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Atorvastatin is a hypocholesterolemic drug. Atorvastatin selectively and competitively inhibits HMG-CoA reductase, an enzyme that regulates the conversion rate of HMG-CoA into mevalonate, which is a precursor of sterols, including cholesterol. In patients with heterozygous and homozygous familial hypercholesterolemia, as well as non-hereditary hypercholesterolemia and mixed dyslipidemia, low cholesterol-lipoproteins, total cholesterol and apolipoprotein B are lower when taking atorvastatin. In addition, atorvastatin reduces the level of very low-density lipoproteins and triglycerides. The use of atorvastatin promotes a certain increase in the level of high-density lipoproteins. The decrease in cholesterol and lipoprotein levels in plasma under the influence of atorvastatin occurs due to a decrease in the activity of HMG-CoA reductase and a decrease in the synthesis of cholesterol in the liver, as well as an increase in the number of LDL receptors on the surface of liver cells, which contributes to an increase in the capture and catabolism of LDL. Atorvastatin intake reduces the risk of ischemia and mortality in patients of all age categories with myocardial infarction without Q wave and unstable angina. In addition, atorvastatin reduces the risk of fatal cardiovascular diseases, reduces the overall incidence of cardiovascular diseases, as well as the incidence of fatal and non-fatal stroke. After oral administration, atorvastatin is rapidly absorbed in the digestive tract and reaches peak plasma concentrations within 1-2 hours. Plasma concentrations of atorvastatin are proportional to the dose taken. The absolute bioavailability of atorvastatin with oral administration is low and reaches 12%, which is due to the presystemic clearance of atorvastatin in the mucosa of the digestive tract, as well as the effect of “first passage through the liver.” About 98% of the dose is associated with plasma proteins, atorvastatin is metabolized in the liver with the formation of pharmacologically active metabolites (the in vitro activity of ortho- and para hydroxylated compounds was similar to that of unchanged atorvastatin) and inactive substances. Atorvastatin weakly inhibits cytochrome P450 3A4. Atorvastatin and its metabolites are excreted mainly by the liver. Atorvastatin is practically not characterized by intestinal hepatic recirculation. The half-life of atorvastatin is about 14 hours, but the inhibitory activity against HMG-CoA reductase persists for 20-30 hours after a single administration of atorvastatin. The kidneys excreted less than 2% of the dose of atorvastatin taken. There is no significant difference in the pharmacokinetics of atorvastatin in people of different sex and age (excluding children with no pharmacokinetics of atorvastatin), as well as in patients with normal and reduced renal function. Atorvastatin is not excreted in hemodialysis. In patients with impaired liver function, there is a significant increase in plasma concentrations of unchanged atorvastatin. In animal studies, there was no evidence of a carcinogenic effect of atorvastatin.
Indications for use
Atorvastatin is used in complex therapy (combined with diet and exercise) in patients with elevated levels of total cholesterol, apolipoprotein B, triglycerides and low-density cholesterol-lipoproteins. Atorvastatin is prescribed for the purpose of increasing high-density cholesterol lipoproteins in patients with primary hypercholesterolemia (heterozygous familial hypercholesterolemia and non-hepatic hypercholesterolemia), combined hyperlipidemia (Fredrickson type IIa and IIb), elevated triglycerides in blood plasma (Fredrickson type IV), and patients with dysbetalipoproteinemia (Fredrickson type III) in case the diet does not give the desired effect. Atorvastatin is used to lower total cholesterol and low-density cholesterol-lipoproteins in patients with homozygous familial hypercholesterolemia (if the diet does not produce the desired effect). Atorvastatin may be administered to patients who do not have symptoms of cardiovascular disease (with or without dyslipidemia), but there are several risk factors for the development of cardiovascular diseases (including hypertension, diabetes, smoking, low cholesterol levels -lipoproteins of high density or the presence in family history of diseases of the cardiovascular system at a young age). In such patients, the administration of Atorvastatin is indicated to reduce the risk of non-fatal myocardial infarction and fatal manifestations of coronary heart disease, as well as reducing the risk of stroke, angina and the need for procedures for revascularization of the myocardium. In pediatric practice, Atorvastatin is used to treat children aged 10 to 17 years with an increased level of total cholesterol, apolipoprotein B, low-density cholesterol-lipoproteins with heterozygous familial hypercholesterolemia. The administration of atorvastatin is advisable in case of diet inefficiency (if the level of LDL-C is kept above 190 mg / dL). Also, the appointment of atorvastatin is necessary if the diet is not effective enough and there are additional risk factors (if the LDL-C level is kept above 160 mg / dL and in the family history there is an indication of cardiovascular disease at a young age or the child has several cardiovascular risk factors, including diabetes mellitus, hypertension, smoking.
