Atoris, pills 30mg, 30pcs

Composition

1 film-coated tablet,30 mg / 60 mg / 80 mg contains:

Active ingredient:

Atorvastatin Calcium 31.08 mg / 62.16 mg/82.88 mg (equivalent to atorvastatin 30.00 mg/60.00 mg/80.00 mg)

Auxiliary substances:

Lactose monohydrate, microcrystalline cellulose, PH 102, hyprolose, croscarmellose sodium, crospovidone, Type A, polysorbate 80, sodium hydroxide, magnesium stearate

Film shell:

* Opadray IIHP 85F28751 white

* Opadray IIHP 85F28751 white:

Polyvinyl alcohol, titanium dioxide (E171), macrogol-3000, talc

Pharmacological action

hypolipidemic agent-HMG-CoA reductase inhibitor

Indications

• Hypercholesterolemia:

– as an adjunct to diet to reduce elevated total cholesterol, cholesterol-LDL, APO-b, and triglycerides in adults, adolescents and children aged 10 years or older with primary hypercholesterolaemia including family hypercholesterolemia (heterozygous variant) or combined (mixed) hyperlipidemia (type IIa and IIb of the Fredrickson classification) when response to diet and other non-drug treatments are not enough;

– to reduce elevated total cholesterol, cholesterol-LDL in adults with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e. g., LDL-apheresis) or if such treatments are unavailable.

• Prevention of cardiovascular diseases:

– prevention of cardiovascular events in adult patients at high risk of developing primary cardiovascular events, as an adjunct to the correction of other risk factors;

– secondary prevention of cardiovascular complications in patients with CHD in order to reduce mortality, myocardial infarction, strokes, repeated hospitalizations for angina and the need for revascularization.

Use during pregnancy and lactation

Atoris® is contraindicated during pregnancy.

Women of reproductive age should use adequate methods of contraception during treatment. The use of Atoris® is contraindicated in women of childbearing age who do not use adequate methods of contraception.

Rare cases of congenital abnormalities have been reported after intrauterine exposure to HMG-CoA reductase inhibitors (statins). Toxic effects on reproductive function have been shown in animal studies. Atoris® is contraindicated during breast-feeding. It is not known whether atorvastatin is excreted in breast milk. If it is necessary to prescribe the drug during lactation, breastfeeding should be discontinued in order to avoid the risk of adverse events in infants.

Contraindications

• Hypersensitivity to any component of the drug.
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.
• Active liver disease or an increase in the activity of” hepatic ” transaminases in blood plasma of unknown origin by more than 3 times compared to the upper limit of normal.
• Simultaneous use with fusidic acid.
• Use of antiviral agents intended for the treatment of viral hepatitis C, glecaprevir/pibrentasvir.
• Pregnancy.
• Breast-feeding period.
• Women of childbearing age who do not use adequate methods of contraception.
• Age up to 18 years (insufficient clinical data on the efficacy and safety of the drug in this age group), with the exception of heterozygous familial hypercholesterolemia (use is contraindicated in children under 10 years of age).

Side effects

Atoris® is usually well-tolerated, and adverse reactions are usually mild and transient.

Classification of the incidence of side effects recommended by the World Health Organization (WHO):

very common ≥ 1/10

common ≥ 1/100 to < 1/10

uncommon ≥ 1/1000 to < 1/100

rare ≥ 1/10000 to < 1/1000

very rare < 1/10000

frequency unknown cannot be estimated based on available data.

Infectious and parasitic diseases:

common: nasopharyngitis.

Disorders of the blood and lymphatic system:

rare: thrombocytopenia.

Immune system disorders:

common: allergic reactions;

very rare: anaphylaxis.

Metabolic and nutritional disorders:

common: hyperglycemia;

rare: hypoglycemia, weight gain, anorexia;

frequency unknown: diabetes – the frequency depends on the presence or absence of risk factors (concentration of fasting blood glucose ≥ 5.6 mmol/l, body mass index [BMI] > 30 kg/m 2 of the body surface area, increased concentration of triglycerides in plasma, arterial hypertension in anamnesis).

Mental disorders:

infrequently: “nightmarish” dreams, insomnia;

frequency unknown: depression.

Nervous system disorders:

common: headache;

infrequent: dizziness, paresthesia, hypesthesia, impaired taste perception, amnesia;

rare: peripheral neuropathy;

frequency unknown: memory loss or loss.

Visual disturbances:

infrequently: the appearance of a “veil” in front of the eyes;

rarely: visual impairment.

