Atorvastatin Ozone tablets p / o 10mg, No. 30

Х Primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia (type IIa according to Fredrickson's classification);

Х combined (mixed) hyperlipidemia (type IIa and IIb according to the Fredrickson classification);

Х dysbetalipoproteinemia (type III according to the Fredrickson classification) (as an addition to the hypocholesterol diet);

Х familial endogenous hypertriglyceridemia (type IV according to the Fredrickson classification), resistant to a cholesterol diet;

Х homozygous familial hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological methods of treatment;

Х primary prevention of cardiovascular complications in patients without clinical signs of coronary heart disease, but with several risk factors for its development: age over 55, nicotine addiction, arterial hypertension, diabetes mellitus, low plasma HDL-C concentration, genetic predisposition, including against the background of dyslipidemia;

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

Inside. Take at any time of the day, regardless of food intake. Before starting treatment with the drug, one should try to achieve control of hypercholesterolemia with diet, exercise and weight loss in obese patients, as well as therapy for the underlying disease. When prescribing the drug, the patient must be recommended a standard cholesterol-lowering diet, which he must adhere to during the entire period of therapy. The dose of the drug varies from 10 mg to 80 mg once a day and is titrated taking into account the initial concentration of LDL-C, the purpose of therapy and the individual effect on the therapy. The maximum daily dose of the drug for a single dose is 80 mg.At the beginning of treatment and / or during an increase in the dose of the drug, it is necessary to monitor the concentration of lipids in the blood plasma every 2-4 weeks and adjust the dose of the drug accordingly. Primary hypercholesterolemia and combined (mixed) hyperlipidemia For most patients - 10 mg 1 time per day; the therapeutic effect appears within 2 weeks of therapy and usually reaches a maximum within 4 weeks. With prolonged treatment, the effect persists. Homozygous familial hypercholesterolemia In most cases, 80 mg is prescribed once a day (decrease in the concentration of LDL-C by 18-45%). Lack of liver function If liver function is insufficient, the dose of the drug should be reduced, with regular monitoring of the activity of 'liver' transaminases: aspartate aminotransferase (AST) and alanine aminotransferase (ALT).Lack of renal function Impaired renal function does not affect the concentration of atorvastatin in the blood plasma or the degree of decrease in the concentration of LDL-C during drug therapy, therefore, dose adjustment of the drug is not required. Elderly patients Differences in the efficacy, safety or therapeutic effect of the drug in elderly patients compared with the general population were not found and dose adjustment is not required (see section 'Pharmacokinetics'). Use in combination with other drugs. If necessary, the simultaneous use with cyclosporine, the dose of the drug should not exceed 10 mg per day (see section 'Special instructions'). Care should be taken to use the lowest effective dose of atorvastatin when used concomitantly with HIV protease inhibitors, hepatitis C inhibitors, clarithromycin, and itraconazole.

1 tablet contains

Active substance: in terms of atorvastatin - 10, 20, 40 or 80 mg.

Excipients (core): lactose monohydrate (milk sugar) - 43.71 mg,

microcrystalline cellulose - 15.00 mg, sodium lauryl sulfate - 0.50 mg, povidone-K25 - 2.50 mg, calcium carbonate - 17.50 mg, sodium carboxymethyl starch - 4.00 mg, magnesium stearate - 0.95 mg.

Excipients (shell): hypromellose - 1.71 mg, macrogol-4000 - 0.45 mg, titanium dioxide - 0.84 mg.

Hypersensitivity to any component of the drug.

Active liver disease or an increase in the activity of 'hepatic' transaminases in the blood plasma of unknown origin more than 3 times compared with the upper limit of normal (UHN).

Age up to 18 years (there is not enough clinical data on the effectiveness and safety of the drug in this age group).

Use in women of reproductive age who do not use adequate methods of contraception. Pregnancy, breastfeeding period.

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Composition

1 tablet contains

Active substance: in terms of atorvastatin - 10, 20, 40 or 80 mg.

Excipients (core): lactose monohydrate (milk sugar) - 43.71 mg,

microcrystalline cellulose - 15.00 mg, sodium lauryl sulfate - 0.50 mg, povidone-K25 - 2.50 mg, calcium carbonate - 17.50 mg, sodium carboxymethyl starch - 4.00 mg, magnesium stearate - 0.95 mg.

