Each film-coated tablet contains: Atorvastatin (as Calcium) 40 mg.
Pharmacology: Pharmacodynamics: Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme responsible for the conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Triglycerides and cholesterol in the liver are incorporated into very low-density lipoproteins (VLDL) and released into the plasma for delivery to peripheral tissues. Low-density lipoprotein (LDL) is formed from VLDL and is catabolized primarily through the receptor with high affinity to LDL (LDL receptor).
Atorvastatin lowers plasma cholesterol and lipoprotein serum concentrations by inhibiting HMG-CoA reductase and subsequently cholesterol biosynthesis in the liver and increases the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.
Atorvastatin reduces LDL production and the number of LDL particles. Atorvastatin produces a profound and sustained increase in LDL receptor activity coupled with a beneficial change in the quality of circulating LDL particles. Atorvastatin is effective in reducing LDL-C in patients with homozygous familial hypercholesterolemia, a population that has not usually responded to lipid-lowering medicinal products.
Atorvastatin has been shown to reduce concentrations of total-C (30% - 46%), LDL-C (41% - 61%), apolipoprotein B (34% - 50%), and triglycerides (14% - 33%) while producing variable increases in HDL-C and apolipoprotein A1 in a dose response study. These results are consistent in patients with heterozygous familial hypercholesterolemia, nonfamilial forms of hypercholesterolemia, and mixed hyperlipidemia, including patients with non-insulin dependent diabetes mellitus.
Reductions in total-C, LDL-C, and apolipoprotein B have been proven to reduce risk for cardiovascular events and cardiovascular mortality.
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 metabolized 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.
For primary hypercholesterolemia, heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia as combined (mixed) hyperlipidemia in patients who have not responded adequately to diet and other appropriate measures.
Atorvastatin is given by mouth as the calcium salt. 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 a large reduction in LDL-cholesterol. The dose may be adjusted at intervals of 4 weeks up to a maximum of 80 mg daily. Or as prescribed by the physician.
There is no specific treatment for Atorvastatin overdosage. In the event of an overdose, the patient should be treated symptomatically and supportive measures instituted as required. Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance Atorvastatin clearance.
Hypersensitivity to any component of this medication, active liver disease or unexplained persistent elevations of serum transaminases. Atorvastatin calcium is contraindicated in pregnancy, in breast feeding mothers and in women of child bearing potential not using adequate contraceptive measures.
Use in Children: Safety and efficacy have not been established.
Atorvastatin should be used with caution in patients who consumes substantial quantities of alcohol and/or have a history of liver disease. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of Atorvastatin.
Skeletal Muscle: Rhabdomyolysis with or without renal impairment has been reported with the use of HMG-CoA reductase inhibitors.
Myalgia has been reported in patients treated with Atorvastatin. Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatinine phosphokinase (CPK) values greater than 10 times the upper limit of normal, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. As with other HMG-CoA reductase inhibitors, the risk of myopathy during treatment with Atorvastatin is increased with concurrent administration of immunosuppressive drugs, including cyclosporine, fibric acid derivatives, nicotinic acid, azole antifungals or erythromycin.
Effects on ability to drive and use machines: Atorvastatin has negligible influence on the ability to drive and use machines.
Women of childbearing potential: Women of childbearing potential should use appropriate contraceptive measures during treatment.
Pregnancy: Atorvastatin is contraindicated during pregnancy. Safety in pregnant women has not been established. No controlled clinical trials with Atorvastatin have been conducted in pregnant women. Rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors have been received. Studies in animals have shown toxicity to reproduction.
Maternal treatment with Atorvastatin may reduce the foetal levels of mevalonate which is a precursor of cholesterol biosynthesis. Atherosclerosis is a chronic process, and ordinarily discontinuation of lipid-lowering medicinal products during pregnancy should have little impact on the long-term risk associated with primary hypercholesterolemia.
For these reasons, Atorvastatin should not be used in women who are pregnant, trying to become pregnant or suspect they are pregnant. Treatment with Atorvastatin should be suspended for the duration of pregnancy or until it has been determined that the woman is not pregnant.
Breastfeeding: It is unknown whether Atorvastatin or its metabolites are excreted in human milk. In rats, plasma concentrations of Atorvastatin and its active metabolites are similar to those in milk. Because of the potential for serious adverse reactions, women taking Atorvastatin should not breastfeed their infants. Atorvastatin is contraindicated during breastfeeding.
Fertility: In animal studies Atorvastatin had no effect on male or female fertility.
Diarrhoea, constipation, flatulence, dyspepsia, abdominal pain, headache, nausea, myalgia, arthralgia, asthenia, insomnia, rash, muscle cramps, myositis, myopathy, paraesthesia, peripheral neuropathy, pancreatitis, hepatitis, cholestatic jaundice, anorexia, vomiting, alopecia, pruritus, impotence, hyperglycaemia and hypoglycaemia.
HMG-CoA reductase inhibitors: Risk of myopathy.
Antacid: Decreased plasma concentrations of Atorvastatin approximately 35%.
Antipyrine: Because Atorvastatin does not affect the pharmacokinetics of Antipyrine.
Colestipol: Plasma concentrations of Atorvastatin decreased approximately 25%.
Cholestyramine: No data is available.
Cimetidine: Atorvastatin plasma concentrations and LDL-C reduction were not altered.
Digoxin: Increased steady-state plasma digoxin concentrations by approximately 20%.
Erythromycin: Plasma concentrations of Atorvastatin increased approximately 40%.
Oral contraceptives: Increased AUC values of norethindrone and ethinylestradiol approximately 30% and 20%, respectively.
Warfarin: Atorvastatin had no clinical significant effect on prothrombin time when administered to patients receiving combined Atorvastatin and warfarin therapy for two weeks. Nevertheless, patients receiving Atorvastatin should be closely monitored when Atorvastatin is combined with warfarin therapy.
Other Concomitant Therapy: In clinical studies, Atorvastatin was used concomitantly with antihypertensive agents and oestrogen replacement therapy without evidence of clinically significant adverse interactions. Interaction studies with specific agents have not been conducted.
Store at temperatures not exceeding 30°C.
C10AA05 - atorvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.
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