Atoris, 30 mg , 30 pcs.

1 tablet contains: 

Active substance: 

atorvastatin calcium - 31.08 mg (equivalent to 30 mg of atorvastatin, respectively).

Excipients:

lactose monohydrate - 175.24 mg;

MCC - 52.5 mg;

hyprolosis - 6;

croscarmellose sodium - 15 mg;

crospovidone, type A - 15 mg;

polysorbate 80 - 0.68 mg;

sodium hydroxide - 1.5 mg;

magnesium stearate - 3 mg.

Film casing:

Opadry II HP 85F28751 white (polyvinyl alcohol - 3.6 mg, titanium dioxide (E171) - 2.25 mg, macrogol 3000 - 1.82 mg, talc - 1.33 mg) - 9 mg.

Lipid-lowering drug from the statin group.

The main mechanism of action of atorvastatin is inhibition of the activity of HMG-CoA reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonic acid. This transformation is one of the early stages in the cholesterol (Xc) synthesis chain in the body. Suppression of Xc synthesis leads to increased reactivity of LDL receptors in the liver and extrahepatic tissues. These receptors bind LDL particles and remove them from the blood plasma, which leads to a decrease in the level of LDL-C in the blood.

The anti-atherosclerotic effect of the drug is manifested by the effect of atorvastatin on the walls of blood vessels and blood components. Atorvastatin inhibits the synthesis of isoprenoids, which are growth factors for the inner lining of blood vessels. Under the influence of atorvastatin, endothelium-dependent dilation of blood vessels improves, the content of LDL-C, apolipoprotein B, triglycerides decreases, the content of HDL-C and apolipoprotein A increases.

Atorvastatin reduces the viscosity of blood plasma and the activity of some factors of clotting and platelet aggregation. Thanks to this, it improves hemodynamics and normalizes the state of the coagulation system. HMG-CoA reductase inhibitors also have an effect on the metabolism of macrophages, block their activation and prevent rupture of atherosclerotic plaques.

As a rule, the therapeutic effect of atorvastatin develops after two weeks of using Atoris, and the maximum effect is achieved after 4 weeks.

Reliably reduces the risk of ischemic complications (including death from myocardial infarction) by 16%, the risk of re-hospitalization for angina pectoris accompanied by signs of myocardial ischemia - by 26%.

Pharmacokinetics

Suction

The absorption of atorvastatin is high, approximately 80% is absorbed from the gastrointestinal tract. The degree of absorption and concentration in blood plasma increase in proportion to the dose. The time to reach Cmax is, on average, 1-2 hours.

Food somewhat reduces the rate and duration of absorption of the drug (by 25% and 9%, respectively), but the decrease in LDL-C is similar to that when using atorvastatin without food.

The bioavailability of atorvastatin is low (12%), the systemic bioavailability of the inhibitory activity against HMG-CoA reductase is 30%. Low systemic bioavailability is due to first pass metabolism in the gastrointestinal tract mucosa and during the "first pass" through the liver.

Distribution

Average Vd - 381 l, binding to plasma proteins - more than 98%. Atorvastatin does not penetrate the BBB.

Metabolism

It is metabolized mainly in the liver under the action of the isoenzyme 3A4 of cytochrome P450 with the formation of pharmacologically active metabolites (ortho- and parahydroxylated derivatives, beta-oxidation products), which cause approximately 70% of the inhibitory activity against HMG-CoA reductase for 20-30 hours.

Withdrawal

T1 / 2 - 14 hours. It is excreted mainly in the bile (it does not undergo pronounced enterohepatic recirculation, it is not excreted during hemodialysis). About 46% is excreted in the feces, less than 2% in the urine.

Pharmacokinetics in special clinical situations

The differences in pharmacokinetics in patients by age and sex are insignificant and do not require dose adjustment.

In women, Cmax is 20% higher, AUC is 10% lower.

Pharmacokinetic studies in children have not been conducted.

Cmax and AUC of the drug in elderly patients (over 65 years old) are 40% and 30%, respectively, higher than those in young adult patients (it has no clinical significance).

Impaired renal function does not affect the concentration of atorvastatin in the blood plasma or its effect on lipid metabolism, therefore, a change in the dose of the drug in patients with impaired renal function is not required.

The concentration of the drug increases significantly (Cmax approximately 16 times, AUC approximately 11 times) in patients with alcoholic cirrhosis (class B according to the Child-Pugh classification).

Hyperlipidemia:

• primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia (type II according to Fredrickson);
• combined (mixed) hyperlipidemia (IIa and IIb types according to Fredrickson);
• dysbetalipoproteinemia (type III according to Fredrickson) (as an addition to the diet);
• familial endogenous hypertriglyceridemia (type IV according to Fredrickson), resistant to diet;
• homozygous familial hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological methods of treatment.

