Rosuvastatin

Rosuvastatin is a prescription drug used for the treatment of "high cholesterol" (hyperlipidemia and mixed dyslipidemia). Rosuvastatin belongs to a family of drugs called statins. Other members of this family include atorvastatin (Lipitor) and simvastatin (Zocor). Statins reduce cholesterol levels by inhibiting the enzyme HMG-CoA reductase. The Food and Drug Administration (FDA) approved the use of rosuvastatin in August 2003. Rosuvastatin is marketed as Crestor by AstraZeneca.

Gross pathology of atherosclerosis, aorta. This aorta has been cut open to reveal atherosclerosis in the wall of the vessel. Statins like rosuvastatin are used to reduce cholesterol levels and the risk or progression of atherosclerosis. Source: Wikimedia Commons

Uses

Rosuvastatin is used to reduce elevated total cholesterol, low-density lipoprotein (LDL, the so-called "bad cholesterol"), apolipoprotein B, non-high-density lipoprotein cholesterol, and triglycerides. Rosuvastatin is also used to increase high-density lipoprotein (HDL, so-called "good cholesterol"). The following are the problems for which Rosuvastatin is used in adults:

• Primary hyperlipidemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia (an inherited form of very high cholesterol)

Rosuvastatin is also used in adults to slow the progression of atherosclerosis and to treat hypertriglyceridemia. This disorder is characterized by high concentrations of fats (lipids) in the blood.

How Rosuvastatin is Taken

Rosuvastatin is available in 5 mg, 10 mg, 20 mg, and 40 mg oral tablets.

For hyperlipidemia, mixed dyslipidemia, hypertriglyceridemia and slowing atherosclerosis progression

For all disorders except familial hypercholesterolemia, the recommended starting dose of rosuvastatin is 10 mg once daily. For people with marked hyperlipidemia (LDL > 190 mg/dL) which requires marked reduction, a 20 mg starting dose is sometimes used. The dose may be adjusted after two weeks.

Homozygous familial hypercholesterolemia

The recommended starting dose for homozygous familial hypercholesterolemia is 20 mg once daily. The dose may be adjusted after two weeks.

How Rosuvastatin Works

Rosuvastatin inhibits HMG-CoA reductase, which is an enzyme in the liver that converts HMG-CoA to the cholesterol precursor mevalonate. This inhibition results in the decrease of cholesterol production by the body.

Inhibition of HMG-CoA and the resulting reduction in cholesterol has two consequences. First, it increases the number of LDL receptors on the surface of liver cells, which enhances uptake and breakdown of LDL particles. Second, it inhibits the liver's synthesis of very low density lipoproteins (VLDL), which reduces the total number of VLDL and LDL particles.

How the Body Affects Rosuvastatin

Peak circulating levels of rosuvastatin are reached 3–5 hours post-dosing. Rosuvastatin is not extensively metabolized. A small portion is metabolized in the liver by the CYP2C9 enzyme. The time needed for the concentration of rosuvastatin in the blood to be reduced by half (the half-life), is approximately 19 hours. Rosuvastatin is primarily excreted in the feces.

Side Effects

Below are the most common side effects of rosuvastatin (occurring in 2% of people):

• Headache
• Myalgia (muscle aches)
• Abdominal pain
• Feelings of weakness
• Nausea

Risks and Precautions

Rhabdomyolysis, a dangerous breakdown of muscle, has been reported with the use of some statins. Rosuvastatin also carries this risk. However, the U.S. Food and Drug Administration (FDA) suggests that the risk with rosuvastatin is no greater than that for other statins. Symptoms of rhabdomyolysis include muscle pain, tenderness, or weakness, particularly if accompanied by malaise (makred tiredness) or fever. The FDA has also warned about a risk of kidney damage with rosuvastatin use.

Any antacids containing aluminum and magnesium hydroxide can interact with rosuvastatin. Taking these antacids two hours after taking rosuvastatin avoids the interaction.

Drug Interactions

The following drugs have been shown to interact with rosuvastatin:

• Cyclosporine (Neoral)
• Gemfibrozil (Lopid)
• Lopinavir/Ritonavir
• Coumarin anticoagulants (e.g., warfarin)

Niacin

Cyclosporine has been shown to elevate blood levels of rosuvastatin in heart transplant recipients.^[1]Gemfibrozil increased blood levels of rosuvastatin in a study of healthy volunteers.^[2] In these interactions, the concomitant drug may be inhibiting the uptake of rosuvastatin into the liver.

Rosuvastatin has been shown to increase the blood thinning effect of warfarin in both healthy volunteers and patients under maintenance warfarin.^[3] The mechanism underlying this interaction is not known.

Alternatives

Several statins are available for cholesterol control, including atorvastatin and simvastatin. Simvastatin is also available in combination with ezetimibe (Zetia) in a formulation called Vytorin.

Controversy

Citing safety concerns, the U.S. consumer interest organization Public Citizen petitioned the FDA in 2004 to remove rosuvastatin from the market. In March of 2005 the FDA denied the request. The FDA stated that, based on data from clinical trials, rosuvastatin and other statins on the U.S. market have similar safety profiles.

Research

One study, called the STELLAR trial, compared the effectiveness of all statins in patients with high cholesterol.^[4] This trial, which was the largest of its kind to date, showed that rosuvastatin had the greatest effect on cholesterol levels. More patients in that group achieved cholesterol level goals, as outlined by American and European guidelines, compared to the number of patients achieving goals with the other statins.

References

1. ↑ Simonson SG, Raza A, Martin PD, et al. Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clin Pharmacol Ther. 2004 Aug;76(2):167-77. Abstract
2. ↑ Schneck DW, Birmingham BK, Zalikowski JA, et al. The effect of gemfibrozil on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther. 2004 May;75(5):455-63. Abstract
3. ↑ Simonson SG, Martin PD, Mitchell PD, Lasseter K, Gibson G, Schneck DW. Effect of rosuvastatin on warfarin pharmacodynamics and pharmacokinetics. J Clin Pharmacol. 2005 Aug;45(8):927-34. Abstract
4. ↑ Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003 Jul 15;92(2):152-60. Abstract

External Links

FDA: Patient Information Sheet