Atoris, pills 10mg, 90pcs

Composition

1 film-coated tablet,10 mg / 20 mg contains:

Core

Active ingredient:

Atorvastatin Calcium 10.36 mg / 20.72 mg, equivalent to atorvastatin 10.00 mg/20.00 mg

Auxiliary substances:

Povidone-K 25, sodium lauryl sulfate, calcium carbonate, microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, 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 version) 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, XC-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 preventionof cardiovascular complications in patients with CHD in order to reduce mortality, MI, strokes, repeated hospitalizations for angina pectoris 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.

There have been rare cases of congenital abnormalities following intrauterine exposure to HMG-CoAreductase 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.

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.

* 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).

* Concomitant use with fusidic acid.

• Antiviral therapy for hepatitis C virus (HCV) with glecaprevir/pibrentasvir.
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, because Atoris® contains lactose.

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 mellitus (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, the tendinopathy (in some cases with tendon rupture), rupture of muscles;

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 “liver” tests (ACT and ALT) in blood plasma, increased activity of serum creatine phosphokinase (CPK);

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 overall maturation and development score, Tanner stage score, and height and body weight measurement. The safety and tolerability profile in children was similar to the known safety profile of atorvastatin in adults.

The clinical safety database includes safety data for 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.

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 through diet, exercise, and weight loss in obese patients, as well as therapy for 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 necessaryto 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

The recommended starting dose is 10 mg once a day. The dose can be increased to 80 mg per day depending on the clinical effect and tolerability.

The dose of Atoris® should be selected depending on the purpose of lipid-lowering therapy. Dose adjustment should be performed at intervals of 1 time in 4 weeks or more.

Impaired liver function

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

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”).

Concomitant use 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 / day (see the section “Special instructions”).

Caution should be exercised when using the lowest effective dose of atorvastatin concomitantly with HIV protease inhibitors, hepatitis C virus protease inhibitors (boceprevir, elbasvir/grazoprevir, simeprevir), clarithromycin and itraconazole. In patients who are concomitantly using antiviral drugs for the treatment of HCV (elbasvir / grazoprevir) with atorvastatin, the dose of atorvastatin should not exceed 20 mg per day.

Overdose

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

Description

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

View at the break: white rough mass with a film shell of 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 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, interaction of with other medicines]).

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).

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 overall maturation and development score, Tanner stage score, and height and body weight measurement. The safety and tolerability profile in children was similar to the known safety profile of atorvastatin in adults.

The clinical safety database includes safety data for 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 with a Tanner score of 1 (N = 15) and ≥ 2 (N = 24) (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 decreasein LDL-C and cholesterol

Impaired renal function

Impaired renal function does not affect the concentration of atorvastatin in blood plasma or lipid metabolism, and therefore no dose adjustment is required in patients with impaired renal function.

No studies have been conducted on the use of atorvastatin in patients with end-stage renal failure. Atorvastatin is not eliminated during hemodialysis due to intensive binding to plasma proteins.

Impaired liver function

The concentration of the drug is significantly increased (With_max-approximately 16 times, AUC-approximately 11 times) in patients with alcoholic cirrhosis of the liver (Child-Pugh class B).

Hepatic uptake of all HMG inhibitors–CoAreductase, including atorvastatin, occurs with the participation of the OATP transporter%^%1%^%B%^%1. Patients with the SLCO%^%1B1 genetic polymorphism are at risk of increased exposure to atorvastatin, which may lead to an increased risk of rhabdomyolysis. Polymorphism of the gene encoding OATR%^%1%^%B%^% 1 (SLCO%^%1B1 c. 521CC) is associated with a 2.4-fold increase in atorvastatin exposure (AUC) compared to patients without such a genotypic change (p. 521TT). These patients may also have impaired hepatic uptake of atorvastatin associated with genetic disorders. Possible performance implications are unknown.

Elderly patients

Plasma concentrations of atorvastatin in patients over 65 years of age are higher (with_max-about 40%, AUC-about 30%) than in young adult patients.There were no differences in the efficacy and safety of the drug, as well as in achieving the goals of lipid-lowering therapy in elderly patients compared to the general population.

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 with atorvastatin activity of” hepatic ” transaminases ACT and ALT in blood plasma. A persistent increase in the serum activity of “hepatic” transaminases (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 an increase in the activity of ACT or ALT in blood plasma by more than 3 times compared to the upper limit of normal persists, 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 CPK activity, if there is a confirmed myopathy, or if its development is suspected. The risk of developing myopathy increases with the simultaneous use of drugs that increase the concentration of atorvastatin in blood plasma (see the sections ” Interaction with other drugs “and” Pharmacological properties. Pharmacokinetics”), such as potent inhibitors of the CYP3A4 isoenzyme or transporter proteins (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, antiviral drugs for the treatment of HCV (boceprevir, telaprevir, elbasvir/grazoprevir), erythromycin, nicotinic acid in lipid-lowering doses (more than 1 g/day), ezetimibe, azole antifungal agents, colchicine. 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/day), the doctor should carefully weigh 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 (see the section “Method of use and doses”). 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 serum CPK activity 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::

· violation of kidney 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 on 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 monitoring of CPK in the blood plasma, given that these patients are already factors predisposing to the development of rhabdomyolysis,

· situation which is expected to increase the concentration of atorvastatin in plasma, such as 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 CPK activity (more than 5 times higher than 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), therapy with Atoris® 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 / day is not sufficiently defined, and therefore the possible risk of hemorrhagic stroke in such patients should be carefully evaluated before starting therapy.

After a special analysis of a clinical trial involving 4,731 patients without CHD who had suffered a stroke or TIA within the previous 6 months, who were prescribed atorvastatin 80 mg/day, a higher incidence of hemorrhagic strokes was found in the atorvastatin 80 mg 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 / 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). Both classes can lead to increased blood 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 in a patient, atorvastatin therapy should be discontinued.

Endocrine function

When using HMG-CoA reductase inhibitors (statins), including atorvastatin, there were cases of increased HbA1c 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 overall maturation and development score, Tanner stage score, and height and body weight measurement.

Special information on excipients

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

There are no data on the effect of Atoris® 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,10 mg,20 mg.

10 tablets each in a combined polyamide/aluminum foil/PVC – aluminum foil blister (Coldforming OPA/Al/PVC-Al).

1,3,6 or 9 blisters together with the instructions for use are placed in a cardboard pack.

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

Atherosclerosis, Prevention of heart attacks and strokes