Rosuvastatin Uses and Side effects

Rosuvastatin is a lipid regulating drug, belongs to statins. Rosuvastatin is a selective, competitive inhibitor of HMG-COA reductase, an enzyme involved in the synthesis of cholesterol in the liver. Rosuvastatin is used in the treatment of primary hypercholesterolaemia, mixed dyslipidaemias or homozygous familial
hypercholesterolaemia in patients who have not responded adequately to diet and other appropriate measures.
Statins are more effective than other classes in lowering the LDL-cholesterol, they reduce coronary events, all cardiovascular events, and total mortality.

Rosuvastatin is a selective and competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-COA) reductase. This enzyme catalyzes the conversion of HMG-COA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis. Rosuvastatin produces its lipid-modifying effects in two ways. First, it increases the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL. Second, rosuvastatin inhibits hepatic synthesis of VLDL, which reduces the total number of VLDL and LDL particles. In the bloodstream, cholesterol and triglycerides (TG) circulate as part of lipoprotein Complexes.

With ultracentrifugation, these complexes separate into very-low-density lipoprotein(VLDL), intermediate-density lipoprotein (IDL), and ow-density lipoprotein (LDL) fractions that contain apolipoprotein B-100 (ApoB-100) and high-density lipoprotein (HDL) fractions. Cholesterol and TG synthesized in the liver are incorporated into VLDL and secreted into the circulation for delivery to peripheral tissues. TG are removed by the action of lipases, and in a series of steps, the modified VLDL is transformed first into IDL and then into cholesterol-rich LDL. IDL and LDL are removed from the circulation mainly by high affinity APOB/E receptors, which are expressed to the greatest extent on liver cells. HDL İs hypothesized to participate in the reverse transport of cholesterol from tissues back to the liver.

In clinical pharmacology studies in man, peak plasma concentrations of rosuvastatin were reached 3 to 5 hours following oral dosing. Both peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in approximate proportion to rosuvastatin dose. The absolute bioavailability of rosuvastatin is approximately 20%.

Administration of rosuvastatin with food does not affect the AUC. Plasma concentrations of rosuvastatin do not differ following evening or morning drug administration. Significant LDL-C reductions are seen when rosuvastatin is given with or without food, and regardless of the time of day of drug administration, Distribution: Mean volume of distribution at steady-state of rosuvastatin is approximately 134 liters, Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations.

Rosuvastatin is not extensively metabolized: approximately 10% of a radiolabeled dose is recovered as metabolite. The major metabolite is N-dimethyl rosuvastatin. which is formed principally by cytochrome P450 2C9, and in vitro studies have demonstrated that N-dimethyl rosuvastatin has approximately one sixth to one-half the HMG-CoA reductase inhibitory activity of rosuvastatin. Overall, greater than 90% of active plasma HMG-COA reductase inhibitory activity is accounted for by rosuvastatin.

Following oral administration, rosuvastatin and its metabolites are:
Primarily excreted in the feces (90%). The elimination half-life (11/2) of rosuvastatin is approximately 19 hours.

Lowering LDL Cholesterol: Rosuvastatin is effective in reducing low-density lipoprotein (LDL) cholesterol levels, commonly known as “bad” cholesterol. High levels of LDL cholesterol can lead to atherosclerosis and increase the risk of heart disease.

Raising HDL Cholesterol: It helps to increase high-density lipoprotein (HDL) cholesterol, often referred to as “good” cholesterol. Higher levels of HDL cholesterol are associated with a lower risk of cardiovascular disease.

Reducing Triglycerides: Rosuvastatin can lower triglycerides, which are a type of fat found in the blood. High levels of triglycerides can also contribute to the risk of heart disease.

Preventing Cardiovascular Events: By managing cholesterol levels and reducing the risk of atherosclerosis, rosuvastatin helps prevent cardiovascular events such as heart attacks and strokes.