Mode of application
Atorvastatin is intended for oral use. Before starting therapy with atorvastatin, the level of hypercholesterolemia should be studied with appropriate diet, exercise and other measures aimed at reducing body weight in obese patients. In addition, other diseases should also be treated prior to taking atorvastatin. Atorvastatin should be taken against a background of a standard anti-cholesterol diet. The daily dose of the drug, as a rule, is taken for 1 time, regardless of food intake. Doses of the drug Atorvastatin and the duration of therapy is determined by the doctor, given the patient’s condition, the level of hypercholesterolemia and the tolerability of atorvastatin. With primary hypercholesterolemia and mixed hyperlipidemia, as a rule, appoint atorvastatin at an initial dose of 10 mg per day. After 2-4 weeks after the start of therapy, taking into account the dynamics of the disease, the dose of atorvastatin is corrected. When homozygous familial hypercholesterolemia is usually prescribed, 40-80 mg of atorvastatin per day (taking 80 mg per day can reduce the level of low-density lipoprotein cholesterol by 18-45%). In heterozygous hypercholesterolemia, children from 10 to 17 years are usually prescribed atorvastatin at an initial dose of 10 mg per day. If necessary, after 2-4 weeks after the start of therapy, the dose is increased to 20 mg of atorvastatin per day. Older patients and patients with impaired renal function are not required to adjust the dose of atorvastatin. The maximum recommended daily intake for adults is 80 mg of atorvastatin. In pediatric practice, atorvastatin should not be used at a dose of more than 20 mg per day.
When taking the drug Atorvastatin in patients, it is possible to develop such undesirable reactions: From the side of the nervous system: insomnia, peripheral neuropathy, paresthesia, headache, asthenia. On the part of the musculoskeletal system: myopathy, myositis, convulsions, muscle pain. On the part of the digestive tract and metabolism: decreased appetite, vomiting, nausea, stools, flatulence, pancreatitis, epigastric pain, dyspepsia, changes in plasma glucose levels. From the hepatobiliary system: jaundice, cholestasis, hepatitis. Allergic reactions: urticaria, alopecia, itchy skin. Others: erectile dysfunction. With the use of the drug Atorvastatin in pediatric practice (in the treatment of children from 10 to 17 years), the development of such undesirable effects has been noted: From the side of hematopoiesis systems: thrombocytopenia. From the metabolism and digestive tract: weight gain, pain in the epigastric region, nausea. From the nervous system: memory disorders, dizziness, hypoesthesia, dysgeusia, ringing in the ears, increased fatigue. Allergic reactions: urticaria, skin itch, toxic epidermal necrolysis, erythema multiforme, bullous rash, anaphylactic shock, Quincke’s edema. Others: flu-like condition, trauma, tendon rupture, joint pain, rhabdomyolysis, peripheral edema, chest pain. It should be borne in mind that regardless of the age category of patients with the use of the drug Atorvastatin may develop myopathy, including weakness and pain in the muscles, which are accompanied by an increase in the level of creatine phosphokinase (10 and more times higher than normal). At the development of a myopathy, it is necessary to cancel a preparation Atorvastatin. The risk of this effect is increased in patients receiving cyclosporine, erythromycin, fibrotic acid derivatives, azole antifungal agents, and niacin.