Prevention of cardiovascular diseases:

• primary prevention of cardiovascular complications in patients without clinical signs of ischemic heart disease, but with several risk factors for its development: age over 55 years, nicotine addiction, arterial hypertension, diabetes mellitus, low level of HDL-C in blood plasma, genetic predisposition, incl. h. against the background of dyslipidemia;
• secondary prevention of cardiovascular complications in patients with coronary artery disease in order to reduce the total mortality rate, myocardial infarction, stroke, re-hospitalization for angina pectoris and the need for revascularization.

Atoris® is contraindicated during pregnancy and during breastfeeding. Animal studies suggest that the risk to the fetus may outweigh any potential benefit to the mother.

In women of reproductive age who do not use reliable methods of contraception, the use of Atoris® is not recommended. When planning a pregnancy, it is necessary to stop using Atoris® at least 1 month before the planned pregnancy.

There is no information on the excretion of atorvastatin in breast milk. However, in some animal species, the concentration of atorvastatin in blood and breast milk is similar. If it is necessary to use the drug Atoris® during lactation, in order to avoid the risk of developing adverse events in infants, breastfeeding should be stopped.

• active liver disease (including active chronic hepatitis, chronic alcoholic hepatitis);
• liver failure;
• cirrhosis of the liver of various etiologies;
• increased activity of hepatic transaminases of unknown origin (> 3 times compared with VGN);
• skeletal muscle disease;
• pregnancy;
• lactation period (breastfeeding);
• age up to 18 years (efficacy and safety of use has not been established);
• lactase deficiency, lactose intolerance, glucose / galactose malabsorption syndrome;
• hypersensitivity to any component of the drug.

The drug should be prescribed with caution in case of alcoholism, liver disease in history.

From the side of the central nervous system and peripheral nervous system: headache, dizziness, asthenic syndrome, insomnia or drowsiness, nightmares, amnesia, paresthesia, peripheral neuropathy, emotional lability, ataxia, hyperkinesis, depression, hypesthesia, weakness, malaise.

From the senses: amblyopia, ringing in the ears, dryness of the conjunctiva, impaired accommodation, hemorrhage in the eyes, deafness, glaucoma, parosmia, loss of taste.

From the side of the CVS: palpitations, vasodilation, migraine, postural hypotension, increased blood pressure, phlebitis, arrhythmia, chest pain, vasculitis.

From the hematopoietic system: anemia, lymphadenopathy, thrombocytopenia.

From the respiratory system: bronchitis, rhinitis, dyspnea, bronchial asthma, nosebleeds.

From the digestive system: nausea, heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, anorexia or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, gastroenteritis, hepatitis, hepatic colic, cheilitis duodenal ulcer, pancreatitis, cholestatic jaundice, increased activity of liver enzymes, rectal bleeding, melena, bleeding gums, tenesmus.

From the musculoskeletal system: myalgia, arthralgia, back pain, joint swelling, myopathy, muscle cramps, myositis, rhabdomyolysis, tendopathy (in some cases with tendon rupture).

From the genitourinary system: urogenital infections, dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, urge to urinate), cystitis, hematuria, vaginal bleeding, uterine bleeding, urolithiasis, metrorrhagia, epididymitis, decreased libido , impotence, ejaculation disorder.

On the part of the skin: sweating, eczema, seborrhea, ecchymosis.

Allergic reactions: pruritus, skin rash, contact dermatitis, rarely urticaria, angioedema, anaphylaxis, exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Laboratory indicators: increased activity of serum CPK, increased activity of ALT, ACT, hyperglycemia, hypoglycemia.

Others: peripheral edema, weight gain, fatigue, fever.

Before starting therapy with Atoris®, the patient must be prescribed a standard cholesterol-lowering diet, which he must follow during the entire period of treatment.

An increase in the activity of liver enzymes in the blood serum can be observed during treatment with Atoris®. This increase is usually small and has no clinical significance. However, it is recommended to control the activity of hepatic enzymes in the blood serum before treatment, after 6 and 12 weeks and with an increase in the dose of atorvastatin. If there is a three-fold increase in ACT and / or ALT activity relative to VGN, treatment with Atoris® should be discontinued.

Atorvastatin can cause an increase in the activity of CPK and aminotransferases.

In women of reproductive age who do not use reliable contraception, the use of Atoris® is not recommended. If the patient is planning a pregnancy, she should stop taking Atoris® at least one month before the planned pregnancy.

Patients should be warned to see a doctor immediately if they develop unexplained muscle pain or weakness. Especially if they are accompanied by malaise or fever.

Treatment with Atoris® can cause myopathy, which is sometimes accompanied by rhabdomyolysis, leading to acute renal failure. The risk of this complication increases when one or more of the following drugs are taken simultaneously with Atoris®: fibric acid derivatives, niacin, cyclosporine, nefazodone, some antibiotics, antifungal agents from the azole group, HIV protease inhibitors.

In case of clinical manifestations of myopathy, it is recommended to determine the plasma concentration of CPK. With a 10-fold increase in the relative VGN activity of CPK, treatment with Atoris® should be discontinued.

There are reports of the development of atonic fasciitis against the background of the use of atorvastatin, however, the connection with the use of the drug is possible, but has not yet been proven, the etiology is unknown.

