Atoris tablets p / o 30mg, No. 30

• Primary hypercholesterolemia (heterozygous familial and nonfamilial hypercholesterolemia (type IIa according to Fredrickson's classification);

• combined (mixed) hyperlipidemia (types IIa and IIb according to the Fredrickson classification);

• dysbetalipoproteinemia (type III according to the Fredrickson classification) (as a supplement to the diet); familial endogenous hypertriglyceridemia (type IV according to the Fredrickson classification), resistant to diet; homozygous familial hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological methods of treatment.

• Primary prevention of cardiovascular complications in patients without clinical signs of coronary artery disease, but with several risk factors for its development - age over 55 years, nicotine addiction, arterial hypertension, diabetes mellitus, low concentrations 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.

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

Treatment is carried out against the background of a standard diet for patients with hypercholesterolemia. The dose is set individually, depending on the initial cholesterol level. It is taken internally. The starting dose is usually 10 mg once a day. The effect appears within 2 weeks, and the maximum effect within 4 weeks. If necessary, the dose can be gradually increased at intervals of 4 weeks or more. The maximum daily dose is 80 mg.

Film-coated tablets, white, round, slightly biconvex; at the break there is a white mass with a rough surface.

1 tab.

Active ingredient: atorvastatin calcium - 31.08 mg, which corresponds to the content of atorvastatin - 30 mg

Excipients: lactose monohydrate - 175.24 mg, microcrystalline cellulose - 52.5 mg, hyprolose - 6 mg, croscarmellose sodium - 15 mg, crospovidone type A - 15 mg, polysorbate 80 - 680 ?g, sodium hydroxide - 1.5 mg, magnesium stearate - 3 mg ...

The composition of the film shell: opadry II HP 85F28751 white - 9 mg (polyvinyl alcohol - 3.6 mg, titanium dioxide (E171) - 2.25 mg, macrogol 3000 - 1.82 mg, talc - 1.33 mg).

• Active liver disease

• an increase in the activity of serum transaminases (more than 3 times compared with VGN) of unknown origin,

• pregnancy,

• lactation (breastfeeding),

• women of reproductive age who do not use reliable contraception;

• children and adolescents up to 18 years old;

• hypersensitivity to atorvastatin.

Clinical and pharmacological group: Lipid-lowering drug

Pharmaco-therapeutic group: Lipid-lowering agent - HMG-CoA reductase inhibitor

pharmachologic effect

Lipid-lowering agent from the statin group. According to the principle of competitive antagonism, the statin molecule binds to that part of the coenzyme A receptor where HMG-CoA reductase is attached. Another part of the statin molecule inhibits the conversion of hydroxymethylglutarate to mevalonate, an intermediate in the synthesis of the cholesterol molecule. Inhibition of the activity of HMG-CoA reductase leads to a series of sequential reactions, as a result of which the intracellular cholesterol content decreases and a compensatory increase in the activity of LDL receptors occurs and, accordingly, an acceleration of the catabolism of LDL cholesterol (Xc).

The lipid-lowering effect of statins is associated with a decrease in the level of total cholesterol due to LDL cholesterol. The decrease in LDL cholesterol is dose-dependent and not linear, but exponential. The inhibitory effect of atorvastatin on HMG-CoA reductase is approximately 70% determined by the activity of its circulating metabolites.

Statins do not affect the activity of lipoprotein and hepatic lipases, do not have a significant effect on the synthesis and catabolism of free fatty acids, therefore their effect on the TG level is secondary and is mediated through their main effects on lowering the level of LDL-C. A moderate decrease in the level of TG during treatment with statins, apparently, is associated with the expression of remnant (apo E) receptors on the surface of hepatocytes involved in the catabolism of DID, which comprise about 30% TG. Compared with other statins (with the exception of rosuvastatin), atorvastatin causes a more pronounced decrease in TG levels.

In addition to the hypolipidemic effect, statins have a positive effect on endothelial dysfunction (a preclinical sign of early atherosclerosis), on the vascular wall, the state of atheroma, improve the rheological properties of blood, have antioxidant, antiproliferative properties.

