Atorvastatin 20 mg 30 coated tablets

Primary hypercholesterolemia when diet therapy is ineffective; combined hypercholesterolemia and hypertriglyceridemia; heterozygous and homozygous familial hypercholesterolemia when diet therapy is ineffective.

Treatment is conducted against the background of a standard diet for patients with hypercholesterolemia. The dose is determined individually, depending on the initial cholesterol level. Administered orally. The initial dose is usually 10 mg once daily. The effect manifests within 2 weeks, and the maximum effect occurs 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.

1 tablet
atorvastatin calcium trihydrate 21.7 mg,
which corresponds to the content of atorvastatin 20 mg

Excipients: microcrystalline cellulose - 105.02 mg, pregelatinized corn starch - 105.02 mg, colloidal silicon dioxide - 0.76 mg, magnesium carbonate - 66 mg, magnesium stearate - 1.5 mg.

Composition of the tablet coating: Opadry II white (85F18422) - 9 mg, (polyvinyl alcohol - 40%, titanium dioxide - 25%, macrogol-3350 - 20.2%, talc - 14.8%).

Film-coated tablets 20 mg

Active liver disease; serum transaminase levels elevated more than 3 times the upper limit of normal of unclear origin; pregnancy; lactation (breastfeeding); women of reproductive age not using reliable contraceptive methods; hypersensitivity to atorvastatin.
Atorvastatin is contraindicated during pregnancy and lactation (breastfeeding).
It is unknown whether atorvastatin is excreted in breast milk. Considering the possibility of adverse effects in breastfed infants, if the drug is necessary during lactation, the issue of discontinuing breastfeeding should be addressed.

Women of reproductive age during treatment should use adequate contraceptive methods. Atorvastatin may be used in women of reproductive age only if the likelihood of pregnancy is very low, and the patient is informed of the potential risks of treatment to the fetus.
Contraindication: active liver disease.
Before starting and during treatment with atorvastatin, especially if symptoms of liver damage appear, liver function tests should be monitored. If transaminase levels are elevated, their activity should be monitored until normalization. If AST or ALT activity exceeds the normal range by more than 3 times, dose reduction or discontinuation of atorvastatin is recommended.
Experience with atorvastatin in children at doses up to 80 mg/day is limited.

Before starting and during treatment with atorvastatin, especially upon the appearance of symptoms of liver damage, liver function tests must be monitored. If transaminase levels are elevated, their activity should be monitored until normalization. If the activity of AST or ALT exceeds the norm by more than three times, it is recommended to reduce the dose or discontinue atorvastatin.
If symptoms of myopathy occur during treatment, the activity of CK should be determined. If there is a significant increase in CK levels, it is recommended to reduce the dose or discontinue atorvastatin.
The risk of myopathy during treatment with atorvastatin is increased with the concomitant use of cyclosporine, fibrates, erythromycin, antifungal agents belonging to the azole class, and niacin.
There is a possibility of developing the following side effects; however, a clear relationship with atorvastatin use has not been established in all cases: muscle cramps, myositis, myopathy, paresthesia, peripheral neuropathy, pancreatitis, hepatitis, cholestatic jaundice, anorexia, vomiting, alopecia, itching, rash, impotence, hyperglycemia, and hypoglycemia.

In children, experience with atorvastatin at doses up to 80 mg/day is limited.
Atorvastatin should be used with caution in patients with chronic alcoholism.

