Atorvastatin

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Atorvastatin.jpg

[edit] MECHANISM OF ACTION

Atorvastatin 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 .

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

[edit] INDICATIONS

  • Hyperlipidemia:
    • Patients with primary hypercholesterolemia and mixed dyslipidemia (elevated LDL-cholesterol and triglyceride) as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C
    • Patients with hypertriglyceridemia as an adjunct to diet
    • Patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet
    • Patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C and total-C.
    • Pediatric Patients 10 to 17 years of age with Heterozygous Familial Hypercholesterolemia (HeFH) to reduce elevated total-C, LDL-C and ApoB after failing an adequate trial of diet therapy


  • Prevention of Cardiovascular Disease: 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. Atorvastatin is indicated to slow the progression of atherosclerosis and to reduce the risk of myocardial infarction, angina, stroke and arterial revascularization procedures (e.g. heart bypass, angioplasty) in patients WITHOUT clinically evident coronary heart disease, but WITH multiple risk factors such as diabetes, high blood pressure, smoking, obesity, family history of early heart disease, low HDL-C and age.
  • Prevention of Cardiovascular Disease: In patients WITH clinically evident coronary heart disease

[edit] DOSAGE

  • Adult recommended starting dose: 10 or 20 mg once daily. Maximum: 80mg/day
  • Patients requiring large LDL-C reduction (>45%) may start at 40 mg once daily.
  • Pediatric starting dose (10-17 years of age): 10 mg once daily; maximum recommended dose: 20 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 atorvastatin, lipid levels should be analyzed within 2 to 4 weeks, and dosage adjusted accordingly.

[edit] DOSAGE FORMS AND STRENGTHS

Tablets: 10, 20, 40, and 80 mg

[edit] CONTRAINDICATIONS

  • Known hypersensitivity to Atorvastatin
  • Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels
  • Women who may become pregnant, pregnancy and breastfeeding

[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 Atorvastatin. These risks can occur at any dose level, but are increased at the highest dose.

    Atorvastatin should be prescribed with caution in 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).

    Concomitant use of cyclosporine, Fibrates, erythromycin, clarithromycin, the hepatitis C protease inhibitor telaprevir, combinations of HIV protease inhibitors, including saquinavir plus ritonavir, lopinavir plus ritonavir, tipranavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, and fosamprenavir plus ritonavir, niacin, or azole antifungal (e.g. Itraconazole, Ketoconazole), 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.
  • 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

  • Strong Inhibitors of CYP3A4: Atorvastatin is metabolized by CYPP3A4. Concomitant administration of strong inhibitors of CYP3A4 can lead to increases in plasma concentrations of atorvastatin;
  • Cyclosporine: Combination increases Atorvastatin exposure. Avoid Atorvastatin
  • Concomitant lipid-lowering therapies:
    • Fibrates:
      • Gemfibrozil: Due to an increased risk of myopathy/rhabdomyolysis. concomitant administration of Atorvastatin with gemfibrozil should be avoided
      • Other fibrates: the risk of myopathy during treatment is increased with concurrent administration of other fibrates. Atorvastatin should be administered with caution
    • Niacin The risk of skeletal muscle effects may be enhanced. A reduction in Atorvastatin dosage should be considered
  • Oral Contraceptives: Co-administration of Atorvastatin and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol. These increases should be considered when selecting an oral contraceptive for a woman taking.
  • Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with atorvastatin co-administered with colchicine, and caution should be exercised when prescribing atorvastatin with colchicine.
  • Digoxin: When multiple doses of atorvastatin and digoxin were coadministered, steady state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately.

[edit] PREGNANCY AND LACTATION

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

[edit] SIDE EFFECTS

The most commonly reported adverse reactions were: nasopharyngitis (inflammation of the nasal passages, pain in the throat), nose bleed, joint pain, muscle pain, back pain, diarrhea, and urinary tract infection

See also WARNINGS AND PRECAUTIONS section

[edit] RELATED LINKS

http://www.pfizer.com/products/rx/rx_product_lipitor.jsp

[edit] BIBLIOGRAPHY

http://labeling.pfizer.com/ShowLabeling.aspx?id=587

[edit] REFERENCES