Atorvastatin tablets p / o 40mg, No. 30

primary hypercholesterolemia (heterozygous familial and nonfamilial hypercholesterolemia (type II according to Frederickson);

combined (mixed) hyperlipidemia (types IIa and IIb according to Frederickson);

dysbetalipoproteinemia (type III according to Frederickson) (as an addition to the diet);

familial endogenous hypertriglyceridemia (type IV according to Frederickson), resistant to diet;

homozygous familial hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological treatments;

prevention of cardiovascular diseases:

- primary prevention of cardiovascular complications in patients without clinical signs of ischemic heart disease, but with several risk factors for its development: age over 55 years, nicotine addiction, arterial hypertension, diabetes mellitus, low level of HDL-C in blood plasma, genetic predisposition, including h.on the background of dyslipidemia;

- secondary prevention of cardiovascular complications in patients with coronary artery disease in order to reduce the total mortality rate, myocardial infarction, stroke, re-hospitalization for angina pectoris and the need for revascularization.

Before starting treatment with AtorisЃ, the patient should be transferred to a lipid-lowering diet, which must be followed during drug therapy.

Inside, regardless of food intake, once (at any time of the day, but at the same time), every day.

The recommended starting dose is 10 mg daily. The dose of the drug varies from 10 mg to 80 mg once a day and is selected taking into account the initial level of LDL-C, the goal of therapy and the individual therapeutic effect.

The therapeutic effect of AtorisЃ develops after 2 weeks of taking the drug, and the maximum effect is achieved after 4 weeks. Therefore, the dose should not be changed earlier than 4 weeks after starting the drug.

In primary (heterozygous hereditary and polygenic) hypercholesterolemia (type IIa) and mixed hyperlipidemia (type IIb), treatment begins with an initial dose of 10 mg 1 time per day, which is increased after 4 weeks, depending on the patient's response. The maximum daily dose is 80 mg.

With homozygous hereditary hypercholesterolemia, the initial dose is selected individually, depending on the severity of the disease. When using a maximum daily dose of 80 mg (once), the most optimal effect was noted.

AtorisЃ is used as an adjunctive therapy to other methods of treatment (plasmapheresis) or as the main treatment if therapy with other methods is not possible.

For elderly patients, as well as with kidney disease, dose adjustment is not required.

For patients with impaired liver function, the drug is prescribed with caution due to the slowdown in its excretion from the body. In this situation, monitoring of clinical and laboratory parameters is necessary, and if significant pathological changes are detected, the dose should be reduced, or treatment should be discontinued.

hypersensitivity to any component of the drug;

active liver disease (including active chronic hepatitis, chronic alcoholic hepatitis);

liver failure;

cirrhosis of the liver of any etiology;

an increase in the activity of hepatic transaminases of unknown origin by more than 3 times compared with VGN;

skeletal muscle disease;

pregnancy and lactation, as well as use in women of reproductive age who do not use adequate methods of contraception;

age up to 18 years (efficacy and safety of use have not been established);

galactosemia (because the drug contains lactose) or glucose / galactose malabsorption syndrome, lactase deficiency.

With care: alcoholism, history of liver disease.

pharmachologic effect

Lipid-lowering agent from the statin group. According to the principle of competitive antagonism, the statin molecule binds to that part of the coenzyme A receptor where HMG-CoA reductase is attached. Another part of the statin molecule inhibits the conversion of hydroxymethylglutarate to mevalonate, an intermediate in the synthesis of the cholesterol molecule. Inhibition of the activity of HMG-CoA reductase leads to a series of sequential reactions, as a result of which the intracellular cholesterol content decreases and a compensatory increase in the activity of LDL receptors occurs and, accordingly, an acceleration of the catabolism of LDL cholesterol (Xc). The lipid-lowering effect of statins is associated with a decrease in the level of total cholesterol due to LDL cholesterol. The decrease in LDL cholesterol is dose-dependent and not linear, but exponential.The inhibitory effect of atorvastatin on HMG-CoA reductase is approximately 70% determined by the activity of its circulating metabolites. Statins do not affect the activity of lipoprotein and hepatic lipases, do not have a significant effect on the synthesis and catabolism of free fatty acids, therefore their effect on the TG level is secondary and is mediated through their main effects on lowering the level of LDL-C. A moderate decrease in the level of TG during treatment with statins, apparently, is associated with the expression of remnant (apo E) receptors on the surface of hepatocytes involved in the catabolism of DID, which comprise about 30% TG. Compared with other statins (with the exception of rosuvastatin), atorvastatin causes a more pronounced decrease in TG levels. In addition to the lipid-lowering action,statins have a positive effect on endothelial dysfunction (preclinical sign of early atherosclerosis), on the vascular wall, the state of atheroma, improve the rheological properties of blood, have antioxidant, antiproliferative properties. Atorvastatin lowers cholesterol levels in patients with homozygous familial hypercholesterolemia, which usually does not respond to lipid-lowering therapy.

