Atorvastatin pills 20mg №90

pharmachologic effect

Lipid-lowering agent from the group of statins. According to the principle of competitive antagonism, the statin molecule binds to the 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 product in the synthesis of the cholesterol molecule. Inhibition of the activity of HMG-CoA reductase leads to a series of consecutive reactions, which result in a decrease in the intracellular cholesterol content and a compensatory increase in the activity of LDL receptors and, accordingly, an acceleration of cholesterol catabolism (Xc) of LDL.

The lipid-lowering effect of statins is associated with a decrease in total Xc due to Xc-LDL. A decrease in the level of LDL is dose-dependent and is not linear, but exponential. The inhibitory effect of atorvastatin on HMG-CoA reductase by about 70% is 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 indirectly through their main effects on reducing the level of Xc-LDL.A moderate decrease in the level of TG in the treatment with statins seems to be associated with the expression of the remnant (apo E) receptors on the surface of hepatocytes involved in the catabolism of LPPP, which are approximately 30% TG. Compared with other statins (with the exception of rosuvastatin), atorvastatin causes a more pronounced decrease in TG levels.

In addition to the lipid-lowering action, statins have a positive effect on endothelial dysfunction (preclinical sign of early atherosclerosis), on the vascular wall, atheroma, improve the rheological properties of blood, have antioxidant, anti-proliferative properties.

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

Pharmacokinetics

Atorvastatin is rapidly absorbed from the gastrointestinal tract. Absolute bioavailability is low - about 12%, due to presystemic clearance in the gastrointestinal mucosa and / or as a result of "first passage" through the liver, mainly in the site of action.

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

T_1/2 from plasma is about 14 h although T_1/2 inhibitor of HMG-CoA reductase activity is approximately 20-30 hours, due to the participation of active metabolites.

Plasma protein binding is 98%.

Atorvastatin is excreted in the form of metabolites predominantly with bile.

Indications

Primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia (Fredrikson's type IIa), combined (mixed) hyperlipidemia (Fredrickson's type IIa and IIb), dysbetalipoproteinemia (Fredrikson type III) (as appropriate, as the 74, Fredrikson's category, and as the application, (as the application for the Fredrickson classification) (as the application, and as the application for the Fredrikson classification, you can use the Fredrickson family, and you can use it (as an application for the Fredrickson family)) (type IV according to Fredrickson's classification), resistant to diet; homozygous familial hypercholesterolemia with insufficient efficacy of diet therapy and other non-pharmacological methods of treatment Nia.

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 old, nicotine dependence, arterial hypertension, diabetes mellitus, low concentrations of Xc-HDL in plasma, genetic predisposition, in t. h against 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 and the need for revascularization.

Dosing regimen

The treatment is carried out against the background of a standard diet for patients with hypercholesterolemia. Dose set individually, depending on the initial level of cholesterol. Is ingested. The initial dose is usually 10 mg 1 time / day. The effect appears within 2 weeks, and the maximum effect within 4 weeks.If necessary, the dose can be gradually increased with an interval of 4 weeks or more. The maximum daily dose is 80 mg.

Side effect

Nervous system: > 1% - insomnia, dizziness; <1% - headache, asthenia, malaise, drowsiness, nightmares, paresthesias, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesis, migraine, depression, hypoesthesia, loss of consciousness.

Special senses:<1% - amblyopia, tinnitus, dry conjunctiva, accommodation disturbance, retinal hemorrhage, deafness, glaucoma, parosmia, loss of taste, taste perversion.

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

Hemic and lymphatic:<1% - anemia, lymphadenopathy, thrombocytopenia.

Respiratory:> 1% - bronchitis, rhinitis; <1% - pneumonia, dyspnea, exacerbation of bronchial asthma, nosebleeds.

Gastrointestinal:> 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, abnormal liver function, rectal bleeding, melena, gingival bleeding, tenesmus.

Musculoskeletal system:> 1% arthritis; <1% - leg muscle spasms, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonia, joint contractures, joint swelling, tendinopathy (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, imperative urination to urinate), leukocyturia, nephritis, hematuria, vaginal bleeding, nephrorolithiasis, metrorrhagia, epididymitis, reduction of libido, myocardium, nephrorolithiasis, metrorrhagia, epididymitis, reduction of libido, myocardium, nephrorolithiasis, metrorrhagia, epididymitis, reduction of libido, myocardium, nephrorolithiasis, metrorrhagia, epididymitis, reduction of libido, myocardium, nephrorolithiasis, metrorrhagia, epididymitis, reduction of libido, myocardium, nephrorolithiasis, metrorrhagia, epididymitis, reduction of libido, myocardium

Dermatologic:> 1% - alopecia, xeroderma, photosensitization, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

On the part of the endocrine system: <1% - gynecomastia, mastodynia.

Metabolism: <1% - weight gain, exacerbation of gout.

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

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

Contraindications

Liver diseases in the active stage, increase in serum transaminase activity (more than 3 times compared to VGN) of unclear genesis, pregnancy,lactation (breastfeeding), women of reproductive age who do not use reliable contraceptives; children and adolescents under 18 years of age (there is insufficient clinical data on the efficacy and safety for this age group); hypersensitivity to atorvastatin.

Use 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 necessary, use of the drug during lactation should decide on the termination of breastfeeding.

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

Application for violations of the liver

Contraindication: liver disease in the active stage.

Before and during treatment with atorvastatin, especially when symptoms of liver damage appear, it is necessary to monitor 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 normal, is maintained, it is recommended to reduce the dose or cancel atorvastatin.

Use in children

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

special instructions

C caution should be used in patients who abuse alcohol; 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 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 normal, is maintained, it is recommended to reduce the dose or cancel atorvastatin.

When symptoms of myopathy appear during treatment, the activity of CPK should be determined. If a significant increase in the level of CPK is maintained, then it is recommended to reduce the dose or stop 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 possibility of the following adverse reactions, but not all cases have a clear connection with taking atorvastatin: muscle cramps, myositis, myopathy, paresthesia, peripheral neuropathy, pancreatitis, hepatitis, cholestatic jaundice, anorexia, vomiting, alopecia, pruritus, rash, impotence, hyperglycemia and hypoglycemia.

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

Atorvastatin is used with caution in patients with chronic alcoholism.

Drug interaction

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

Diltiazem, Verapamil , isradipine inhibit the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, therefore, with the simultaneous use of Calcium channels with these 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 significantly increases, apparently due to the inhibition by itraconazole of its metabolism in the liver, which occurs with the participation of the CYP3A4 isoenzyme; increased risk of myopathy.

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

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

With 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 CYP3A4 isoenzyme.