Simvastatin

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Simvastatin belong to a group of medicines called ‘HMG-CoA reductase inhibitors’ or Statins. These medicines inhibit the production of cholesterol in the liver and lower the cholesterol and fat content in the blood.

Cholesterol is vital to the normal functioning of the body, but if the levels of cholesterol in the bloodstream are too high it can be deposited on the walls of the blood vessels. There it builds up to form plaque, which can eventually block the blood vessel.

Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Simvastatin.jpg

[edit] MECHANISM OF ACTION

Simvastatin is a hypolipidemic belonging to the class of drugs called Statins.

Cholesterol is made mainly in the liver. Statins work by blocking a key liver enzyme involved in this process, thereby slowing down the production of cholesterol in the liver. This encourages the liver to take extra cholesterol, LDL cholesterol in particular, out of the bloodstream, by increasing the number of hepatic LDL receptors on the cell-surface and thus, causing the LDL cholesterol level to decrease .

Simvastatin 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. Simvastatin reduces total-cholesterol, LDL-cholesterol, VLDL-cholesterol and TG and increases HDL-cholesterol (good cholesterol).

[edit] INDICATIONS

  • Hyperlipidemia in:
    • Patients with primary hypercholesterolemia and mixed dyslipidemia (elevated LDL-cholesterol and triglyceride) as anadjunct to diet
    • Patients with hypertriglyceridemia as an adjunct to diet
    • Patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet. Dysbetalipoproteinemia is a rare lipid disorder characterized by high levels of blood cholesterol and triglycerides
    • Patients with homozygous familial hypercholesterolemia (HoFH).
    • Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH) after failing an adequate trial of diet therapy (FDA)


  • Reductions in Risk of coronary heart disease mortality and cardiovascular Events: Cholesterol can cause coronary heart disease by narrowing the coronary arteries. This condition, called atherosclerosis, may lead to angina, a heart attack (myocardial infarction), or a stroke. Simvastatin is indicated to slow the progression of atherosclerosis and to reduce the risk of myocardial infarction, stroke and arterial revascularization procedures (e.g. heart bypass, angioplasty) in patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease.

[edit] DOSAGE

  • Adult recommended starting dose: 10 or 20 mg once daily in the evening. Dose range is 5 to 40 mg/day
  • Recommended starting dose for patients at high risk of coronary heart disease is 40 mg/day.
  • Patients with Homozygous Familial Hypercholesterolemia: The recommended dosage is 40 mg/day in the evening
  • Pediatric starting dose (10-17 years of age): 10 mg once daily; maximum recommended dose: 40 mg once daily.

Starting and maintenance dosage should be individualized according to baseline LDL-C levels, the goal of therapy, and patient response. After initiation and/or upon titration of Simvastatin, lipid levels should be analyzed after 4 weeks, and dosage adjusted accordingly.

[edit] DOSAGE FORMS AND STRENGTHS

Tablets: 5, 10, 20, 40, and 80 mg

[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).
    Simvastatin should be prescribed with caution in patients with predisposing factors for myopathy (e.g., age ≥ 65 years, female gender, inadequately treated hypothyroidism, renal impairment, personal or family history of hereditary muscular disorders, alcohol abuse).
    Concomitant use of Fibrates, niacin, verapamil, diltiazem, dronedarone, Amiodarone, amlodipine, ranolazine, Lomitapide, Grapefruit juice and strong CYP3A4 inhibitors) may increase the risk of myopathy. (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.
  • Patients should be advised of the increased risk of myopathy including rhabdomyolysis with the 80-mg dose
  • 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

Drug Interactions Associated with Increased Risk of 
Myopathy/Rhabdomyolysis
Interacting Agents 
Prescribing Recommendations 
Strong CYP3A4 inhibitors (e.g. Itraconazole, Ketoconazole, Posaconazole, Voriconazole, Erythromycin, Clarithromycin, Telithromycin, HIV protease inhibitors, Boceprevir, Telaprevir, Nefazodone)
Contraindicated with simvastatin (combination increases Simvastatin exposure)
Gemfibrozil, Cyclosporine, Danazol
Contraindicated with simvastatin (because of an increased risk of myopathy and rhabdomyolysis) 

Amiodarone, Amlodipine, Ranolazine
Do not exceed 20 mg simvastatin 
daily
Lomitapide
For patients with homozygous

familial hypercholesterolemia, do not

exceed 20 mg simvastatin daily*
Do not exceed 10 mg simvastatin 
daily 

Grapefruit juice
Avoid grapefruit juice 

* For patients with HoFH who have been taking 80 mg simvastatin chronically (e.g., for 12 months or more) without evidence of muscle toxicity, do not exceed 40 mg simvastatin when taking lomitapide.

  • Concomitant lipid-lowering therapies: Use with Fibrates or Niacin (≥1 g/day) may increase the risk of skeletal muscle effects
  • Coumarin anticoagulants (Warfarin and Acenocoumarol): Combination prolongs the International Normalised Ratio (INR). Appropriate monitoring of INR is desirable.

[edit] PREGNANCY AND LACTATION

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

[edit] SIDE EFFECTS

Most common adverse reactions (incidence ≥5.0%) are: upper respiratory infection, headache, abdominal pain, constipation, and nausea.

See also WARNINGS AND PRECAUTIONS section

[edit] RELATED LINKS

http://www.simvastatininfocenter.com/

[edit] BIBLIOGRAPHY

Zocor prescribing information U.S. (revised 10/2013)

[edit] REFERENCES