Atorvastatin lowers cholesterol levels in patients with homozygous familial hypercholesterolemia, which usually does not respond to lipid-lowering therapy.

Pharmacokinetics

Atorvastatin is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability is low - about 12%, which is due to presystemic clearance in the gastrointestinal mucosa and / or due to the 'first pass' through the liver, mainly at the site of action.

Atorvastatin is metabolized with the participation of the isoenzyme CYP3A4 with the formation of a number of substances that are inhibitors of HMG-CoA reductase.

T1 / 2 from plasma is about 14 hours, although T1 / 2 of the inhibitor of HMG-CoA reductase activity is about 20-30 hours, which is due to the participation of active metabolites.

Plasma protein binding is 98%.

Atorvastatin is excreted in the form of metabolites mainly in the bile.

Indications

• Primary hypercholesterolemia (heterozygous familial and nonfamilial hypercholesterolemia (type IIa according to Fredrickson's classification);

• combined (mixed) hyperlipidemia (types IIa and IIb according to the Fredrickson classification);

• dysbetalipoproteinemia (type III according to the Fredrickson classification) (as a supplement to the diet); familial endogenous hypertriglyceridemia (type IV according to the Fredrickson classification), resistant to diet; homozygous familial hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological methods of treatment.

• Primary prevention of cardiovascular complications in patients without clinical signs of coronary artery disease, but with several risk factors for its development - age over 55 years, nicotine addiction, arterial hypertension, diabetes mellitus, low concentrations 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.

Dosage regimen

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

Treatment is carried out against the background of a standard diet for patients with hypercholesterolemia. The dose is set individually, depending on the initial cholesterol level. It is taken internally. The starting dose is usually 10 mg once a day. The effect appears within 2 weeks, and the maximum effect within 4 weeks. If necessary, the dose can be gradually increased at intervals of 4 weeks or more. The maximum daily dose is 80 mg.

Side effect

From the nervous system: > 1% - insomnia, dizziness; <1% - headache, asthenia, malaise, drowsiness, nightmares, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesis, migraine, depression, hypesthesia, loss of consciousness.

From the senses: <1% - amblyopia, ringing in the ears, dryness of the conjunctiva, impaired accommodation, retinal hemorrhage, deafness, glaucoma, parosmia, loss of taste, taste perversion.

From the side of the cardiovascular system: > 1% - chest pain; <1% - palpitations, symptoms of vasodilation, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris.

From the hematopoietic system: <1% - anemia, lymphadenopathy, thrombocytopenia.

From the respiratory system: > 1% - bronchitis, rhinitis; <1% - pneumonia, dyspnea, exacerbation of bronchial asthma, epistaxis.

From the digestive system: > 1% - nausea; <1% - heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, liver dysfunction, rectal bleeding, melena, bleeding gums, tenesmus.

From the musculoskeletal system: > 1% - arthritis; <1% - leg muscle cramps, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonia, joint contractures, joint swelling, tendopathy (in some cases with tendon rupture).

From the genitourinary system: > 1% - urogenital infections, peripheral edema; <1% - dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, urgency to urinate), leukocyturia, nephritis, hematuria, vaginal bleeding, nephrourolithiasis, metrorrhagia, epididymitis, decreased libido, impotence, impaired ejaculation.

Dermatological reactions: > 1% - alopecia, xeroderma, photosensitivity, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

From the endocrine system: <1% - gynecomastia, mastodynia.

From the side of metabolism: <1% - an increase in body weight, exacerbation of gout.

Allergic reactions: <1% - pruritus, skin rash, contact dermatitis, rarely - urticaria, angioedema, facial edema, anaphylaxis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome) ...

Laboratory indicators: <1% - hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.

Contraindications for use

• Active liver disease

• an increase in the activity of serum transaminases (more than 3 times compared with VGN) of unknown origin,

• pregnancy,

• lactation (breastfeeding),

• women of reproductive age who do not use reliable contraception;

• children and adolescents up to 18 years old;

• hypersensitivity to atorvastatin.

Application during pregnancy and lactation

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

It is not known whether atorvastatin is excreted in breast milk. Given the possibility of adverse events in infants, if it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be resolved.

