Atorvas

Each film coated tablet contains Atorvastatin Calcium equivalent to 20 mg or 40 mg Atorvastatin.
Atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (a statin), is a lipid regulating drug with actions on plasma lipids. Inhibition of HMG-CoA reductase leads to reduced cholesterol synthesis in the liver and lower intracellular cholesterol concentrations; this stimulates an increase in low-density-lipoprotein (LDL)-cholesterol receptors on hepatocyte membranes, thereby increasing the clearance of LDL from the circulation. HMG-CoA reductase inhibitors (statins) reduce total cholesterol, LDL-cholesterol, and very-low-density lipoprotein (VLDL)-cholesterol concentrations in plasma. They also tend to reduce triglycerides and to increase high-density lipoprotein (HDL)-cholesterol concentrations.
It is used to reduce LDL-cholesterol, apolipoprotein B, and triglycerides, and to increase HDL-cholesterol in the treatment of hyperlipidemia, including hypercholesterolemia, combined (mixed) hyperlipidemia (type IIa or IIb hyperlipoproteinemia, hypertriglyceridemia (type IV), and primary dysbetalipoproteinemia (type III). Statins can be effective as adjunct therapy in patients with homozygous familial hypercholesterolemia who have some LDL-receptor function. It is also used for cardiovascular risk reduction in patients with atherosclerotic cardiovascular disease or diabetes mellitus.

Pharmacology: Pharmacokinetics: Atorvastatin is rapidly absorbed from the gastrointestinal tract. It has low absolute bioavailability of about 12% due to presystemic clearance in the gastrointestinal mucosa and/or first pass metabolism in the liver, its primary site of action. Atorvastatin is metabolised by the cytochrome P450 isoenzyme CYP3A4 to a number of active metabolites. It is 98% bound to plasma proteins. The mean plasma elimination half-life of Atorvastatin is about 14 hours although the half-life of inhibitory activity for HMG-CoA reductase is about 20 to 30 hours due to the contribution of the active metabolites. Atorvastatin is excreted as metabolites, primarily in the bile.

Atorvastatin is used in the treatment of hyperlipidemias, including hypercholesterolemias and combined (mixed) hyperlipidemia (type IIa or IIb hyperlipoproteinemias), hypertriglyceridemia (type IV) and dysbetalipoproteinemia (type III).
It is also used as adjunctive therapy in patients with homozygous familial hypercholesterolemia. It is also used for primary prophylaxis of cardiovascular events.

The usual initial dose is 10 to 20 mg of Atorvastatin once daily; an initial dose of 40 mg daily may be used in patients who require large reduction in LDL-cholesterol. The dose may be adjusted at intervals of 4 weeks up to a maximum of 80 mg daily.
Children and adolescents aged 10 to 17 years with heterozygous familial hypercholesterolemia may be given atorvastatin in an initial dose of 10 mg once daily, adjusted according to response to a maximum of 20 mg once daily.

In case of overdosage, consult the physician immediately.

Hypersensitivity to the contents of the drug product.
Active liver disease or unexplained persistently raised serum aminotransferase concentrations.
It is contra-indicated in pregnancy, in breast feeding mothers and in women of childbearing potential.

Porphyria: Unsafe for patients with porphyria because it has been shown to be porphyrinogenic in animals
Use in Children: Potential effects of statins on growth and sexual development because patients require lifelong therapy.
Use in Pregnancy: Statins have the possibility to affect fetal sterol synthesis.

The commonest adverse effects of therapy with statins are gastrointestinal disturbances. Other adverse effects reported include headache, skin rashes, dizziness, blurred vision, insomnia, and dysgeusia. Reversible increases in serum-aminotransferase concentrations may occur and liver function should be assessed before treatment is initiated and then monitored periodically until one year after the last elevation in dose. Hepatitis and pancreatitis have been reported. Hypersensitivity reactions including anaphylaxis and angioedema have also occurred. Myopathy, characterized by myalgia and muscle weakness and associated with increased creatine phosphokinase concentrations, has been reported, especially in patients taking statins concurrently with ciclosporin, fibric acid derivatives, or nicotinic acid. Rarely rhabdomyolysis with acute renal failure may develop.

The most serious consequence of drug interactions with statins is the development of myopathy or rhabdomyolysis. Drugs that can cause myopathy when given alone increase the risk of myopathy with all statins; these drugs include fibric acid derivatives (fibrates or gemfibrozil), and nicotinic acid. The risk of myopathy is also increased by drugs that increase plasma levels of statins by inhibiting their metabolism. Since the statins have different metabolic pathways, these interactions depend on the individual drug concerned. Atorvastatin is metabolized by the cytochrome P450 isoenzyme CYP3A4 and interactions may occur with drugs that inhibit this enzyme, including ciclosporin, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV-protease inhibitors, nefazodone, amiodarone, and verapamil; there may also be similar interaction with grapefruit juice Such combinations should be used with caution, if at all. Statins may also have effects on other drugs. Bleeding and increases in prothrombin time have been reported in patients taking statins with coumarin anticoagulants.
Antibacterials: Erythromycin and other macrolides are inhibitors of the cytochrome P450 isoenzyme CYP3A4 and may increase plasma concentration and the risk of myopathy with some statins. Rifampicin has been reported to reduce plasma concentration of Atorvastatin.
Anticoagulants: Bleeding and increased prothrombin time in patients receiving oral anticoagulants with statins.
Antifungals: Itraconazole and ketoconazole may increase plasma concentrations and the risk of myopathy with some statins.
Antivirals: HIV-protease inhibitors may increase plasma concentrations of statins.
Calcium-channel blockers: Rhabdomyolysis and hepatitis have been reported in a patient receiving Atorvastatin with diltiazem.
Grapefruit juice: May increase plasma concentration of Atorvastatin.
Immunosuppressants: Reports of myopathy and rhabdomyolysis in patients receiving Atorvastatin with ciclosporin.
Lipid regulating drugs: Myopathy and myositis are adverse effects of statins and fibric acid derivatives including fibrates, gemfibrozil, also with nicotinic acid.
Proton pump inhibitors: Reduction in the first pass metabolism of Atorvastatin due to the inhibition of p-glycoprotein by esomeprazole.

Store at temperatures not exceeding 30°C. Protect from light and moisture.

Dyslipidaemic Agents

C10AA05 - atorvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.

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