Excipients (shell): hypromellose - 1.71 mg, macrogol-4000 - 0.45 mg, titanium dioxide - 0.84 mg.

Pharmacotherapeutic group

Lipid-lowering agent - inhibitor of GM G-CoA reductase.

pharmachologic effect

Synthetic lipid-lowering agent. Atorvastatin is a selective competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A-reductase (HMG-CoA reductase), a key enzyme that converts 3-hydroxy-3-methylglutaryl-CoA into mevalonate, a precursor of sterols, including cholesterol. In patients with homozygous and heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia, and mixed dyslipidemia, atorvastatin reduces the plasma concentration of total cholesterol (CS), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (very lipoprotein) a (very lipoprotein) a low density (VLDL-C) and triglycerides (TG), causes an unstable increase in the concentration of high-density lipoprotein cholesterol (HDL-C). Atorvastatin reduces the concentration of cholesterol and lipoproteins in the blood plasma,inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and increasing the number of 'hepatic' LDL receptors on the cell surface, which leads to increased uptake and catabolism of LDL-C. Atorvastatin reduces the formation of LDL-C and the number of LDL particles, causes a pronounced and persistent increase in the activity of LDL-receptors in combination with favorable qualitative changes in LDL-particles, and also reduces the concentration of LDL-C in patients with homozygous hereditary familial hypercholesterolemia resistant to therapy with other hypolipidemic means. Atorvastatin in doses from 10 mg to 80 mg reduces the concentration of total cholesterol by 30-46%, LDL-C - by 41-61%, Apo-B - by 34-50% and TG - by 14-33%. The results of therapy are similar in patients with heterozygous familial hypercholesterolemia,non-familial forms of hypercholesterolemia and mixed hyperlipidemia, including in patients with type 2 diabetes mellitus. In patients with isolated hypertriglyceridemia, atorvastatin reduces the concentration of total cholesterol, LDL-C, VLDL-C, Apo-B and TG and increases the concentration of HDL-C. In patients with dysbetalipoproteinemia, atorvastatin reduces the concentration of intermediate density lipoprotein cholesterol. In patients with hyperlipoproteinemia of type ?? a and ?? b according to Fredrickson, the average value of the increase in the concentration of HDL-C during treatment with atorvastatin (10-80 mg) compared with the initial indicator is 5.1-8.7% and does not depend on the dose. There is a significant dose-dependent decrease in the value of the ratios: total cholesterol / HDL-C and LDL-C / HDL-C by 29-44% and 37-55%, respectively.Atorvastatin at a dose of 80 mg significantly reduces the risk of ischemic complications and mortality rates by 16% after a 16-week course, and the risk of re-hospitalization for angina pectoris, accompanied by signs of myocardial ischemia, by 26%. In patients with different baseline concentrations of LDL-C, atorvastatin causes a reduction in the risk of ischemic complications and mortality (in patients with myocardial infarction without Q wave and unstable angina pectoris, as well as in men and women, and in patients younger and older than 65 years). The decrease in plasma concentration of LDL-C correlates better with the dose of the drug than with its concentration in the blood plasma. The dose is selected taking into account the therapeutic effect (see section 'Dosage and Administration'). The therapeutic effect is achieved 2 weeks after the start of therapy,reaches a maximum after 4 weeks and lasts throughout the entire period of therapy. Atorvastatin 10 mg reduces fatal and non-fatal outcomes of coronary heart disease (CHD) compared with placebo in hypertensive patients with three or more risk factors.

Indications for use

Х Primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia (type IIa according to Fredrickson's classification);

Х combined (mixed) hyperlipidemia (type IIa and IIb according to the Fredrickson classification);

Х dysbetalipoproteinemia (type III according to the Fredrickson classification) (as an addition to the hypocholesterol diet);

Х familial endogenous hypertriglyceridemia (type IV according to the Fredrickson classification), resistant to a cholesterol diet;

Х homozygous familial hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological methods of treatment;

Х primary prevention of cardiovascular complications in patients without clinical signs of coronary heart disease, but with several risk factors for its development: age over 55, nicotine addiction, arterial hypertension, diabetes mellitus, low plasma HDL-C concentration, genetic predisposition, including against the background of dyslipidemia;

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

Contraindications

Hypersensitivity to any component of the drug.