Pharmacokinetics

Atorvastatin is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability is low - about 12%, which is due to presystemic clearance in the gastrointestinal mucosa and / or due to the 'first pass' through the liver, mainly at the site of action. Atorvastatin is metabolized with the participation of the isoenzyme CYP3A4 with the formation of a number of substances that are inhibitors of HMG-CoA reductase. T1 / 2 from plasma is about 14 hours, although T1 / 2 of the inhibitor of HMG-CoA reductase activity is about 20-30 hours, which is due to the participation of active metabolites. Plasma protein binding is 98%. Atorvastatin is excreted in the form of metabolites mainly in the bile.

Side effect

From the nervous system:> 1% - insomnia, dizziness; <1% - headache, asthenia, malaise, drowsiness, nightmares, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesis, migraine, depression, hypesthesia, loss of consciousness. From the senses: <1% - amblyopia, ringing in the ears, dryness of the conjunctiva, impaired accommodation, retinal hemorrhage, deafness, glaucoma, parosmia, loss of taste, taste perversion. From the side of the cardiovascular system:> 1% - chest pain; <1% - palpitations, symptoms of vasodilation, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris. From the hematopoietic system: <1% - anemia, lymphadenopathy, thrombocytopenia. From the respiratory system:> 1% - bronchitis,rhinitis; <1% - pneumonia, dyspnea, exacerbation of bronchial asthma, epistaxis. From the digestive system:> 1% - nausea; <1% - heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, liver dysfunction, rectal bleeding, melena, bleeding gums, tenesmus. From the musculoskeletal system:> 1% - arthritis; <1% - leg muscle cramps, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonia, joint contractures, joint swelling,tendopathy (sometimes with tendon rupture). From the genitourinary system:> 1% - urogenital infections, peripheral edema; <1% - dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, urgency to urinate), leukocyturia, nephritis, hematuria, vaginal bleeding, nephrourolithiasis, metrorrhagia, epididymitis, decreased libido, impotence, impaired ejaculation. Dermatological reactions:> 1% - alopecia, xeroderma, photosensitivity, increased sweating, eczema, seborrhea, ecchymosis, petechiae. From the endocrine system: <1% - gynecomastia, mastodynia. From the side of metabolism: <1% - an increase in body weight, exacerbation of gout. Allergic reactions: <1% - pruritus, skin rash, contact dermatitis, rarely - urticaria, angioedema, facial edema,anaphylaxis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome). Laboratory indicators: <1% - hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.

Application during pregnancy and lactation

Atorvastatin is contraindicated for use during pregnancy and lactation (breastfeeding). It is not known whether atorvastatin is excreted in breast milk. Given the possibility of adverse events in infants, if it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be resolved. Women of reproductive age should use adequate contraceptive methods during treatment. Atorvastatin can be used in women of reproductive age only if the likelihood of pregnancy is very low, and the patient is informed about the possible risk of treatment for the fetus.

Application for violations of liver function

Contraindication: active liver disease. Before and during treatment with atorvastatin, especially when symptoms of liver damage appear, it is necessary to monitor the indicators of liver function. With an increase in the level of transaminases, their activity should be monitored until normalization. If the activity of AST or ALT, more than 3 times higher than the norm, persists, it is recommended to reduce the dose or discontinue atorvastatin.

Application in children

In children, the experience of using atorvastatin at a dose of up to 80 mg / day is limited.

special instructions

Use with caution in patients with alcohol abuse; with indications of a history of liver disease. Before and during treatment with atorvastatin, especially when symptoms of liver damage appear, it is necessary to monitor liver function indicators. With an increase in the level of transaminases, their activity should be monitored until normalization. If the activity of AST or ALT, more than 3 times higher than the norm, persists, it is recommended to reduce the dose or discontinue atorvastatin. When symptoms of myopathy appear on the background of treatment, the activity of CPK should be determined. If a significant increase in the CPK level persists, then it is recommended to reduce the dose or cancel atorvastatin. The risk of myopathy during treatment with atorvastatin increases with the simultaneous use of cyclosporine, fibrates, erythromycin, antifungal drugs,related to azoles, and niacin. There is a likelihood of the following adverse reactions, but not in all cases there is a clear connection with the intake of atorvastatin: muscle cramps, myositis, myopathy, paresthesia, peripheral neuropathy, pancreatitis, hepatitis, cholestatic jaundice, anorexia, vomiting, alopecia, pruritus, rash, impotence, hyperglycemia and hypoglycemia. In children, the experience of using atorvastatin at a dose of up to 80 mg / day is limited. Atorvastatin is used with caution in patients with chronic alcoholism.hyperglycemia and hypoglycemia. In children, the experience of using atorvastatin at a dose of up to 80 mg / day is limited. Atorvastatin is used with caution in patients with chronic alcoholism.hyperglycemia and hypoglycemia. In children, the experience of using atorvastatin at a dose of up to 80 mg / day is limited. Atorvastatin is used with caution in patients with chronic alcoholism.

