tablets are an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce the risk of total mortality by reducing CHD deaths and reduce the risk of non-fatal myocardial infarction, stroke, and the need for revascularization procedures in patients at high risk of coronary events. Reduce elevated total-C, LDL-C, Apo B, TG and increase HDL-C in patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia.

Dosage and administration (summary)

2. DOSAGE AND ADMINISTRATION Dose range is 5 to 40 mg/day. Recommended usual starting dose is 10 or 20 mg once a day in the evening. Recommended starting dose for patients at high risk of CHD is 40 mg/day. Due to the increased risk of myopathy, including rhabdomyolysis, use of the 80-mg dose of simvastatin tablets should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity.

Contraindications

4. CONTRAINDICATIONS Simvastatin tablets are contraindicated in the following conditions: Concomitant administration of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products) . Concomitant administration of gemfibrozil, cyclosporine, or danazol . Hypersensitivity to any component of this medication .

Warnings and precautions

5. WARNINGS AND PRECAUTIONS Patients should be advised of the increased risk of myopathy including rhabdomyolysis with the 80-mg dose. Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase with higher doses and concomitant use of certain medicines. Predisposing factors include advanced age (≥65), female gender, uncontrolled hypothyroidism, and renal impairment. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported.

Pregnancy

Pregnancy Pregnancy Category X Simvastatin tablets are contraindicated in women who are or may become pregnant. Lipid lowering drugs offer no benefit during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development.

Storage and supply

16. HOW SUPPLIED/STORAGE AND HANDLING Simvastatin tablets USP 5 mg are brick red coloured, round shaped, biconvex, film coated tablet debossed “SI” on one side and plain on other side.

Source: Simvastatin (Simvastatin) — US FDA prescribing information, 2019-03-25, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.