Active liver disease or an increase in the activity of 'hepatic' transaminases in the blood plasma of unknown origin more than 3 times compared with the upper limit of normal (UHN).

Age up to 18 years (there is not enough clinical data on the effectiveness and safety of the drug in this age group).

Use in women of reproductive age who do not use adequate methods of contraception. Pregnancy, breastfeeding period.

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Method of administration and dosage

Inside. Take at any time of the day, regardless of food intake. Before starting treatment with the drug, one should try to achieve control of hypercholesterolemia with diet, exercise and weight loss in obese patients, as well as therapy for the underlying disease. When prescribing the drug, the patient must be recommended a standard cholesterol-lowering diet, which he must adhere to during the entire period of therapy. The dose of the drug varies from 10 mg to 80 mg once a day and is titrated taking into account the initial concentration of LDL-C, the purpose of therapy and the individual effect on the therapy. The maximum daily dose of the drug for a single dose is 80 mg.At the beginning of treatment and / or during an increase in the dose of the drug, it is necessary to monitor the concentration of lipids in the blood plasma every 2-4 weeks and adjust the dose of the drug accordingly. Primary hypercholesterolemia and combined (mixed) hyperlipidemia For most patients - 10 mg 1 time per day; the therapeutic effect appears within 2 weeks of therapy and usually reaches a maximum within 4 weeks. With prolonged treatment, the effect persists. Homozygous familial hypercholesterolemia In most cases, 80 mg is prescribed once a day (decrease in the concentration of LDL-C by 18-45%). Lack of liver function If liver function is insufficient, the dose of the drug should be reduced, with regular monitoring of the activity of 'liver' transaminases: aspartate aminotransferase (AST) and alanine aminotransferase (ALT).Lack of renal function Impaired renal function does not affect the concentration of atorvastatin in the blood plasma or the degree of decrease in the concentration of LDL-C during drug therapy, therefore, dose adjustment of the drug is not required. Elderly patients Differences in the efficacy, safety or therapeutic effect of the drug in elderly patients compared with the general population were not found and dose adjustment is not required (see section 'Pharmacokinetics'). Use in combination with other drugs. If necessary, the simultaneous use with cyclosporine, the dose of the drug should not exceed 10 mg per day (see section 'Special instructions'). Care should be taken to use the lowest effective dose of atorvastatin when used concomitantly with HIV protease inhibitors, hepatitis C inhibitors, clarithromycin, and itraconazole.

Application during pregnancy and lactation

Atorvastatin is contraindicated for use during pregnancy and lactation (breastfeeding).

Side effects

From the nervous system: more often 2% - insomnia, dizziness; less often 2% - headache, asthenia, malaise, drowsiness, nightmares, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesis, migraine, depression, hypesthesia, loss of consciousness.

From the senses: less often 2% - amblyopia, ringing in the ears, dry conjunctiva, impaired accommodation, retinal hemorrhage, deafness, glaucoma, parosmia, loss of taste, taste perversion.

From the side of the cardiovascular system: more often 2% - chest pain; less often 2% - a feeling of palpitations, symptoms of vasodilation, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris.

From the hematopoietic system: less often 2% - anemia, lymphadenopathy, thrombocytopenia.

From the respiratory system: more often 2% - bronchitis, rhinitis; less often 2% - pneumonia, dyspnea, exacerbation of bronchial asthma, epistaxis.

From the digestive system: more often 2% - nausea; less often 2% - 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: more often 2% - arthritis; less often 2% - leg muscle cramps, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonia, joint contractures.

From the urinary system: more often 2% - peripheral edema; less often 2% - dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, urge to urinate, nephritis, hematuria, nephrourolithiasis.

On the part of the genitals and mammary gland: more often 2% - urogenital infections; less often 2% - vaginal bleeding, metrorrhagia, epididymitis, decreased libido, impotence, impaired ejaculation, gynecomastia, mastodynia.

Skin and subcutaneous tissue disorders: more often 2% - alopecia, xeroderma, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

Allergic reactions: less often 2% - skin itching, skin rash, contact dermatitis' rarely - urticaria, angioedema, facial edema, photosensitivity, anaphylaxis, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (syndrome Lyell).