Hearing disorders and labyrinth disorders:

infrequently: tinnitus;

very rarely: hearing loss.

Respiratory, thoracic and mediastinal disorders:

common: sore throat, nosebleeds;

frequency unknown: isolated cases of interstitial lung disease (usually with prolonged use).

Disorders of the digestive system:

common: constipation, flatulence, dyspepsia, nausea, diarrhea;

uncommon: vomiting, abdominal pain, belching, pancreatitis, abdominal discomfort.

Liver and biliary tract disorders:

infrequently: hepatitis;

rarely: cholestasis.

Skin and subcutaneous tissue disorders:

Infrequently: urticaria, pruritus, skin rash, alopecia;

rarely: angioedema, bullous rash, polymorphic exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Musculoskeletal and connective tissue disorders:

common: myalgia, arthralgia, pain in extremities, muscle cramps, swelling, back pain, musculoskeletal pain;

infrequent: neck pain, muscle weakness;

rare: myopathy, myositis, rhabdomyolysis, muscle rupture, the tendinopathy (in some cases with tendon rupture);

very rare: volchanochnopodobny syndrome;

frequency unknown: immune-mediated necrotizing myopathy.

Kidney and urinary tract disorders:

very rare: secondary renal failure.

Genital and breast disorders:

infrequently: impotence;

very rarely: gynecomastia.

General disorders and disorders at the injection site:

infrequently: malaise, asthenic syndrome, chest pain, peripheral edema, fatigue, fever.

Laboratory and instrumental data:

often: abnormal results of plasma ACT and ALT values, increased serum creatine phosphokinase (CPK) activity;

infrequently: leukocyturia;

frequency unknown: increased concentration of glycosylated hemoglobin (HbAl).

Children

Children aged 10 to 17 years treated with atorvastatin had an adverse event profile similar to that of patients treated with placebo, with infections being the most common adverse event in both groups, regardless of the causal relationship assessment. In a 3-year study, there was no clinically significant effect on growth and puberty (according to the general maturation and development assessment, Tanner scale assessment of puberty stages, and height and body weight measurement). The safety and tolerability profile of atorvastatin in children was similar to the known profile of atorvastatin in adults.

The clinical safety database includes data from 520 children treated with atorvastatin, of whom 7 were aged Based on the available data, the frequency, type and severity of adverse reactions in children are similar to those in adults.

Interaction

During treatment with HMG-CoA reductase inhibitors with concomitant use of cyclosporine, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day) or inhibitors of the CYP3A4 isoenzyme (for example, erythromycin, clarithromycin, antifungal agents-azole derivatives) increases the risk of developing myopathy (see the section “Special instructions”).

Inhibitors of the CYP3A4 isoenzyme

Since atorvastatin is metabolized by the CYP3A4 isoenzyme, concomitant use of atorvastatin with inhibitors of the CYP3A4 isoenzyme may lead to an increase in the concentration of atorvastatin in blood plasma. The degree of interaction and potentiation effect is determined by the variability of exposure to the CYP3A4 isoenzyme.

It was found that potent inhibitors of the CYP3A4 isoenzyme lead to a significant increase in the concentration of atorvastatin in blood plasma. Should, whenever possible, avoid concurrent use of potent inhibitors of CYP3A4 (such ascyclosporine, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, Itraconazole, Posaconazole, some antiviral drugsused in the treatment of viral hepatitis C (e. g., elbassir/natprevar) and HIV protease inhibitorsincluding ritonavir, lopinavir, atazanavir, indinavir, darunavir, etc. ). If concomitant use of these drugs is necessary, consider the possibility of initiating therapy with the lowest dose and should also evaluate the possibility of reducing the maximum dose of atorvastatin.

Moderate inhibitors of the CYP3A4 isoenzyme (for example, erythromycin, diltiazem, verapamil and fluconazole) can lead to an increase in the concentration of atorvastatin in blood plasma. Concomitant use of HMG-CoA reductase inhibitors (statins) and erythromycin was associated with an increased risk of myopathy. Interaction studies of amiodarone or verapamil with atorvastatin have not been conducted. Both amiodarone and verapamil are known to inhibit the activity of the CYP3A4 isoenzyme, and concomitant use of these drugs with atorvastatin may lead to increased exposure to atorvastatin. In this regard, it is recommended to reduce the maximum dose of atorvastatin and conduct appropriate monitoring of the patient’s condition when used simultaneously with moderate inhibitors of the CYP3A4 isoenzyme. Monitoring should be carried out after the start of therapy and against the background of changing the dose of an inhibitor of the CYP3A4 isoenzyme.

