Atoris, 30 mg 30 pieces

Interaction

During treatment with HMG-CoA reductase inhibitors, concomitant use of cyclosporin, fibrates, nicotinic acid in lipid-lowering doses (>1 g/day) or inhibitors of CYP3A4 isoenzyme (e.g., erythromycin, clarithromycin, antifungal agents – azole derivatives) increases the risk of myopathy (see section “Special Precautions. Separate instructions).

Inhibitors of CYP3A4 isoenzyme

Since atorvastatin is metabolized by CYP3A4 isoenzyme, concomitant use of atorvastatin with CYP3A4 isoenzyme inhibitors may lead to increased plasma concentration of atorvastatin. The degree of interaction and potentiation effect is determined by the variability of effects on CYP3A4 isoenzyme.

It was found that potent inhibitors of CYP3A4 isoenzyme lead to a significant increase in plasma concentration of atorvastatin. Concomitant use of potent CYP3A4 isoenzyme inhibitors (such as cyclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, pozaconazole, some antiviral drugs used in the therapy of viral hepatitis C (e.g., elbasvir/razoprevirHIV protease inhibitors, including ritonavir, lopinavir<(e.g., lopinavir, atazanavir, indinavir, darunavir, etc.).). If simultaneous use of these drugs is necessary, the possibility to begin therapy with minimal dose should be considered, and also the possibility to decrease maximal dose of atorvastatin should be assessed.

Moderate CYP3A4 isoenzyme inhibitors (e.g., erythromycin, diltiazem, verapamil and fluconazole) may lead to increased plasma concentrations of atorvastatin. Against the background of concomitant use of HMG-CoA reductase inhibitors (statins) and erythromycin an increased risk of myopathy was noted. Studies on the interaction of amiodarone or verapamil and atorvastatin have not been conducted. It is known that both amiodarone and verapamil inhibit the activity of CYP3A4 isoenzyme, and simultaneous use of these drugs with atorvastatin may lead to increased exposure of atorvastatin. In this regard, it is recommended to reduce the maximum dose of atorvastatin and conduct appropriate monitoring of the patient when concomitant use with moderate inhibitors of CYP3A4 isoenzyme. Monitoring should be performed after initiation of therapy and against the background of CYP3A4 isoenzyme inhibitor dose changes.

OATP1B1 transport protein inhibitors

Atorvastatin is metabolized by cytochrome P450 3A4 (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, the drug multidrug resistance transport protein 1, and the BCRP protein, which may limit the intestinal absorption and hepatic clearance of atorvastatin(see section “Pharmacological properties. Pharmacokinetics“).

OATP1B1 inhibitors (for example, cyclosporin) may increase bioavailability of atorvastatin. Thus, concomitant 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 plasma concentration of atorvastatin by 7.7 times (see section “Dosage and administration”). The effect of inhibition of hepatic capture transporter function on atorvastatin concentration in hepatocytes is unknown. If it is impossible to avoid concomitant use of such drugs, it is recommended to reduce the dose and control the effectiveness of therapy.

Gemfibrozil/fibrates

In the background of using fibrates in monotherapy, adverse reactions involving the musculoskeletal system, including rhabdomyolysis, have occasionally been noted. The risk of such reactions increases with concomitant use of fibrates and atorvastatin. If concomitant use of these drugs cannot be avoided, the lowest effective dose of atorvastatin should be used, and patients should be monitored regularly.

Ezetimibe

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

Eritromycin/Clarithromycin

When concomitant administration of atorvastatin and erythromycin (500 mg 4 times daily) or clarithromycin (500 mg 2 times daily), CYP3A4 isoenzyme inhibitors, increased concentration of atorvastatin in plasma was observed (see section “Special indications”).

Protease inhibitors

The concomitant use of atorvastatin with protease inhibitors, known as CYP3A4 isoenzyme inhibitors, is accompanied by an increase in plasma atorvastatin concentration.

Diltiazem

The concomitant use of atorvastatin at a dose of 40 mg with diltiazem at a dose of 240 mg leads to an increase in plasma concentration of atorvastatin.