Treatment of Hyperlipidemia and Hypercholesterolemia: It is commonly prescribed for patients with hyperlipidemia (high levels of lipids in the blood) and hypercholesterolemia (high cholesterol levels), including those with familial hypercholesterolemia, a genetic condition.

Slowing Progression of Atherosclerosis: By lowering cholesterol levels, rosuvastatin can slow the progression of atherosclerosis, which is the buildup of plaque in the arteries.

Primary and Secondary Prevention of Cardiovascular Disease: Rosuvastatin is used for both primary prevention (in individuals without a history of cardiovascular events but at high risk) and secondary prevention (in individuals with a history of cardiovascular events).

Rosuvastatin is generally well tolerated. Adverse reactions have
usually been mild and transient. The most frequent adverse events thought to be related to
rosuvastatin were:

• myalgia
• constipation
• asthenia
• abdominal pain
• nausea.

DRUG INTERACTIONS:

• Cytochrome P450 3A4: In vitro and in vivo data indicate that rosuvastatin clearance is not dependent on metabolism by cytochrome P450 3A4 to a clinically significant extent.
• Ketoconazole: Coadministration of ketoconazole (200 mg twice daily for 7 days) with rosuvastatin (80 mg) resulted in no change in plasma concentrations of rosuvastatin.
• Erythromycin: The Coadministration of erythromycin (500 mg four times daily for 7 days) with rosuvastatin (80 mg) decreased AUC and Cmax of rosuvastatin by 20% and 31%, respectively. Itraconazole: Itraconazole(200 mg once daily for 5 days) resulted in a 39% and 28% increase in AUC of rosuvastatin after 10 mg and 80 mg dosing, respectively. Fluconazole: Coadministration of fluconazole (200 mg once daily for 11 days) with rosuvastatin (80 mg) resulted in a 14% increase in AUC of rosuvastatin.
• Cyclosporine: administration of cyclosporine with rosuvastatin resulted in no significant changes in cyclosporine plasma concentrations However, Cmax and AUC of rosuvastatin increased 11- and 7-fold, respectively.
• Warfarin: The Coadministration of warfarin (25 mg) with rosuvastatin (40 mg) did not change warfarin plasma concentrations but increased the International Normalized Ratio (INR).
• Digoxin: so Coadministration of digoxin (0.5 mg) with rosuvastatin (40 mg) resulted in no change to digoxin plasma concentrations. Fenofibrate: Coadministration of fenofibrate (67 mg three times daily) with rosuvastatin (10 ma) resulted in no significant changes in plasma concentrations of rosuvastatin or fenofibrate.
• Gemfibrozil: As Coadministration of gemfibrozil (600 mg twice daily for 7 days) with rosuvastatin (80 mg) resulted in a 90% and 120% increase for AUC and Cmax of rosuvastatin, respectively.
• Antacid: Coadministration of an antacid (aluminum and magnesium hydroxide combination) with rosuvastatin (40 ma) resulted in a decrease in plasma concentrations of rosuvastatin by 54%. However, when the antacid was given 2 hours after rosuvastatin, there were no clinically significant changes in plasma concentrations of rosuvastatin.

Liver Enzymes: HMG-CoA reductase inhibitors, like some other lipid-lowering therapies,
have been associated I with biochemical abnormalities of liver function. It is recommended that liver
function tests should be performed before and at 12 weeks following both the initiation of therapy
and any elevation of dose, and periodically (e.g., semiannually) ) thereafter. Myopathy/Rhabdomyolysis: Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with rosuvastatin and with other drugs in this class. Pediatric Use: The safety and effectiveness in pediatric patients have not been established. Geriatric Use: The overall frequency of adverse events and types of adverse events were similar in patients above and below 65 years of age.

Overdosage: There is no specific treatment in the event of overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Hemodialysis does not significantly enhance clearance of rosuvastatin.

Store in a cool, dry and dark place between 15-30 C. Keep all medicines out of the children’s reach.

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