Inhibitors of the OATP transport protein 1 In 1

Atorvastatin is metabolized by Cytochrome P4503A4 (CYP3A4) and is a substrate of” hepatic ” transport proteins of organic anion-transport polypeptides (OATP1B1 and OATP1B3). Atorvastatin metabolites are substrates of OATP1B1. Atorvastatin is also identified as a substrate of MDR1, a drug multiresistance transport protein 1, and BCRP protein, which may limit intestinal absorption and hepatic clearance of atorvastatin(see section ” Pharmacological properties. Pharmacokinetics“).

OATP 1 – in-1 inhibitors (e. g., cyclosporine) may increase the bioavailability of atorvastatin. Thus, the simultaneous use of atorvastatin at a dose of 10 mg and cyclosporine at a dose of 5.2 mg / kg / day leads to an increase in the concentration of atorvastatin in blood plasma by 7.7 times (see the section “Method of use and doses”). The effect of inhibition of hepatic uptake transporters on the concentration of atorvastatin in hepatocytes is unknown. If it is impossible to avoid the simultaneous use of such drugs, it is recommended to reduce the dose and monitor the effectiveness of therapy.

Gemfibrozil / fibrates

Against the background of the use of fibrates in monotherapy, undesirable reactions related to the musculoskeletal system, including rhabdomyolysis, were periodically noted. The risk of such reactions increases with the simultaneous use of fibrates and atorvastatin. If it is impossible to avoid the simultaneous use of these drugs, then the minimum effective dose of atorvastatin should be used, and regular monitoring of the patient’s condition should be carried out.

Ezetimibe

The use of ezetimibe is associated with the development of adverse reactions from the musculoskeletal system, including the development of rhabdomyolysis. The risk of such reactions increases with the simultaneous use of ezetimibe and atorvastatin. Careful monitoring is recommended for these patients.

Erythromycin/Clarithromycin

When atorvastatin and erythromycin (500 mg 4 times a day) or clarithromycin (500 mg 2 times a day), inhibitors of the CYP3A4 isoenzyme, an increase in the concentration of atorvastatin in blood plasma was observed (see the section “Special instructions”).

Protease inhibitors

Concomitant use of atorvastatin with protease inhibitors, known as CYP3A4 inhibitors, is associated with an increase in the concentration of atorvastatin in blood plasma.

Diltiazem

Concomitant use of atorvastatin at a dose of 40 mg with diltiazem at a dose of 240 mg leads to an increase in the concentration of atorvastatin in blood plasma.

Cimetidine

There was no clinically significant interaction between atorvastatin and cimetidine.

Itraconazole

Concomitant use of atorvastatin in doses from 20 mg to 40 mg and itraconazole in a dose of 200 mg led to an increase in the AUC of atorvastatin.

Grapefruit juice

Since grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme, its excessive consumption (more than 1.2 liters per day) can cause an increase in the concentration of atorvastatin in blood plasma.

Transport protein inhibitors

Atorvastatin is a substrate of liver enzyme transporters, OATP1B1 and OATP1B3 transporters. Atorvastatin metabolites are OATP1B1 substrates. Atorvastatin is also identified as a substrate of the MDR-1 and BCRP efflux transporters, which may limit intestinal absorption and biliary clearance of atorvastatin (see section ” Pharmacological properties. Pharmacokinetics“).

Concomitant use of atorvastatin at a dose of 10 mg and cyclosporine at a dose of 5.2 mg / kg / day resulted in an increase in the level of systemic exposure to atorvastatin (an increase in AUC by 8.7 times) (see the section ” Pharmacological properties. Pharmacokinetics“). Cyclosporine is an inhibitor of the 1-In-1 organic anion transport polypeptide (OATP 1-In-1),1-In-3 (OATP 1-In-1), a protein associated with MDR-1 and BCRP, as well as the CYP3A4 isoenzyme, therefore, it increases the level of systemic exposure to atorvastatin. The daily dose of atorvastatin should not exceed 10 mg (see section “Dosage and use”).

Glecaprevir and pibrentasvir are inhibitors of OATP1 In 1, OATP1 IN 1, MDR-1 and BCRP, therefore, they increase the level of exposure to atorvastatin. The daily dose of atorvastatin should not exceed 10 mg (see section “Dosage and use”).