Cimetidin

no clinically significant interaction of atorvastatin with cimetidin was found.

Itraconazole

The simultaneous use of atorvastatin at doses of 20 mg to 40 mg and itraconazole at 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) may cause an increase in plasma concentration of atorvastatin.

Transport protein inhibitors

Atorvastatin is a substrate of liver enzyme transporters, OATP1B1 and OATP1B3 transporters. Metabolites of atorvastatin are substrates of OATP1B1. Atorvastatin is also identified as a substrate of efflux transporters MDR1 and BCRP, which may limit intestinal absorption and biliary clearance of atorvastatin (see section “Pharmacological properties. Pharmacokinetics“).

Simultaneous use of atorvastatin at a dose of 10 mg and cyclosporine at a dose of 5.2 mg/kg/day resulted in increased systemic exposure to atorvastatin (AUC increase of 8.7 times) (see “Pharmacological properties. Pharmacokinetics“). Cyclosporine is an inhibitor of transport polypeptide of organic anions 1B1 (OATP1B1), 1B3 (OATP1BZ), MDL1 and BCRP-associated protein and CYP3A4 isoenzyme, therefore, it increases the systemic exposure of atorvastatin. The daily dose of atorvastatin should not exceed 10 mg (see section “Dosage and administration”).

Glecaprevir and pibrentasvir are inhibitors of OATP1B1, OATP1BZ, MLU1 and BCRP; therefore, they increase the level of atorvastatin exposure. The daily dose of atorvastatin should not exceed 10 mg (see section “Dosage and administration”).

Elbasvir and grazoprevir are inhibitors of OATP1B1, OATP1BZ, MLU1 and BCRP; therefore, they increase systemic exposure to atorvastatin. The drug Atoris^® should be used with caution and in the lowest dose necessary (see section “Dosage and administration”).

Inductors of CYP3A4 isoenzyme

Simultaneous use of atorvastatin with CYP3A4 isoenzyme inducers (e.g., efavirenz, rifampicinSt. John’s Wort) may lead to a decrease in plasma concentration of atorvastatin. Due to the dual mechanism of interaction with rifampicin (inducer of CYP3A4 isoenzyme and inhibitor of hepatocyte transport protein OATP1B1), simultaneous use of atorvastatin and rifampicin is recommended, since delayed administration of atorvastatin after rifampicin administration leads to a significant decrease in plasma concentration of atorvastatin. However, the effect of rifampicin on atorvastatin concentration in hepatocytes is unknown, and if concomitant use cannot be avoided, the effectiveness of such a combination should be carefully monitored during therapy.

Antacids

Concomitant oral administration of suspension containing magnesium hydroxide or aluminum hydroxide decreased plasma concentration of atorvastatin by approximately 35%, but the degree of decrease in plasma concentration of LDL-C did not change.

Phenazone

Atorvastatin does not affect the pharmacokinetics of phenazone, so no interaction with other drugs metabolized by the same cytochrome system isoenzymes is expected.

Colestipol

Concomitant use of colestipol decreased plasma concentration of atorvastatin by approximately 25%, but the hypolipidemic effect of combining atorvastatin and colestipol was superior to that of each drug alone.

Digoxin

The equilibrium plasma concentrations of digoxin and atorvastatin at a dose of 10 mg did not change when digoxin and atorvastatin were administered again. However, when digoxin was used in combination with atorvastatin at a dose of 80 mg/day, digoxin concentrations increased by approximately 20%. Patients receiving digoxin concomitantly with atorvastatin require appropriate monitoring.

Asithromycin

The plasma concentrations of atorvastatin at a dose of 10 mg once daily and azithromycin at a dose of 500 mg once daily did not change.

Orral contraceptive drugs

The concomitant use of atorvastatin and oral contraceptive drugs containing norethisterone and ethinylestradiol showed 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

No clinically significant changes in terfenadine pharmacokinetics were observed with concomitant use of atorvastatin and terfenadine.