Atorvastatin is not prescribed to patients with known hypersensitivity to the active component of the drug. Atorvastatin tablets should not be given to patients with lactose intolerance (in particular, patients with lactase deficiency, galactosemia, or glucose-galactose malabsorption syndrome). Atorvastatin should not be administered to patients with a severe liver disease, but also with a persistent increase in hepatic transaminase activity (3-fold higher than normal). In pediatric practice, the drug Atorvastatin is used only for the treatment of children older than 10 years. Caution should be exercised when prescribing Atorvastatin to patients with chronic alcoholism, liver disease, acute severe infections, severe electrolyte, metabolic or endocrine disorders, and also to patients who have undergone severe surgical interventions or trauma. With caution, atorvastatin should be prescribed to patients without cardiovascular disease who had a stroke or transient ischemic attack 6 months before the start of therapy with atorvastatin (atorvastatin may then increase the risk of hemorrhagic stroke, but taking atorvastatin reduces the total number of strokes and cases of development of cardiovascular diseases). It is recommended to avoid activities that require a high concentration of attention and speed of psychomotor reactions, during therapy with atorvastatin. who had a stroke or transient ischemic attack for atorvastatin 6 months before the start of therapy (atorvastatin may then increase the risk of hemorrhagic stroke, but taking atorvastatin reduces the total number of strokes and cases of cardiovascular disease). It is recommended to avoid activities that require a high concentration of attention and speed of psychomotor reactions, during therapy with atorvastatin. who had a stroke or transient ischemic attack for atorvastatin 6 months before the start of therapy (atorvastatin may then increase the risk of hemorrhagic stroke, but taking atorvastatin reduces the total number of strokes and cases of cardiovascular disease). It is recommended to avoid activities that require a high concentration of attention and speed of psychomotor reactions, during therapy with atorvastatin.
Atorvastatin should not be given to women during pregnancy, as well as to women with a high probability of pregnancy (in particular, women of reproductive age who do not use reliable contraceptive methods). In the lactation period, atorvastatin should be taken only after the end of breastfeeding. Interaction with other drugs: There is an increased risk of myopathy with combined use of atorvastatin with cyclosporine, erythromycin, fibroid acid and its derivatives, antifungal agents of the azole group, and also niacin. It is possible to reduce the flammable concentrations of atorvastatin by 25-35% when combined with colestipol and antacids containing magnesium or aluminum hydroxide, but this effect has no clinical significance. The drug Atorvastatin somewhat inhibits the activity of cytochrome P450 3A4, but the interaction of atorvastatin with drugs that are metabolized with the participation of cytochrome P450 3A4, including antipyrine, tolbutamide, terfenadine, oral contraceptives and triazolam, has no clinical significance. Possible increase in plasma concentrations of digoxin when combined with high doses of atorvastatin (80 mg of atorvastatin per day). If necessary, the combined use of the drug Atorvastatin with digoxin should monitor the plasma concentrations of the latter. With the combined use of the drug Atorvastatin with erythromycin or clarithromycin, an increase in plasma concentrations of atorvastatin is possible. Possible changes in the pharmacokinetics of oral contraceptives containing Ethinyl estradiol and norethindrone, when combined with atorvastatin. Drugs inhibiting cytochrome P450 3A4 when combined use increase the plasma concentrations of unchanged atorvastatin. In addition, a similar effect can be observed with simultaneous administration of atorvastatin and the use of grapefruit juice (especially more than 1.2 litres of grapefruit juice per day).
When taking high doses of Atorvastatin in patients, it is possible to develop rhabdomyolysis and liver function disorders. There is no specific antidote. When taking high doses of atorvastatin, it is recommended to wash the stomach and take enterosorbent funds. If necessary, perform a symptomatic treatment. Conducting hemodialysis with an overdose of atorvastatin is ineffective.
Atorvastatin should be stored and transported in its original packaging at a temperature range of 15 to 30 degrees Celsius. Subject to the storage recommendations, the drug Atorvastatin is suitable for 2 years after release.
1 coated tablet of the drug Atorvastatin 80 contains: Calcium salt of atorvastatin (in terms of atorvastatin) – 80 mg