Elbasvir and grazoprevir are inhibitors of OATR 1 In 1, OATR 1 IN 1, MDR 1 and BCRP, therefore, they increase the level of systemic exposure to atorvastatin. Atoris® should be used with caution and at the lowest required dose (see section “Dosage and use”).

Inducers of the CYP3A4 isoenzyme

Concomitant use of atorvastatin with inducers of the CYP3A4 isoenzyme (for example, efavirenz, rifampicin, or St. John’s wort) may lead to a decrease in the concentration of atorvastatin in blood plasma. Due to the dual mechanism of interaction with rifampicin (an inducer of the CYP3A4 isoenzyme and an inhibitor of the hepatocyte transport protein OATP 1 In 1), simultaneous use of atorvastatin and rifampicin is recommended, since delayed use of atorvastatin after taking rifampicin leads to a significant decrease in the concentration of atorvastatin in blood plasma. However, the effect of rifampicin on the concentration of atorvastatin in hepatocytes is unknown, and if simultaneous use cannot be avoided, the effectiveness of such a combination should be carefully monitored during therapy.

Antacids

Concomitant oral use of a suspension containing magnesium hydroxide or aluminum hydroxide reduced the concentration of atorvastatin in the blood plasma by about 35%, but the degree of reduction in the concentration of LDL-C in the blood plasma did not change.

Phenazone

Atorvastatin does not affect the pharmacokinetics of phenazone, so interaction with other drugs metabolized by the same cytochrome isoenzymes is not expected.

Kolestipol

With the simultaneous use of colestipol, the concentration of atorvastatin in blood plasma decreased by about 25%, but the lipid-lowering effect of the combination of atorvastatin and colestipol exceeded that of each drug separately.

Digoxin

When digoxin and atorvastatin were re-administered at a dose of 10 mg, the steady-state plasma concentrations of digoxin did not change. However, when digoxin was used in combination with atorvastatin at a dose of 80 mg/day, the digoxin concentration increased by about 20%. Patients receiving digoxin concomitantly with atorvastatin should be monitored accordingly.

Azithromycin

Concomitant use of atorvastatin at a dose of 10 mg once a day and azithromycin at a dose of 500 mg once a day did not change the concentration of atorvastatin in blood plasma.

Oral contraceptive medications

When atorvastatin was co-administered with oral contraceptives containing norethisterone and ethinylestradiol, there was a significant increase in the AUC of norethisterone and ethinylestradiol by approximately 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for women taking atorvastatin.

Terfenadine

There were no clinically significant changes in the pharmacokinetics of terfenadine when atorvastatin and terfenadine were co-administered.

Warfarin

In a clinical study in patients receiving regular warfarin therapy, concomitant use of atorvastatin at a dose of 80 mg per day resulted in a slight increase in prothrombin time, approximately 1.7 seconds during the first 4 days of therapy. The index returned to normal within 15 days of atorvastatin therapy. Although only rarely significant interactions affecting anticoagulant function have been reported, prothrombin time should be determined prior to initiation of atorvastatin therapy in patients receiving coumarin anticoagulants and regularly during therapy to prevent significant changes. Once the prothrombin time indicator stabilizes, it can be monitored in the same way as recommended for patients receiving coumarin anticoagulants. When changing the dose of atorvastatin or stopping therapy, prothrombin time should be monitored according to the same principles as described above. Atorvastatin therapy was not associated with the development of bleeding or changes in prothrombin time in patients who did not receive anticoagulant treatment.

Colchicine

Despite the fact that studies on the simultaneous use of colchicine and atorvastatin have not been conducted, there are reports of the development of myopathy with the use of this combination. Caution should be exercised when atorvastatin and colchicine are co-administered.

Amlodipine

Concomitant use of atorvastatin 80 mg and amlodipine 10 mg did not alter the pharmacokinetics of atorvastatin at steady state.

Fusidic acid

Post-marketing studies have reported cases of rhabdomyolysis in patients taking concomitant statins, including atorvastatin and fusidic acid. The mechanism of this interaction is unknown. In patients for whom the use of fusidic acid is considered necessary, statin treatment should be discontinued during the entire period of fusidic acid use. Statin therapy can be resumed 7 days after the last fusidic acid dose. In exceptional cases where long-term systemic therapy with fusidic acid is necessary(for example, for the treatment of severe infections), the need for simultaneous use of atorvastatin and fusidic acid should be considered on a case-by-case basis and carried out under strict medical supervision. The patient should be warned to seek immediate medical attention if symptoms such as muscle weakness, sensitivity, or pain occur.