Varfarin

In a clinical study in patients receiving regular warfarin therapy, concomitant use of atorvastatin at a dose of 80 mg daily 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. Despite the fact that only in rare cases significant interaction affecting anticoagulant function was observed, it is necessary to determine prothrombin time before atorvastatin therapy in patients receiving coumarin anticoagulants therapy, and regularly – during the therapy to prevent its significant change. Once prothrombin time has stabilized, it can be monitored in the same manner as recommended for patients receiving coumarin anticoagulants. If the dose of atorvastatin is changed or therapy is discontinued, prothrombin time should be controlled according to the same principles as described above. Therapy with atorvastatin has not been associated with the development of bleeding or changes in prothrombin time in patients who were not treated with anticoagulants.

Colchicine

Although there have been no studies of concomitant use of colchicine and atorvastatin, there have been reports of myopathy with this combination. Caution should be exercised when concomitant use of atorvastatin and colchicine.

Amlodipine

The pharmacokinetics of atorvastatin at a dose of 80 mg and amlodipine at a dose of 10 mg were not altered in equilibrium.

Fusidic acid

In post-marketing studies, cases of rhabdomyolysis have been reported in patients taking statins, including atorvastatin and fusidic acid, simultaneously. The mechanism of this interaction is unknown. In patients for whom the use of fusidic acid is considered necessary, statin therapy should be discontinued for the duration of fusidic acid use. Therapy with statins may be resumed 7 days after the last fusidic acid administration. In exceptional cases, when prolonged systemic therapy with fusidic acid is necessary (e.g., 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 be under the strict supervision of a physician. The patient should be advised to seek immediate medical attention if symptoms such as muscle weakness, sensitivity, or pain occur.

Other related therapy

In clinical trials, atorvastatin was used concomitantly with hypotensive agents and estrogens as part of hormone replacement therapy. No signs of clinically significant adverse interactions have been observed; no studies on the interaction with specific drugs have been conducted.

In addition, increased concentrations of atorvastatin have been noted when used concomitantly with HIV protease inhibitors (combinations oflopinavir and ritonavir, saquinavir and ritonavir, darunavir and ritonavir, , as well as combinations of fosamprenavira/em>with ritonavir and nelfinavir), viralhepatitis C (boseprevir), clarithromycin and itraconazole. Caution should be exercised when using these drugs concomitantly, and the lowest effective dose of atorvastatin should be used.

Special Instructions

In patients with the presence of risk factors for rhabdomyolysis (impaired renal function, hypothyroidism, hereditary muscle disorders in a patient in the history or in the family history, already suffered toxic effects of HMG-CoA reductase inhibitors [statins] or fibrates on muscle tissue, history of liver disease and/or use in patients consuming significant amounts of alcohol, age over 70 years, situations in which atorvastatin plasma concentrations are expected to increase [e.g., interactions with other medicinal products]).

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

Application in children 10 to 18 years of age in heterozygous familial hypercholesterolemia

For patients with heterozygous familial hypercholesterolemia aged 10 years or older, the recommended starting dose of atorvastatin is 10 mg daily. The dose may be increased to 80 mg daily depending on response and tolerability. The dose should be adjusted individually according to the recommended therapy. Adjustments may be made at intervals of 4 weeks or more. Recommendations for dose titration up to 80 mg daily are based on data from studies involving adult patients and limited data from clinical trials involving children with heterozygous familial hypercholesterolemia.

Atorvastatin-treated children aged 10 to 17 years had an adverse event profile similar to that of patients receiving placebo, with infections being the most common adverse event in both groups, regardless of causality assessment. No clinically significant effects on growth and puberty were observed in the 3-year study (as measured by general maturation and development, Tanner pubertal stage assessment, and height and body weight measurements). 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 receiving atorvastatin, among whom 7 patients were aged < 6 years, 121 patients were aged 6 to 9 years, and 392 patients were aged 10 to 17 years. Based on the available data, the incidence, type, and severity of adverse reactions in children were similar to those in adults.

In an 8-week open-label study, children (ages 6-17 years) with heterozygous familial hypercholesterolemia and baseline LDL-C concentrations ≥4 mmol/L received atorvastatin therapy as 5 mg or 10 mg chewable tablets or film-coated tablets at a dose of 10 mg or 20 mg once daily, respectively. The only significant covariate in the pharmacokinetic model of the population receiving atorvastatin 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 atorvastatin and o-hydroxyatorvastatin there was a consistent decrease in LDL-C and CHD.