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

The drug Atoris® contains lactose, and therefore its use by patients with lactase deficiency, lactose intolerance and glucose-galactose malabsorption syndrome is contraindicated.

Influence on the ability to drive vehicles and work with mechanisms.

Given the possibility of dizziness development, care should be taken when driving vehicles and other technical devices that require an increased concentration of attention and speed of psychomotor reactions.

Inside, regardless of food intake.

Before starting the use of Atoris®, the patient should be transferred to a diet that reduces the concentration of lipids in the blood, which must be observed throughout the therapy with the drug. Before starting therapy, one should try to control hypercholesterolemia with exercise and weight loss in obese patients, as well as therapy for the underlying disease.

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

Atoris® can be taken once at any time of the day, but at the same time every day. The therapeutic effect is observed after 2 weeks of treatment, and the maximum effect develops after 4 weeks. Therefore, the dosage should not be changed earlier than 4 weeks after the start of the drug in the previous dose.

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

Primary (heterozygous hereditary and polygenic) hypercholesterolemia (type IIa) and mixed hyperlipidemia (type IIb): treatment begins with the recommended initial dose, which is increased after 4 weeks, depending on the patient's response. The maximum daily dose is 80 mg.

Homozygous hereditary hypercholesterolemia: the dose range is the same as for other types of hyperlipidemia. The initial dose is selected individually, depending on the severity of the disease. In most patients with homozygous hereditary hypercholesterolemia, the optimal effect is observed when using the drug in a daily dose of 80 mg (once). Atoris® is used as an adjunctive therapy to other methods of treatment (plasmapheresis) or as the main treatment, if therapy with other methods is not possible.

Special patient groups.

Elderly patients.

In elderly patients, the dose of Atoris® should not be changed.

Impaired renal function.

Does not affect the concentration of atorvastatin in blood plasma or the degree of decrease in the concentration of LDL-C when using atorvastatin, so a change in the dose of the drug is not required.

Liver dysfunction.

In patients with impaired liver function, caution is required (due to a slowdown in the elimination of the drug from the body). In such a situation, clinical and laboratory parameters should be carefully monitored (regular monitoring of ACT and ALT activity). With a significant increase in hepatic transaminases, the dose of Atoris® should be reduced or treatment should be discontinued.

Use in combination with other drugs.

If it is necessary to use it simultaneously with cyclosporine, the daily dose of Atoris® should not exceed 10 mg.

Symptoms: If myopathy develops followed by rhabdomyolysis and acute renal failure (a rare but severe side effect), the drug should be stopped immediately.

Treatment: the patient needs to enter a diuretic and sodium bicarbonate solution. If necessary, hemodialysis should be performed. Rhabdomyolysis can lead to hyperkalemia, which requires intravenous administration of calcium chloride or calcium gluconate, infusion of 5% dextrose (glucose) solution with insulin, and the use of potassium exchange resins. Since atorvastatin is largely bound to plasma proteins, hemodialysis is ineffective.

General measures: monitoring and maintaining vital functions of the body and preventing further absorption of the drug (gastric lavage, the appointment of activated charcoal or laxatives).

Before starting therapy with Atoris®, the patient must be prescribed a standard cholesterol-lowering diet, which he must follow during the entire period of treatment.

An increase in the activity of liver enzymes in the blood serum can be observed during treatment with Atoris®. This increase is usually small and has no clinical significance. However, it is recommended to control the activity of hepatic enzymes in the blood serum before treatment, after 6 and 12 weeks and with an increase in the dose of atorvastatin. If there is a three-fold increase in ACT and / or ALT activity relative to VGN, treatment with Atoris® should be discontinued.

Atorvastatin can cause an increase in the activity of CPK and aminotransferases.

In women of reproductive age who do not use reliable contraception, the use of Atoris® is not recommended. If the patient is planning a pregnancy, she should stop taking Atoris® at least one month before the planned pregnancy.

Patients should be warned to see a doctor immediately if they develop unexplained muscle pain or weakness. Especially if they are accompanied by malaise or fever.

Treatment with Atoris® can cause myopathy, which is sometimes accompanied by rhabdomyolysis, leading to acute renal failure. The risk of this complication increases when one or more of the following drugs are taken simultaneously with Atoris®: fibric acid derivatives, niacin, cyclosporine, nefazodone, some antibiotics, antifungal agents from the azole group, HIV protease inhibitors.

In case of clinical manifestations of myopathy, it is recommended to determine the plasma concentration of CPK. With a 10-fold increase in the relative VGN activity of CPK, treatment with Atoris® should be discontinued.

There are reports of the development of atonic fasciitis against the background of the use of atorvastatin, however, the connection with the use of the drug is possible, but has not yet been proven, the etiology is unknown.

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

The drug Atoris® contains lactose, and therefore its use by patients with lactase deficiency, lactose intolerance and glucose-galactose malabsorption syndrome is contraindicated.

Influence on the ability to drive vehicles and work with mechanisms.

Given the possibility of dizziness development, care should be taken when driving vehicles and other technical devices that require an increased concentration of attention and speed of psychomotor reactions.

Film-coated tablets.