On the part of laboratory parameters: less often 2% - hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.

Others: less often 2% - an increase in body weight, exacerbation of gout.

Overdose

Treatment: there is no specific antidote; symptomatic therapy is shown. Hemodialysis is ineffective.

Drug interactions

The risk of myopathy during treatment with other drugs of this class increases with the simultaneous use of cyclosporine, fibrates, erythromycin, antifungal agents related to azoles, and nicotinic acid.

With the simultaneous use of the drug atorvastatin inside and a suspension containing magnesium and aluminum hydroxide, the concentration of atorvastatin in the blood plasma decreased by about 35%, but the degree of decrease in the concentration of cholesterol / LDL did not change.

With the simultaneous use of atorvastatin does not affect the pharmacokinetics of antipyrine (phenazone), therefore, interaction with other drugs metabolized by the same cytochrome isoenzymes is not expected.

With the simultaneous use of colestipol, the concentration of atorvastatin in the blood plasma decreased by about 25%. However, the hypolipidemic effect of the combination of atorvastatin and colestipol was superior to that of each drug separately.

With repeated administration of digoxin and atorvastatin at a dose of 10 mg, Css of digoxin in blood plasma did not change. However, when using digoxin in combination with atorvastatin at a dose of 80 mg / day, the concentration of digoxin increased by about 20%. Patients receiving digoxin in combination with Atorvastatin should be monitored.

With the simultaneous use of atorvastatin and erythromycin (500 mg 4 times / day) or clarithromycin (500 mg 2 times / day), which inhibit cytochrome CYP3A4, an increase in the concentration of atorvastatin in the blood plasma was observed.

With the simultaneous use of atorvastatin (10 mg 1 time / day) and azithromycin (500 mg 1 time / day), the concentration of atorvastatin in the blood plasma did not change.

Atorvastatin did not have a clinically significant effect on the concentration of terfenadine in blood plasma, which is metabolized mainly by cytochrome CYP3A4; in this regard, it seems unlikely that atorvastatin is able to significantly affect the pharmacokinetic parameters of other CYP3A4 substrates.

With the simultaneous use of atorvastatin and an oral contraceptive containing norethindrone and ethinyl estradiol, there was a significant increase in the AUC of norethindrone and ethinyl estradiol by about 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving Atorvastatin.

Concomitant use with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone) increases the risk of a decrease in endogenous steroid hormones (care should be taken).

When studying the interaction of atorvastatin with warfarin and cimetidine, no signs of a clinically significant interaction were found.

With the simultaneous use of atorvastatin 80 mg and amlodipine 10 mg, the pharmacokinetics of atorvastatin in the equilibrium state did not change.

There was no clinically significant undesirable interaction of atorvastatin and antihypertensive drugs.

The simultaneous use of atorvastatin with protease inhibitors known as CYP3A4 inhibitors was accompanied by an increase in the concentration of atorvastatin in blood plasma.

Pharmaceutical incompatibility is unknown.

special instructions

Before starting therapy with Atorvastatin, the patient must be prescribed a standard hypocholesterol diet, which he must follow during the entire period of treatment. The use of inhibitors of HMG-CoA reductase to reduce the concentration of lipids in the blood can lead to changes in biochemical parameters reflecting liver function. Liver function should be monitored before starting therapy, 6 weeks, 12 weeks after starting the use of Atorvastatin and after each dose increase, as well as periodically, for example, every 6 months. An increase in the activity of liver enzymes in the blood serum can be observed during therapy with Atorvastatin. Patients who have an increase in enzyme activity should be monitored until the values ??return to normal values. In that case,if ALT or ACT values ??are more than 3 times higher than ULN, it is recommended to reduce the dose of Atorvastatin or stop treatment.

Atorvastatin should be used with caution in patients with alcohol abuse and / or liver disease. Active liver disease or a persistent increase in the activity of aminotransferases of unknown origin are contraindications to the appointment of Atorvastatin.