Women of reproductive age should use adequate contraceptive methods during treatment. Atorvastatin can be used in women of reproductive age only if the likelihood of pregnancy is very low, and the patient is informed about the possible risk of treatment for the fetus.

Application for violations of liver function

Contraindication: active liver disease.

Before and during treatment with atorvastatin, especially when symptoms of liver damage appear, it is necessary to monitor the indicators of liver function. With an increase in the level of transaminases, their activity should be monitored until normalization. If the activity of AST or ALT, more than 3 times higher than the norm, persists, it is recommended to reduce the dose or discontinue atorvastatin.

Application in children

In children, the experience of using atorvastatin at a dose of up to 80 mg / day is limited.

special instructions

Use with caution in patients with alcohol abuse; with indications of a history of liver disease.

Before and during treatment with atorvastatin, especially when symptoms of liver damage appear, it is necessary to monitor the indicators of liver function. With an increase in the level of transaminases, their activity should be monitored until normalization. If the activity of AST or ALT, more than 3 times higher than the norm, persists, it is recommended to reduce the dose or discontinue atorvastatin.

When symptoms of myopathy appear on the background of treatment, the activity of CPK should be determined. If a significant increase in the CPK level persists, then it is recommended to reduce the dose or cancel atorvastatin.

The risk of myopathy during treatment with atorvastatin increases with the simultaneous use of cyclosporine, fibrates, erythromycin, antifungal drugs related to azoles, and niacin.

There is a likelihood of the following adverse reactions, but not in all cases there is a clear connection with the intake of atorvastatin: muscle cramps, myositis, myopathy, paresthesia, peripheral neuropathy, pancreatitis, hepatitis, cholestatic jaundice, anorexia, vomiting, alopecia, pruritus, rash, impotence, hyperglycemia and hypoglycemia.

In children, the experience of using atorvastatin at a dose of up to 80 mg / day is limited.

Atorvastatin is used with caution in patients with chronic alcoholism.

Drug interactions

With the simultaneous use of atorvastatin with digoxin, the concentration of digoxin in the blood plasma slightly increases.

Diltiazem, verapamil, isradipine inhibit the isoenzyme CYP3A4, which is involved in the metabolism of atorvastatin, therefore, when used simultaneously with these calcium channel blockers, it is possible to increase the concentration of atorvastatin in the blood plasma and increase the risk of myopathy.

With the simultaneous use of itraconazole, the concentration of atorvastatin in the blood plasma increases significantly, apparently due to inhibition by itraconazole of its metabolism in the liver, which occurs with the participation of the isoenzyme CYP3A4; increased risk of developing myopathy.

With the simultaneous use of colestipol, it is possible to reduce the concentration of atorvastatin in the blood plasma, while the lipid-lowering effect is enhanced.

With the simultaneous use of antacids containing magnesium hydroxide and aluminum hydroxide, reduce the concentration of atorvastatin by about 35%.

With the simultaneous use of cyclosporine, fibrates (including gemfibrozil), antifungal drugs of azole derivatives, nicotinic acid, the risk of myopathy increases.

With the simultaneous use of erythromycin, clarithromycin, the concentration of atorvastatin in plasma moderately increases, the risk of myopathy increases.

With the simultaneous use of ethinyl estradiol, norethisterone (norethindrone), the concentration of ethinyl estradiol, norethisterone and (norethindrone) in the blood plasma slightly increases.

With the simultaneous use of protease inhibitors, the concentration of atorvastatin in the blood plasma increases, because protease inhibitors are inhibitors of the isoenzyme CYP3A4.

Storage conditions:

At a temperature not exceeding 25 C in the original packaging.
Keep out of the reach of children.

Shelf life:

2 years.
Do not use after the expiration date.

Vacation conditions

On prescription

Manufacturer

JSC 'KRKA, dd, Novo mesto', Smarjeska cesta 6, 8501, Novo mesto, Slovenia, Slovenia

Marketing Authorization Holder / Organization Receiving Consumer Claims:

JSC 'KRKA, dd, Novo mesto'