Ezetimibe/Simvastatin

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

[edit] MECHANISM OF ACTION

Ezetimibe/simvastatin is a combination of two hypolipidemic medications with complementary and distinct mechanisms of action:

  • Simvastatin belongs to the class of drugs called Statins. Simvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, this results in a decrease in mevalonate, a precursor of cholesterol. Therefore Simvastatin inhibits the hepatic synthesis of VLDL and increases the uptake and catabolism of LDL cholesterol by increasing the number of hepatic LDL receptors on the cell-surface
  • Ezetimibe is a hypolipidemic drug that selectively inhibits the intestinal absorption of cholesterol and related phytosterols leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood. Ezetimibe molecular target has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols.

[edit] INDICATIONS

  • Patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia as anadjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C.
  • Patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C and total-C as an adjunct to other lipidlowering treatments.

[edit] DOSAGE

  • Adult recommended start dose: 10/10 or 10/20 mg day once daily in the evening, with or without food. Dose range is 10/10 mg/day to 10/40 mg/day
  • Patients with Homozygous Familial Hypercholesterolemia: The recommended dosage is 10/40 mg in the evening

Due to the increased risk of myopathy, including rhabdomyolysis, use of the 10/80 mg dose should be restricted to patients who have been taking 10/80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. Patients unable to achieve their LDL-C goal utilizing the 10/40 mg dose should not be titrated to the 10/80 mg dose, but should be placed on alternative LDL-C-Lowering treatment that provides greater LDL-C lowering.

Dosing of Ezetimibe/simvastatin should occur either 2 hours before or 4 hours after administration of a bile acid sequestrant (e.g. Cholestyramine)

[edit] DOSAGE FORMS AND STRENGTHS

Tablets (ezetimibe mg/simvastatin mg): 10/10, 10/20, 10/40, 10/80

[edit] CONTRAINDICATIONS

[edit] WARNINGS AND PRECAUTIONS

  • Skeletal Muscle Effects: Myalgia, myopathy and, rarely, rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including Simvastatin. These risks can occur at any dose level, but are increased at the highest dose (80 mg).
    Patients with predisposing factors for myopathy (e.g., age ≥ 65 years, inadequately treated hypothyroidism, renal impairment, personal or family history of hereditary muscular disorders, alcohol abuse) and concomitant use of Fibrates, Cyclosporine, Danazol and strong CYP3A4 inhibitors should reduce the simvastatin dosage or avoid takin it. (see Interaction).
    Whilst on treatment, patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever. Creatine Kinase levels should be measured in these patients. Therapy should be discontinued if Creatine Kinase levels are markedly elevated.
  • Liver enzyme abnormalities and monitoring: As with other HMG-CoA reductase inhibitors, persistent elevations in hepatic transaminases can occur. Monitor liver enzymes prior to initiating therapy and repeat it when clinically indicated.

[edit] INTERACTIONS

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category X (US). Ezetimibe/Simvastatin may cause fetal harm, therefore, it is contraindicated in women who are or may become pregnant
  • Nursing mothers who require Ezetimibe/Simvastatin treatment should be advised not to nurse their infants.

[edit] SIDE EFFECTS

Common (incidence ≥2% and greater than placebo) adverse reactions: headache, increased ALT, myalgia, upper respiratory tract infection, and diarrhea.

[edit] RELATED LINKS

http://www.vytorin.com/

[edit] BIBLIOGRAPHY

[edit] REFERENCES

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