Drug interactions

With the simultaneous use of atorvastatin with digoxin, the concentration of digoxin in the blood plasma slightly increases. Diltiazem, verapamil, isradipine inhibit the isoenzyme CYP3A4, which is involved in the metabolism of atorvastatin, therefore, when used simultaneously with these calcium channel blockers, it is possible to increase the concentration of atorvastatin in the blood plasma and increase the risk of myopathy. With the simultaneous use of itraconazole, the concentration of atorvastatin in the blood plasma significantly increases, apparently due to inhibition by itraconazole of its metabolism in the liver, which occurs with the participation of the isoenzyme CYP3A4; increased risk of developing myopathy. With the simultaneous use of colestipol, it is possible to reduce the concentration of atorvastatin in the blood plasma, while the lipid-lowering effect is enhanced.With the simultaneous use of antacids containing magnesium hydroxide and aluminum hydroxide, reduce the concentration of atorvastatin by about 35%. With the simultaneous use of cyclosporine, fibrates (including gemfibrozil), antifungal drugs of azole derivatives, nicotinic acid, the risk of myopathy increases. With the simultaneous use of erythromycin, clarithromycin, the concentration of atorvastatin in plasma moderately increases, the risk of myopathy increases. With the simultaneous use of ethinyl estradiol, norethisterone (norethindrone), the concentration of ethinyl estradiol, norethisterone and (norethindrone) in the blood plasma slightly increases. With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.containing magnesium hydroxide and aluminum hydroxide, reduce the concentration of atorvastatin by about 35%. With the simultaneous use of cyclosporine, fibrates (including gemfibrozil), antifungal drugs of azole derivatives, nicotinic acid, the risk of myopathy increases. With the simultaneous use of erythromycin, clarithromycin, the concentration of atorvastatin in plasma moderately increases, the risk of myopathy increases. With the simultaneous use of ethinyl estradiol, norethisterone (norethindrone), the concentration of ethinyl estradiol, norethisterone and (norethindrone) in the blood plasma slightly increases. With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.containing magnesium hydroxide and aluminum hydroxide, reduce the concentration of atorvastatin by about 35%. With the simultaneous use of cyclosporine, fibrates (including gemfibrozil), antifungal drugs of azole derivatives, nicotinic acid, the risk of myopathy increases. With the simultaneous use of erythromycin, clarithromycin, the concentration of atorvastatin in plasma moderately increases, the risk of myopathy increases. With the simultaneous use of ethinyl estradiol, norethisterone (norethindrone), the concentration of ethinyl estradiol, norethisterone and (norethindrone) in the blood plasma slightly increases. With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.With the simultaneous use of cyclosporine, fibrates (including gemfibrozil), antifungal drugs of azole derivatives, nicotinic acid, the risk of myopathy increases. With the simultaneous use of erythromycin, clarithromycin, the concentration of atorvastatin in plasma moderately increases, the risk of myopathy increases. With the simultaneous use of ethinyl estradiol, norethisterone (norethindrone), the concentration of ethinyl estradiol, norethisterone and (norethindrone) in the blood plasma slightly increases. With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.With the simultaneous use of cyclosporine, fibrates (including gemfibrozil), antifungal drugs of azole derivatives, nicotinic acid, the risk of myopathy increases. With the simultaneous use of erythromycin, clarithromycin, the concentration of atorvastatin in plasma moderately increases, the risk of myopathy increases. With the simultaneous use of ethinyl estradiol, norethisterone (norethindrone), the concentration of ethinyl estradiol, norethisterone and (norethindrone) in the blood plasma slightly increases. With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.With the simultaneous use of erythromycin, clarithromycin, the concentration of atorvastatin in plasma moderately increases, the risk of myopathy increases. With the simultaneous use of ethinyl estradiol, norethisterone (norethindrone), the concentration of ethinyl estradiol, norethisterone and (norethindrone) in the blood plasma slightly increases. With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.With the simultaneous use of erythromycin, clarithromycin, the concentration of atorvastatin in plasma moderately increases, the risk of myopathy increases. With the simultaneous use of ethinyl estradiol, norethisterone (norethindrone), the concentration of ethinyl estradiol, norethisterone and (norethindrone) in the blood plasma slightly increases. With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.