Liver function impairment

In patients with impaired liver function, the dose of Atoris^® should be decreased with regular monitoring of serum alanine transaminase (ACT) and alanine aminotransferase (ALT) activity.

Kidney function impairment

Renal dysfunction does not affect atorvastatin concentration or the degree of reduction of plasma LDL-C concentration, therefore no dose adjustment is required.

Elderly patients

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

Impact on the liver

As with other hypolipidemic agents of this class, a moderate increase (more than 3 times the upper limit of normal) in plasma ACT and ALT values was observed during treatment with atorvastatin. A persistent increase (more than 3 times the upper limit of normal) was observed in 0.7% of patients treated with atorvastatin. Frequency of similar changes while using Atorvastatin in doses of 10 mg, 20 mg, 40 mg and 80 mg was 0.2%, 0.2%, 0.6% and 2.3%, respectively. Elevation of “hepatic” transaminases activity in blood plasma was usually not accompanied with jaundice or other clinical manifestations. When the dose of atorvastatin was decreased, temporarily or completely discontinued, plasma hepatic transaminase activity returned to the initial level. Most patients continued taking atorvastatin in a reduced dose without any clinical consequences.

Before the start of therapy, 6 weeks and 12 weeks after the start of Atoris^® or after increasing its dose liver function parameters should be controlled. Liver function should also be monitored when clinical signs of liver damage appear. In case of increased activity of “hepatic” transaminases in plasma, the activity of ALT and ACT in plasma should be monitored until they normalize. If the increase of ACT or ALT activity in plasma remains more than 3 times the upper limit of normal, it is recommended to reduce the dose or discontinue Atoris^® (see 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 persistently elevated activity of “hepatic” plasma transaminases of unclear genesis are contraindications to the use of Atoris^® (see section “Contraindications”).

Action on skeletal muscles

Myalgia has been reported in patients receiving atorvastatin (see 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). Atoris^® therapy should be discontinued in case of marked increase of serum CPK, in presence of confirmed or suspected myopathy. The risk of myopathy during treatment with this class of drugs was increased when concomitant use of potent CYP3A4 isoenzyme inhibitors (e.g., cyclosporine, telithromycin, clarithromycin, delavirdine, The use of the following inhibitors of the CYP3A4 isoenzyme (e.g., cyclosporine, cyclothromycin, clarithromycin, delavirdine, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors, including ritonavir, lopinavir, atazanavir, indinavir, Darunavir, tipranavir/ritonavir, etc.)), gemfibrozil or other fibrates, boceprevir, erythromycin, lipid-lowering nicotinic acid (more than 1 g per day), ezetimibe, azole antifungals, colchicine, antiviral agents used to treat viral hepatitis C (telaprevir, boceprevir or elbasvir/grazoprevir). Many of these drugs inhibit CYP3A4 isoenzyme-mediated metabolism and/or drug transport. It is known that 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 daily), a physician should carefully evaluate the ratio of expected treatment benefit to possible risk. Patients should be regularly monitored to detect muscle pain or weakness, especially during the first months of therapy and during the period of increasing the dose of any of the mentioned drugs. If combined therapy is necessary, consideration should be given to using lower initial and maintenance doses of the aforementioned agents. Concomitant use of atorvastatin and fusidic acid is not recommended, therefore temporary withdrawal of atorvastatin is recommended during treatment with fusidic acid. In such situations, periodic monitoring of CPK index may be recommended, although such monitoring does not prevent the development of severe myopathy (see section “Interaction with other medicinal products”).

Before treatment

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

• kidney function disorder;
• hypothyroidism;
• hereditary muscle disorders in the patient’s history or family history;
• >successful toxic effects of HMG-CoA reductase inhibitors (statins) or fibrates on muscle tissue;
• having a history of liver disease and/or patients with significant alcohol consumption;
• Patients aged over 70 years old should be evaluated for the necessity of serum CPK control, considering that these patients usually already have factors predisposing to rhabdomyolysis;
• situations in which atorvastatin plasma concentrations are expected to increase, such as interactions with other drugs (see

In these situations the risk/benefit ratio should be assessed and the patient’s condition should be monitored.

