Wilovast

Pharmacologic Category: Antihyperlipidaemic.
Pharmacology: Pharmacodynamics: Rosuvastatin is a lipid regulating drug with actions on plasma lipids and competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase), the rate determining enzyme for cholesterol synthesis. Inhibition of HMG CoA Reductase leads to reduced cholesterol synthesis in the liver and lower intracellular cholesterol concentrations.
This stimulates in low-density lipoprotein (LDL)-cholesterol receptors on hepatocyte membranes, thereby increasing the clearance of LDL from the circulation. HMG CoA reductase inhibitors (also called statins) reduce total cholesterol, LDL-cholesterol, and very low-density lipoprotein (VLDL)-cholesterol concentrations in the plasma.
Pharmacokinetics: Peak plasma concentrations of rosuvastatin were reached 5 hours following oral dosing. The absolute bioavailability of rosuvastatin is approximately 20%.
Rosuvastatin is 90% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations. Mean Volume of distribution at steady-state of rosuvastatin is approximately 134 liters.
Rosuvastatin is not extensively metabolized, approximately 10% of a radiolabeled dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin, which is formed principally by cytochrome P450 2C9. Overall, greater than 90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by Rosuvastatin in the parent compound.
Following oral administration, Rosuvastatin, and its metabolite are primarily excreted in feces (90%). The elimination half-life of Rosuvastatin is approximately 19 hours.

For the management of hyperlipidaemias, including primary hypercholesterolemia (type IIa), mixed dyslipidaemia (type IIb), and hypertriglyceridaemia (type IV), it may also be used in patients with homozygous familial hypercholesterolaemia.

Rosuvastatin is given by mouth in an initial dose of 5 mg to 10 mg in the evening; an initial dose of 20 mg may be used in patients with ischaemic heart disease. The dose may be adjusted at interval of not less than 4 weeks up to maximum of 80 mg once daily in three divided doses of 20 mg, 20 mg and an evening dose of 40 mg. A maximum of 10 mg once daily is recommended in those taking ciclosporine fibric acid derivatives or nicotinic acid, and the risk of myopathy must be considered. Or as prescribed by the physician.

Treatment: There is no specific treatment in the event of overdose. In case of overdose, the patient should be treated symptomatically, and supportive measures instituted as required. Liver functions and CK levels should be monitored. Hemodialysis is unlikely to be of benefit.

Rosuvastatin is contraindicated in patients with a known hypersensitivity to any component of this product.
Rosuvastatin is also contraindicated in patients with active liver disease or with unexplained persistent elevations of serum transaminases.
It is also contraindicated during pregnancy and in nursing mothers.
If the patient becomes pregnant while taking this drug, therapy should be discontinued immediately and the patient apprised of potential hazard to the fetus.

Rosuvastatin should be used with caution in patients who have a history of liver disease and/or consume substantial quantities of alcohol. Unexplained persistent transaminase elevations or active liver disease are contraindications to the use of Rosuvastatin. Rosuvastatin should be prescribed with caution in patients with predisposing factors for myopathy, such as renal impairment, advanced age, and inadequately treated hypothyroidism. As an HMG-CoA reductase inhibitor, effects of Rosuvastatin on skeletal muscle are uncomplicated myalgia, and myopathy. Patients should be advised to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Rosuvastatin therapy should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected.
The risk of myopathy during treatment with Rosuvastatin may be increased with concurrent administration of other lipid lowering therapies, cyclosporine or lopinavir/ritonavir. Rosuvastatin therapy should also be temporarily withheld in any patient with an acute serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic endocrine and electrolyte disorders or uncontrolled seizures).
Combination therapy of Rosuvastatin and Gemfibrozil should generally be avoided.

Pregnancy: Rosuvastatin is contraindicated in pregnant women.
Lactation: It is not known whether Rosuvastatin is excreted in breastmilk. Because of the potential for serious adverse reaction in breastfeed infants, use of Rosuvastatin is not recommended.

Blood Disorders: thrombocytopenia.
Hepatobiliary Disorders: hepatitis, jaundice, fatal and non-fatal hepatic failure.
Musculoskeletal Disorders: arthralgia, rare reports of immune-mediated necrotizing myopathy associated with statin use.
Nervous System Disorders: peripheral neuropathy, rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, and confusion) associated with the use of all statins. The reports are generally nonserious, and reversible upon discontinuation of treatment.
Psychiatric Disorders: depression, sleep disorders (including insomnia and nightmares).
Reproductive System and Breast Disorders: gynecomastia.
Respiratory Disorders: interstitial lung disease.
Skin and Subcutaneous Tissue Disorders: drug reaction with eosinophilia and systemic symptoms (DRESS), lichenoid drug eruption.

Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter organic anion-transporting polyprotein 1B1 (OATP1B1) and efflux transporter breast cancer resistance protein (BCRP). Concomitant administration of rosuvastatin with medical products that are inhibitors of these transporter proteins may result in increased rosuvastatin plasma concentrations and an increased risk of myopathy (see table as follows). (See table.)

Click on icon to see table/diagram/image

The simultaneous dosing of rosuvastatin with an antacid suspension containing aluminum and magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%. This effect was mitigated when rosuvastatin is administered at least 2 hours after the antacid.
Coadministration of rosuvastatin and warfarin may result in a rise in INR compared to warfarin alone. Initiate INR monitoring prior to taking rosuvastatin, cessation and dosage adjustment of rosuvastatin therapy.

Dyslipidaemic Agents

C10AA07 - rosuvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.

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