Nervous system: > 1% - insomnia, dizziness; < 1% - headache, asthenia, malaise, drowsiness, vivid dreams, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, facial nerve paralysis, hyperkinesia, migraine, depression, hypesthesia, loss of consciousness. Sensory organs: 1% - chest pain; < 1% - palpitations, symptoms of vasodilation, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris. Hematopoietic system: 1% - bronchitis, rhinitis; 1% - nausea; 1% - arthritis; 1% - urogenital infections, peripheral edema; 1% - alopecia, xeroderma, photosensitivity, increased sweating, eczema, seborrhea, ecchymosis, petechiae.
Endocrine system: < 1% - gynecomastia, mastodynia. Metabolic disorders: < 1% - weight gain, exacerbation of gout. Allergic reactions: < 1% - skin itching, skin rash, contact dermatitis, rarely - urticaria, angioedema, facial swelling, anaphylaxis, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome). Laboratory indicators: < 1% - hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.When atorvastatin is used concurrently with digoxin, the concentration of digoxin in the plasma is slightly increased.Diltiazem, verapamil, and izradipine inhibit the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin; therefore, when used concurrently with these calcium channel blockers, an increase in the concentration of atorvastatin in the plasma and an increased risk of developing myopathy may occur.When itraconazole is used concurrently, the concentration of atorvastatin in the plasma significantly increases, apparently due to the inhibition of its metabolism in the liver by itraconazole, which occurs with the participation of the CYP3A4 isoenzyme; this increases the risk of developing myopathy.When colestipol is used concurrently, a decrease in the concentration of atorvastatin in the plasma may occur, while the hypolipidemic effect is enhanced.When antacids containing magnesium hydroxide and aluminum hydroxide are used concurrently, the concentration of atorvastatin is reduced by approximately 35%.When cyclosporine, fibrates (including gemfibrozil), azole derivative antifungal agents, and nicotinic acid are used concurrently, the risk of developing myopathy is increased.When erythromycin and clarithromycin are used concurrently, the concentration of atorvastatin in the plasma is moderately increased, raising the risk of developing myopathy.When ethinylestradiol and norethisterone (norethindrone) are used concurrently, the concentration of ethinylestradiol and norethisterone (norethindrone) in the plasma is slightly increased.When protease inhibitors are used concurrently, the concentration of atorvastatin in the plasma is increased, as protease inhibitors are inhibitors of the CYP3A4 isoenzyme.

Hypolipidemic agent from the statin group. By the principle of competitive antagonism, the statin molecule binds to the part of the coenzyme A receptor where HMG-CoA reductase attaches. Another part of the statin molecule inhibits the conversion of hydroxymethylglutaryl-CoA to mevalonate, an intermediate product in the synthesis of the cholesterol molecule. Inhibition of HMG-CoA reductase activity leads to a series of sequential reactions, resulting in a decrease in intracellular cholesterol content and a compensatory increase in LDL receptor activity, thereby accelerating the catabolism of cholesterol (Xc) in LDL.

The hypolipidemic effect of statins is associated with a reduction in total cholesterol levels due to LDL cholesterol. The reduction in LDL levels is dose-dependent and exhibits a non-linear, exponential nature. 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, and do not have a significant impact on the synthesis and catabolism of free fatty acids; therefore, their influence on triglyceride levels is secondary and mediated through their primary effects of reducing LDL cholesterol levels. The moderate reduction in triglyceride levels during statin treatment is apparently related to the expression of remnant (apo E) receptors on the surface of hepatocytes, which are involved in the catabolism of VLDL, of which approximately 30% is triglycerides. Compared to other statins (except rosuvastatin), atorvastatin causes a more pronounced reduction in triglyceride levels.

In addition to its hypolipidemic action, 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, and possess antioxidant and antiproliferative properties.

Atorvastatin reduces cholesterol levels in patients with homozygous familial hypercholesterolemia, which is usually resistant to treatment with hypolipidemic agents.

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 as a result of first-pass metabolism in the liver, primarily at the site of action.
Atorvastatin is metabolized with the involvement of the isoenzyme CYP3A4, resulting in the formation of several substances that are inhibitors of HMG-CoA reductase.
The half-life (T1/2) from plasma is approximately 14 hours, although the half-life of the HMG-CoA reductase activity inhibitor is about 20-30 hours, which is due to the involvement of active metabolites.
The binding to plasma proteins is 98%.
Atorvastatin is excreted in the form of metabolites primarily in bile.