To avoid initiate atorvastatin therapy if serum CPK is significantly elevated (>5 times the upper limit of normal).

Atoris^®, like other HMG-CoA reductase inhibitors, has described rare cases of rhabdomyolysis with acute renal failure due to myoglobinuria. Prior renal dysfunction may be a risk factor for rhabdomyolysis. Such patients should be closely monitored in the musculoskeletal system. If there are symptoms of myopathy or risk factors of renal failure against the background of rhabdomyolysis (for example, severe acute infection, arterial hypotension, extensive surgery, trauma, metabolic, endocrine and electrolyte disorders, uncontrolled convulsions) Atoris^® therapy should be temporarily stopped or completely stopped.

Very rare cases of immune-mediated necrotizing myopathy during therapy or upon discontinuation of statins have been reported. Immune-mediated necrotizing myopathy is clinically characterized by persistent proximal muscle weakness and elevated serum CPK activity that persists despite discontinuation of statin treatment.

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

Prevention of stroke by actively reducing plasma concentrations of CHC(SPARCL)

In a retrospective analysis of stroke subtypes, patients without CHD who had recently had a stroke or TIA and initially received atorvastatin at a dose of 80 mg had a higher incidence of hemorrhagic stroke compared with patients receiving placebo. The increased risk was particularly marked in patients with a history of hemorrhagic stroke or lacunar infarction at baseline. In this group of patients, the benefit/risk ratio when taking atorvastatin at a dose of 80 mg has not been determined sufficiently, therefore, the possible risk of hemorrhagic stroke in these patients should be carefully evaluated before starting therapy.

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

Diabetes

Some evidence supports that HMG-CoA reductase inhibitors (statins) as a class can lead to elevated plasma glucose concentrations, and individual patients at high risk for diabetes may develop a state of hyperglycemia requiring correction as in diabetes mellitus. However, this risk does not exceed the benefit of therapy with HMG-CoA reductase inhibitors (statins) in terms of vascular risks, so it may not be a reason to discontinue therapy. Patients related to the risk group (fasting blood glucose concentration from 5.6 to 6.9 mmol/l, BMI > 30 kg/m2 body surface area, increased concentration of TG in plasma, arterial hypertension) should be under medical control including control of biochemical blood parameters according to the National guidelines.

Interstitial lung disease

Anecdotal cases of interstitial lung disease have been reported during therapy with some HMG-CoA reductase inhibitors (statins), especially during long-term therapy. Dyspnea, non-productive cough and deterioration of general health (fatigue, weight loss and fever) may be observed. If interstitial lung disease is suspected in a patient, atorvastatin therapy should be stopped.

Endocrine function

In the use of HMG-CoA reductase inhibitors (statins), including atorvastatin, there have been cases of increased HbA1 and fasting blood glucose concentrations. Nevertheless, the risk of hyperglycemia is lower than the degree of reduction of risk of vascular complications against the background of taking HMG-CoA reductase inhibitors (statins).

Application in children

In a 3-year study, no clinically significant effects on growth and puberty were observed (as measured by general maturation and development, Tanner’s pubertal stage assessment, and height and body weight measurements).

Special infopinformation on excipients

Atoris^® contains lactose; therefore it 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 hazardous activities that require increased concentration and rapid psychomotor reactions. However, taking into account the possibility of dizziness, caution should be exercised when performing the above activities.

Synopsis

tablets 30 mg:

Circular, slightly biconvex film-coated tablets, white or almost white, with bevel.

tablets 60 mg:

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

tablets 80 mg:

Capsule-shaped, biconvex film-coated tablets, white or nearly white.