Other concomitant therapy

In clinical trials, atorvastatin was used simultaneously with antihypertensive agents and estrogens as part of hormone replacement therapy. There were no signs of clinically significant adverse interactions, and no interaction studies with specific drugs were conducted.

In addition, there was an increase in the concentration of atorvastatin when used concomitantly with HIV protease inhibitors (combinationsof lopinavir and ritonavir, saquinavir and ritonavir, darunavir and ritonavir, fosamprenavir, as well as combinations of fosamprenavira with ritonavir and nelfinavirom), viral hepatitis C protease inhibitors (boceprevir), clarithromycin and itraconazole. Caution should be exercised when concomitantly using these drugs, as well as using the lowest effective dose of atorvastatin.

How to take, course of use and dosage

Inside. Take at any time of the day, regardless of the meal time.

Before starting treatment with Atoris®, an attempt should be made to control hypercholesterolemia and reduce body weight in obese patients through diet, exercise, and adequate treatment of the underlying disease.

When prescribing the drug, the patient should be recommended a standard hypocholesterolemic diet, which he should adhere to throughout the entire period of therapy.

The dose of Atoris® varies from 10 mg to 80 mg once a day and is selected taking into account the concentration of LDL-C in blood plasma, the purpose of therapy and the individual response to therapy.

The maximum daily dose of Atoris® is 80 mg.

At the beginning of treatment and/or during an increase in the dose of Atoris®, it is necessary to monitor the concentration of plasma lipids every 2-4 weeks and adjust the dose accordingly.

Primary hypercholesterolemia and combined (mixed) hyperlipidemia

For most patients, the recommended dose of Atoris® is 10 mg once a day, the therapeutic effect is manifested within 2 weeks and usually reaches a maximum after 4 weeks. With long-term treatment, the effect persists.

Homozygous familial hypercholesterolemia

In most cases,80 mg is prescribed once a day (a decrease in the concentration of LDL-C in blood plasma by 18-45%).

Heterozygous familial hypercholesterolemia

The initial dose is 10 mg per day. The dose should be selected individually and the relevance of the dose should be evaluated every 4 weeks with a possible increase to 40 mg per day. Then either the dose can be increased to a maximum of 80 mg per day, or it is possible to combine bile acid sequestrants with atorvastatin at a dose of 40 mg per day.

Prevention of cardiovascular diseases

In primary prevention studies, the dose of atorvastatin was 10 mg per day. It may be necessary to increase the dose in order to achieve LDL-C values that meet current recommendations.

Use in children from 10 to 18 years of age with heterozygous familial hypercholesterolemia

For patients with heterozygous familial hypercholesterolemia aged 10 years and older, the recommended starting dose of atorvastatin is 10 mg per day. The dose can be increased to 80 mg per day depending on the response and tolerability. The dose should be selected individually in accordance with the recommended therapy. Correction can be performed at intervals of 4 weeks or more. Recommendations for titrating the dose to 80 mg per day are based on data obtained in studies involving adult patients and limited data from clinical studies involving children with heterozygous familial hypercholesterolemia.

There are limited data on safety and efficacy in children with heterozygous familial hypercholesterolemia aged 6 to 10 years, obtained in open-label studies. Atoris® is contraindicated for the treatment of patients under 10 years of age. Currently available data are described in the section “Side effects”, there are no recommendations for dosage in this age category of patients.

Impaired liver function

If liver function is impaired, the dose of Atoris® should be reduced with regular monitoring of the activity of “hepatic” transaminase-aspartate aminotransferase (ACT) and alanine aminotransferase (ALT) in the blood serum.

Impaired renal function

Impaired renal function does not affect the concentration of atorvastatin or the degree of decrease in the concentration of LDL-C in blood plasma, so no dose adjustment is required.

Elderly patients

There were no differences in the therapeutic efficacy and safety of Atoris® in elderly patients compared to the general population, and no dose adjustment is required (see the section “Pharmacological properties. Pharmacokinetics“).

Use in combination with other medicinal products

If concomitant use with cyclosporine, telaprevir or a combination of tipranavir/ritonavir is necessary, the dose of Atoris® should not exceed 10 mg per day (see the sections ” Pharmacological properties. Pharmacokinetics“, “Interaction with other medicinal products”, “Special instructions”).

