Simvastatin (Dosage)

Simvastatin is a drug of the statin family used to lower blood cholesterol levels and thus prevent the onset of cardiovascular disease. Variants in the SLCO1B1 gene, which is responsible for transporting the drug to the liver, can help determine the optimal therapeutic dose of this drug and thus minimize its side effects.

Simvastatin is a statin drug used, in combination with diet, weight loss and exercise, to treat hypercholesterolemia and hypertriglyceridemia and to reduce mortality and the incidence of cardiovascular events in high-risk individuals.

It is also used to reduce in blood the amount of fatty substances such as LDL cholesterol (low density lipoprotein-cholesterol) and increase the amount of HDL cholesterol (high desnsity lipoprotein-cholesterol) commonly called "good cholesterol".

Simvastatin is hydrolyzed in the liver to its active form ß-hydroxy acid, which is a potent inhibitor of HMG-CoA reductase that catalyzes the conversion of HMG-CoA to mevalonate, the initial and limiting step in cholesterol biosynthesis.

CONTRAINDICATIONS

Hypersensitivity, active liver disease or persistent and unexplained elevations of serum-rich transaminases, pregnancyconcomitance with potent CYP3A4 inhibitors (itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors (nelfinavir), boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, gemfibrozil, cyclosporine or danazol.

PRECAUTIONS

Severe renal insufficiency, patients who consume large amounts of alcohol. Monitor and discontinue if serum transaminases exceed 3 times the ULN (upper limit of normal). Risk of muscle disorders (myalgia, myopathy, and rarely rhabdomyolysis), monitor if tenderness, muscle weakness or muscle cramps appear.

Warnings and precautions for patients with predisposing factors to rhabdomyolysis (R.I., hypothyroidism, previous history of muscle toxicity from a statin or a fibrate, personal or family history of hereditary muscle disease or alcoholism, elderly, women), determine CK creatine kinase values (do not initiate if CK > 5 times LSN).

Risk of developing immune-mediated necrotizing myopathy. Discontinue temporarily in case of major surgery.

Not recommended in children < 10 years (lack of information in prepubertal children and in girls before menarche).

SIDE EFFECTS

Constipation, dyspepsia, flatulence, nausea, vomiting, abdominal pain, anorexia. Insomnia, fatigue, headache, depression, memory loss, blurred vision, tinnitus, rash, alopecia, rhinosinusitis, nasopharyngitis, flu-like syndrome.

Transient elevation of transaminases and creatine kinase, myalgias, myositis, rhabdomyolysis, thrombocytopenia, chest pain, peripheral edema, hyper/hypoglycemia.

PHARMACOLOGICAL INTERACTIONS

Drug interactions associated with increased risk of myopathy/rhabdomyolysis.

Increases the effect of oral anticoagulants (determine prothrombin time before starting treatment and at the beginning of starting treatment with some frequency).

BRAND NAMES

  • Alcosin®
  • Arudel®
  • Belmalip® Belmalip® Belmalip® Belmalip® Belmalip® Belmalip® Belmalip
  • Colemin® Colemin® Colemin® Colemin® Colemin® Colemin® Colemin® Colemin®
  • Glutasey®
  • Histop®
  • Lipidien® Lipidien® Lipidien® Lipidien® Lipidien® Lipidien® Lipidien
  • Pantok® Pantok
  • Zocor®

Genes analyzed

SLCO1B1

Bibliography

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