Treatment with Atorvastatin can cause myopathy. The diagnosis of myopathy (pain and weakness in muscles in combination with an increase in CPK activity by more than 10 times compared to VHN) should be discussed in patients with widespread myalgias, muscle soreness or weakness and / or a pronounced increase in CPK activity. Patients should be warned to inform their doctor immediately if they experience unexplained muscle pain or weakness if accompanied by malaise or fever. Therapy with Atorvastatin should be discontinued in case of a pronounced increase in CPK activity or in the presence of confirmed or suspected myopathy. The risk of myopathy in the treatment of other drugs of this class increased with the simultaneous use of cyclosporine, fibrates, erythromycin, nicotinic acid or antifungal agents from the azole group.Many of these drugs inhibit CYP3A4-mediated metabolism and / or drug transport. Atorvastatin is biotransformed by CYP3A4. Prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, antifungal agents from the azole group or nicotinic acid in lipid-lowering doses, the expected benefits and risks of treatment should be carefully weighed and patients should be monitored regularly to detect pain or weakness in the muscles, especially during the first months treatment and during periods of increasing the dose of any drug. In such situations, periodic determination of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy.Atorvastatin is biotransformed by CYP3A4. Prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, antifungal agents from the azole group or nicotinic acid in lipid-lowering doses, the expected benefits and risks of treatment should be carefully weighed and patients should be monitored regularly to detect pain or weakness in the muscles, especially during the first months treatment and during periods of increasing the dose of any drug. In such situations, periodic determination of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy.Atorvastatin is biotransformed by CYP3A4. Prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, antifungal agents from the azole group or nicotinic acid in lipid-lowering doses, the expected benefits and risks of treatment should be carefully weighed and patients should be monitored regularly to detect pain or weakness in the muscles, especially during the first months treatment and during periods of increasing the dose of any drug. In such situations, periodic determination of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy.antifungal agents from the azole group or nicotinic acid in lipid-lowering doses, the expected benefits and risks of treatment should be carefully weighed and patients should be regularly monitored for pain or muscle weakness, especially during the first months of treatment and during periods of increasing doses of any drug. In such situations, periodic determination of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy.antifungal agents from the azole group or nicotinic acid in lipid-lowering doses, the expected benefits and risks of treatment should be carefully weighed and patients should be regularly monitored for pain or muscle weakness, especially during the first months of treatment and during periods of increasing doses of any drug. In such situations, periodic determination of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy.although such control does not prevent the development of severe myopathy.although such control does not prevent the development of severe myopathy.

ѕри применении препарата јторвастатин, как и других средств этого класса, описаны случаи рабдомиолиза с острой почечной недостаточностью, обусловленной миоглобинурией. “ерапию препаратом јторвастатин следует временно прекратить или полностью отменить при по¤влении признаков возможной миопатии или наличии факторов риска развити¤ почечной недостаточности на фоне рабдомиолиза (например, т¤жела¤ остра¤ инфекци¤, артериальна¤ гипотензи¤, серьезна¤ операци¤, травма, т¤желые обменные, эндокринные и электролитные нарушени¤ и неконтролируемые судороги).

ѕеред началом терапии препаратом јторвастатин необходимо попытатьс¤ добитьс¤ контрол¤ гиперхолестеринемии путем адекватной диетотерапии, повышени¤ физической активности, снижени¤ массы тела у больных с ожирением и лечени¤ других состо¤ний.

ѕациентов необходимо предупредить о том, что им следует немедленно обратитьс¤ к врачу при по¤влении необъ¤снимых болей или слабости в мышцах, особенно если они сопровождаютс¤ недомоганием или лихорадкой.

¬ли¤ние на способность к вождению автотранспорта и управлению механизмами

ќ неблагопри¤тном вли¤нии препарата јторвастатин на способность к управлению автомобилем и работе с механизмами не сообщалось.

‘орма выпуска

“аблетки, покрытые пленочной оболочкой 10 мг, 20 мг, 40 мг и 80 мг. ѕо 10, 30 таблеток в контурную ¤чейковую упаковку из пленки поливинилхлоридной и фольги алюминиевой печатной лакированной. ѕо 10, 20, 30, 40, 50, 90 или 100 таблеток в банки полимерные или в банки из полиэтилентерефталата. ќдну банку или 1, 2, 3, 4, 9 или 10 контурных ¤чейковых упаковок вместе с инструкцией по применению помещают в картонную упаковку (пачку).

Conditions of dispensing from pharmacies

Dispensed by prescription.