Caution should be exercised when using the lowest effective dose of atorvastatin concomitantly with human immunodeficiency virus(HIV) protease inhibitors, hepatitis C virus protease inhibitors (boceprevir), clarithromycin and itraconazole.

In patients taking antiviral agents intended for the treatment of viral hepatitis C, simultaneously with atorvastatin, the dose of atorvastatin should not exceed 20 mg / day (see the sections “Interaction with other drugs” and “Special instructions”).

Overdose

There is no specific antidote for the treatment of overdose with Atoris®. In case of overdose, if necessary, symptomatic treatment should be carried out. Liver function tests should be performed and serum creatinine clearance should be monitored. Since atorvastatin actively binds to plasma proteins, hemodialysis is ineffective.

Description

of the 30 mg tablet:

Round, slightly biconvex tablets, film-coated in white or almost white color, with a chamfer.

tablets 60 mg:

Oval, biconvex tablets, covered with a film-coated white or almost white color.

tablets 80 mg:

Capsule-shaped, biconvex tablets, covered with a film-coated white or almost white color.

Special instructions

In patients with risk factors for rhabdomyolysis (renal impairment, hypothyroidism, hereditary muscle disorders in the patient’s history or family history, previous toxic effects of HMG-CoA reductase inhibitors [statins] or fibrates on muscle tissue, a history of liver disease and/or use in patients who drink significant amounts of alcohol, age over 70 years, situations in which an increase in the concentration of atorvastatin in blood plasma is expected [for example, interactions with other drugs]).

It is contraindicated in persons under 18 years of age (there are insufficient clinical data on the effectiveness and safety of the drug in this age group), with the exception of heterozygous familial hypercholesterolemia (use is contraindicated in children under 10 years of age).

Use in children from 10 to 18 years of age with heterozygous familial hypercholesterolemia

For patients with heterozygous familial hypercholesterolemia aged 10 years and older, the recommended starting dose of atorvastatin is 10 mg per day. The dose can be increased to 80 mg per day depending on the response and tolerability. The dose should be selected individually in accordance with the recommended therapy. Correction can be performed at intervals of 4 weeks or more. Recommendations for titrating the dose to 80 mg per day are based on data obtained in studies involving adult patients and limited data from clinical studies involving children with heterozygous familial hypercholesterolemia.

Children aged 10 to 17 years treated with atorvastatin had an adverse event profile similar to that of patients treated with placebo, with infections being the most common adverse event in both groups, regardless of the causal relationship assessment. In a 3-year study, there was no clinically significant effect on growth and puberty (according to the general maturation and development assessment, Tanner scale assessment of puberty stages, and height and body weight measurement). The safety and tolerability profile of atorvastatin in children was similar to the known profile of atorvastatin in adults.

The clinical safety database includes data from 520 children treated with atorvastatin, of whom 7 were aged Based on the available data, the frequency, type and severity of adverse reactions in children are similar to those in adults.

In an 8-week open-label study, children (aged 6-17 years) with heterozygous familial hypercholesterolemia and an initial LDL-C concentration of ≥ 4 mmol/L were treated with atorvastatin in the form of chewable tablets of 5 mg or 10 mg or film-coated tablets at a dose of 10 mg or 20 mg 1 time per day, respectively. The only significant covariate in the pharmacokinetic model of the atorvastatin-treated population was body weight. The apparent clearance of atorvastatin in children did not differ from that in adult patients when measured allometrically by body weight. In the range of action of atorvastatin and o-hydroxyatorvastatin, there was a consistent decrease in LDL-C and cholesterol.

Impaired liver function

If liver function is impaired, the dose of Atoris® should be reduced with regular monitoring of the activity of “hepatic” transaminase-aspartate aminotransferase (ACT) and alanine aminotransferase (ALT) in the blood serum.

Impaired renal function

Impaired renal function does not affect the concentration of atorvastatin or the degree of decrease in the concentration of LDL-C in blood plasma, so no dose adjustment is required.

Elderly patients

There were no differences in the therapeutic efficacy and safety of Atoris® in elderly patients compared to the general population, and no dose adjustment is required.