Contraindications

• High sensitivity to any component of the product.
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.0001pt; mso-add-space: auto; text-align: justify; mso-list: l2 level1 lfo1;”>Active liver disease or elevated plasma “liver” transaminases of unclear origin more than 3 times the upper limit of normal activity.
• Simultaneous use with fusidic acid.
• The use of antiviral agents designed to treat viral hepatitis C, glecaprevir/pibrentasvir.
• Pregnancy.
• Breastfeeding
• Women of childbearing age who are not using adequate methods of contraception.
• Age under 18 years of age (insufficient clinical data on efficacy and safety in this age group), except for heterozygous familial hypercholesterolemia (use contraindicated in children under 10 years).

Side effects

The drug Atoris^® is usually well tolerated, adverse reactions are usually mild and transient.

World Health Organization (WHO) recommended side effect frequency classification:

very often ≥ 1/10

often from ≥1/100 to < 1/10

infrequently from ≥ 1/1000 to < 1/100

rarely from ≥ 1/10000 to < 1/1000

very rarely < 1/10000

frequency is unknown cannot be estimated from available data.

Infectious and parasitic diseases:

often: nasopharyngitis.

Blood and lymphatic system disorders:

rare: thrombocytopenia.

immune system disorders:

often: allergic reactions;

very rarely: anaphylaxis.

Disorders of metabolism and nutrition:

often: hyperglycemia;

infrequently: hypoglycemia, weight gain, anorexia;

incidence unknown: diabetes mellitus – incidence depends on the presence or absence of risk factors (fasting blood glucose concentration ≥ 5.6 mmol/L, body mass index [BMI] > 30 kg/m² body surface area, elevated plasma TG concentration, history of hypertension).

Mental disorders:

infrequent: “nightmare” dreams, insomnia;

frequency unknown: depression.

Nervous system disorders:

infrequent: dizziness, paresthesia, hypoesthesia, taste disorder, amnesia;

rarely: peripheral neuropathy;

frequency unknown: loss or reduction of memory.

Visual disorders:

infrequent: the appearance of “shadows” before the eyes;

rare: visual disturbances.

Hearing organ and labyrinth disorders:

infrequent: tinnitus;

very rare: hearing loss.

Disorders of the respiratory system, thoracic and mediastinal organs:

often: sore throat, nasal bleeding;

frequency unknown: single cases of interstitial lung disease (usually with long-term use).

digestive system disorders:

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

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

Liver and biliary tract disorders:

infrequent: hepatitis;

rare: cholestasis.

Skin and subcutaneous tissue disorders:

seldom: angioneurotic edema, bullous rash, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Muscular and connective tissue disorders:

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

very rare: lupus-like syndrome;

frequency unknown: immune-mediated necrotizing myopathy.

Kidney and urinary tract disorders:

very rare: secondary renal failure.

Gender and breast disorders:

infrequently: impotence;

very rarely: gynecomastia.

General disorders and disorders at the site of administration:

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

Laboratory and instrumental findings:

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

infrequent: leukocyturia;

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

children

Atorvastatin-treated children aged 10 to 17 years had an adverse event profile similar to that of patients receiving placebo, with infections being the most common adverse event in both groups, regardless of causality assessment. No clinically significant effects on growth and puberty were observed in the 3-year study (as measured by general maturation and development, Tanner pubertal stage assessment, and height and body weight measurements). 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 receiving atorvastatin, among whom 7 patients were aged < 6 years, 121 patients were aged 6 to 9 years, and 392 patients were aged 10 to 17 years. Based on the available data, the incidence, type, and severity of adverse reactions in children were similar to those in adults.

Overdose

There is no specific antidote for 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 CPK should be monitored. Since atorvastatin is actively bound to blood plasma proteins, hemodialysis is ineffective.

Pregnancy use

The drug Atoris^® is contraindicated in pregnancy.

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

Rare cases of congenital abnormalities have been reported following fetal exposure to HMG-CoA reductase inhibitors (statins). Toxic effects on reproductive function have been shown in animal studies. Atoris^® is contraindicated during lactation. It is unknown whether atorvastatin is excreted with breast milk. If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped to avoid the risk of adverse effects in infants.

Similarities

Liprimar, Atoris, Tulip, Atorvastatin, Torvacard, Atorvastatin NW , Atorvastatin-Teva