Effects on the liver

As with other lipid-lowering agents of this class, a moderate increase (more than 3 times higher than the upper limit of normal)was observed during treatment with atorvastatinindicators of ACT and ALT in blood plasma. A persistent increase (more than 3 times higher than the upper limit of normal) was observed in 0.7% of patients treated with atorvastatin. The frequency of such changes when using atorvastatin at doses of 10 mg,20 mg,40 mg and 80 mg was 0.2%,0.2%,0.6% and 2.3%, respectively. Increased activity of “hepatic” transaminases in blood plasma was usually not accompanied by jaundice or other clinical manifestations. With a reduction in the dose of atorvastatin, temporary or complete withdrawal of the drug, the activity of” hepatic ” transaminases in blood plasma returned to the initial level. Most patients continued to take atorvastatin at a reduced dose without any clinical consequences.

Before starting therapy,6 weeks and 12 weeks after starting Atoris®, or after increasing its dose, liver function indicators should be monitored. Liver function should also be monitored when there are clinical signs of liver damage. If the activity of “hepatic” transaminases in the blood plasma increases, the activity of ALT and ACT in the blood plasma should be monitored until it normalizes. If the increase in the activity of ACT or ALT in blood plasma persists by more than 3 times compared to the upper limit of normal, it is recommended to reduce the dose or cancel the drug Atoris® (see the section “Side effects”).

Atoris® should be used with caution in patients who consume significant amounts of alcohol and/or have a history of liver disease. Active liver disease or permanently increased activity of” hepatic ” plasma transaminases of unknown origin is a contraindication to the use of Atoris® (see the section “Contraindications”).

Effect on skeletal muscles

Myalgia has been reported in patients treated with atorvastatin (see section “Side effects”). The diagnosis of myopathy should be assumed in patients with diffuse myalgia, muscle soreness or weakness, and / or a marked increase in serum CPK activity (more than 10 times the upper limit of normal). Therapy with Atoris® should be discontinued if there is a marked increase in serum creatinine clearance, if there is confirmed myopathy, or if its development is suspected. The risk of myopathy during treatment with this class of drugs was increased with concomitant use of powerful inhibitors of the CYP3A4 isoenzyme (for example, cyclosporine, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole) and HIV protease inhibitors, including ritonavir, lopinavir, atazanavir, indinavir, darunavir, tipranavir/ritonavir, etc. ), gemfibrozil or other fibrates, boceprevir, erythromycin, nicotinic acid in lipid-lowering doses (more than 1 g per day), ezetimibe, azole antifungal agents, colchicine, antiviral agents used to treat viral hepatitis C (telaprevir, boceprevir or elbasvir/grazoprevir). Many of these drugs inhibit CYP3A4-mediated metabolism and / or drug transport. It is known that the CYP3A4 isoenzyme is the main liver isoenzyme involved in the biotransformation of atorvastatin. When using Atoris® in combination with fibrates, erythromycin, immunosuppressants, azole antifungal agents or nicotinic acid in lipid-lowering doses (more than 1 g per day), the doctor should carefully assess the ratio of the expected benefit of treatment and the possible risk. Patients should be regularly monitored for muscle pain or weakness, especially during the first months of therapy and during the period of increasing the dose of any of these drugs. If combination therapy is necessary, the possibility of using lower initial and maintenance doses of the above drugs should be considered. Concomitant use of atorvastatin and fusidic acid is not recommended, so temporary discontinuation of atorvastatin is recommended during fusidic acid treatment. In such situations, periodic monitoring of the CPK index can be recommended, although such monitoring does not prevent the development of severe myopathy (see the section “Interaction with other drugs”).

Before starting treatment

Atorvastatin should be used with caution in patients with factors predisposing to the development of rhabdomyolysis. Before starting atorvastatin therapy, CPK activity in blood plasma should be monitored in the following cases::

• the impairment of renal function;
• hypothyroidism;
• hereditary muscular disorders in the patient’s medical history or family history;
• already transferred the toxic effect of inhibitors of HMG-COA reductase inhibitor (statin) or fibrates in muscle tissue;
• diseases of the liver disease and/or patients who consume alcohol in large quantities;
• in patients older than 70 years should assess the need for control increased CPK in the serum, given that these patients, as a rule, there are factors predisposing to the development of rhabdomyolysis;
• situations in which an increase in the concentration of atorvastatin in blood plasma is expected, such as interactions with other drugs (see the section “Interactions with other drugs”).

In such situations, the risk/benefit ratio should be evaluated and the patient’s condition should be monitored medically.

If there is a significant increase in serum creatinine clearance (more than 5 times the upper limit of normal), atorvastatin therapy should not be initiated.

Rare cases of rhabdomyolysis with acute renal failure due to myoglobinuria have been reported with the use of Atoris®, as well as other HMG-CoA reductase inhibitors. Previous renal impairment may be a risk factor for rhabdomyolysis. Such patients should be provided with more careful monitoring of the musculoskeletal system. If there are symptoms of myopathy or risk factors for developing renal failure associated with rhabdomyolysis (for example, severe acute infection, hypotension, extensive surgery, trauma, metabolic, endocrine and water-electrolyte disorders, uncontrolled seizures), Atoris® therapy should be temporarily discontinued or completely discontinued.

Very rare cases of immune-mediated necrotizing myopathy have been reported during therapy or when statins are discontinued. Immuno-mediated necrotizing myopathy is clinically characterized by persistent weakness of the proximal muscles and increased serum CPK activity, which persist despite discontinuation of statin treatment.

Attention! Patients should be warned to seek immediate medical attention if they experience unexplained pain or muscle weakness, especially if they are accompanied by malaise or fever.

Prevention of stroke by actively reducing the concentration of cholesterol in blood plasma (SPARCL)

In a retrospective analysis of stroke subtypes, patients without CHD who had recently had a stroke or TIA and were initially treated with atorvastatin at a dose of 80 mg had a higher incidence of hemorrhagic stroke compared to patients receiving placebo. The increased risk was particularly noticeable in patients with a history of hemorrhagic stroke or lacunar infarction at the start of the study. In this group of patients, the benefit/risk ratio for taking atorvastatin at a dose of 80 mg is not well defined, and therefore the possible risk of hemorrhagic stroke in such patients should be carefully evaluated before starting therapy.

After a special analysis of the results of a clinical study involving 4,731 patients without CHD who had suffered a stroke or TIA within the previous 6 months, who were prescribed atorvastatin 80 mg per day, a higher incidence of hemorrhagic strokes was found in the atorvastatin group compared to the placebo group (55 in the atorvastatin group versus 33 in the placebo group). Patients with hemorrhagic stroke at the time of admission to the study had a higher risk for recurrent hemorrhagic stroke (7 in the atorvastatin group, versus 2 in the placebo group). However, patients treated with atorvastatin 80 mg per day had fewer strokes of any type (265 vs. 311) and fewer cardiovascular events (123 vs. 204).

Diabetes mellitus

Some evidence supports the use of HMG-CoA reductase inhibitors (statins). As a class, they can lead to an increase in plasma glucose concentrations, and individual patients at high risk of developing diabetes may develop a hyperglycemic condition that requires correction, as in diabetes mellitus. However, this risk does not exceed the benefit of treatment with HMG-CoA reductase inhibitors (statins) in terms of vascular risks, so this may not be a reason to discontinue therapy. Patients at risk (fasting blood glucose concentration of 5.6 to 6.9 mmol / L, BMI > 30 kg / m2 of body surface area, elevated TG concentration in blood plasma, arterial hypertension) should be under medical supervision, including monitoring of blood biochemical parameters, in accordance with National Recommendations.

Interstitial lung disease

Isolated cases of interstitial lung disease have been reported during treatment with certain HMG-CoA reductase inhibitors (statins), especially during long-term therapy. There may be shortness of breath, an unproductive cough, and poor overall health (fatigue, weight loss, and fever). If interstitial lung disease is suspected, atorvastatin therapy should be discontinued.

Endocrine function

When using HMG-CoA reductase inhibitors (statins), including atorvastatin, there were cases of increased HbA1 and fasting blood glucose concentrations. However, the risk of hyperglycemia is lower than the reduction in the risk of vascular complications when taking HMG-CoA reductase inhibitors (statins).

Use in children

In a 3-year study, there was no clinically significant effect on growth and puberty (according to the general maturation and development assessment, Tanner scale assessment of puberty stages, and height and body weight measurement).

Specialinformationon excipients

Atoris ® contains lactose, so its use is contraindicated in the following conditions: lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

There are no data on the effect of atorvastatin on the ability to drive vehicles and engage in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. However, given the possibility of developing dizziness, care should be taken when performing these activities.

Form of production

Film-coated tablets,30 mg,60 mg,80 mg.

10 tablets in a blister of combined OPA/Al material/PVC-aluminum foil (OPA/Al/PVC-aluminiumfoil).

3,6 or 9 blisters are placed in a cardboard pack together with the instructions for use.

Storage conditions

At a temperature not exceeding 25 ° C, in the original packaging.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use the drug after the expiration date.

Active ingredient

Atorvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Prevention of heart attacks and strokes, Atherosclerosis