Liprimar pills 80mg №30

Lipid-lowering drug

pharmachologic effect

Synthetic lipid-lowering drug. Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, a key enzyme that converts 3-hydroxy-3-methylglutaryl-CoA into mevalonate, the precursor of steroids, including cholesterol.

In patients with homozygous and heterozygous familial hypercholesterolemia, non-family forms of hypercholesterolemia and mixed dyslipidemia, atorvastatin reduces plasma content of total cholesterol (TC), LDL-C, and apolipoprotein B (apo-B), as well as the content of Xe-VLDL and TG causes Unsustainable increase in HS-HDL.

Atorvastatin reduces plasma cholesterol and lipoprotein concentrations by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and increasing the number of hepatic LDL receptors on the cell surface, which leads to increased capture and catabolism of Xc-LDL.

Atorvastatin reduces the formation of Xc-LDL and the number of LDL particles. Causes a pronounced and persistent increase in the activity of LDL receptors, in combination with favorable qualitative changes in LDL particles. Reduces the level of LDL-LDL in patients with homozygous hereditary hypercholesterolemia resistant to treatment with other lipid-lowering drugs.

Atorvastatin in doses of 10-80 mg reduces the level of total cholesterol by 30-46%, Xc-LDL - by 41-61%, apo-B - by 34-50% and TG - by 14-33%. The results of treatment are similar in patients with heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia and mixed hyperlipidemia, including in patients with non-insulin dependent diabetes mellitus.

In patients with isolated hypertriglyceridemia, atorvastatin reduces the level of total cholesterol, LDL-C, LDL-C, LDL-A, B-A and B and TG and increases the level of LDL-C. In patients with dysbetalipoproteinemia, reduces the level of Xc-Lpp.

In patients with type IIa and IIb hyperlipoproteinemia according to Fredrickson's classification, the mean value of increased HD-C HDL-C levels during treatment with atorvastatin (10-80 mg), compared with baseline, is 5.1-8.7% and is not dose dependent. There is a significant dose-related decrease in the ratio: total cholesterol / Xc-HDL and Xc-LDL / Xc-HDL by 29-44% and 37-55%, respectively.

Atorvastatin at a dose of 80 mg reliably reduces the risk of ischemic complications and death by 16% after a 16-week course, and the risk of repeated hospitalization for angina accompanied by signs of myocardial ischemia is 26%. Atorvastatin causes a reduction in the risk of ischemic complications and death (in patients with myocardial infarction without Q wave and unstable angina, in men and women, patients younger than 65 years of age) in patients with different baseline levels of LDL-LDL.

The decrease in plasma Hc-LDL correlates better with the dose of the drug than with its concentration in the blood plasma.

The therapeutic effect is achieved 2 weeks after the start of therapy, reaches a maximum after 4 weeks and lasts for the entire period of therapy.

Prevention of cardiovascular diseases

In the Anglo-Scandinavian study of cardiac outcomes, lipid-lowering branch (ASCOT-LLA), the effects of atorvastatin on fatal and non-lethal outcomes of IHD found that the effect of atorvastatin therapy at a dose of 10 mg significantly exceeded the effect of placebo, and therefore the decision was made to terminate early research after 3.3 years instead of the expected 5 years.

Atorvastatin significantly reduced the development of the following complications:

There was no significant decrease in total and cardiovascular mortality, although positive trends were observed.

In a joint study of the effects of atorvastatin in patients with type 2 diabetes (CARDS) for fatal and non-lethal outcomes of cardiovascular diseases, it was shown that atorvastatin therapy, regardless of gender, age of the patient, or baseline Xc-LDL, reduced the risk of developing the following cardiovascular complications:

Atherosclerosis

In the study of the reverse development of coronary atherosclerosis with intensive lipid-lowering therapy (REVERSAL) with atorvastatin at a dose of 80 mg in patients with IHD, it was found that the average decrease in the total volume of atheroma (primary efficacy criterion) since the beginning of the study was 0.4%.

Recurrent stroke

The intensive cholesterol-lowering program (SPARCL) found that atorvastatin at a dose of 80 mg / day reduced the risk of recurring fatal or non-fatal stroke in patients who had a stroke or transient ischemic attack without IHD in history by 15% compared with placebo. At the same time, the risk of major cardiovascular complications and revascularization procedures was significantly reduced. A reduction in the risk of cardiovascular disorders during therapy with atorvastatin was observed in all groups except for the one that included patients with primary or recurrent hemorrhagic stroke (7 in the atorvastatin group versus 2 in the placebo group).

Hemorrhagic stroke

In patients receiving atorvastatin therapy at a dose of 80 mg, the incidence of hemorrhagic or ischemic stroke (265 vs. 311) or IHD (123 vs. 204) was less than in the control group.

Secondary prevention of cardiovascular complications

In the treatment of the New Purpose Study (TNT), the effect of atorvastatin at doses of 80 mg / day and 10 mg / day on the risk of developing cardiovascular complications in patients with clinically confirmed coronary artery disease was compared.

Atorvastatin at a dose of 80 mg significantly reduced the development of the following complications:

Pharmacokinetics

Suction

Atorvastatin is rapidly absorbed after ingestion; C_max is achieved in 1-2 hours. The degree of absorption and concentration of atorvastatin in the blood plasma increases in proportion to the dose. The absolute bioavailability of atorvastatin is about 14%, and the systemic bioavailability of the inhibitory activity against HMG-CoA reductase is about 30%. Low systemic bioavailability is due to presystemic metabolism in the gastrointestinal mucosa and / or during the "first pass" through the liver.Food reduces the rate and extent of absorption by about 25% and 9%, respectively (as evidenced by the results of determining C_max and AUC), however, the level of Xc-LDL when taking atorvastatin on an empty stomach and during meals decreases to almost the same extent. Despite the fact that after taking atorvastatin in the evening, his plasma levels are lower (C_max and AUC by about 30%) than after taking in the morning, the decrease in Xc-LDL does not depend on the time of day at which the drug is taken.

Distribution

Medium V_d atorvastatin is about 381 liters. Atorvastatin binding to plasma proteins is at least 98%. The ratio of atorvastatin levels in erythrocytes / blood plasma is about 0.25, i.e. Atorvastatin penetrates poorly into red blood cells.

Metabolism

Atorvastatin is extensively metabolized to form ortho and parahydroxylated derivatives and various beta-oxidation products. In vitro, ortho and parahydroxylated metabolites have an inhibitory effect on HMG-CoA reductase, comparable to that of atorvastatin. Approximately 70% of the inhibitory activity against HMG-CoA reductase is due to the activity of circulating metabolites. The results of in vitro studies suggest that CYP3A4 isoenzyme plays an important role in atorvastatin metabolism. This is confirmed by an increase in the concentration of atorvastatin in human plasma, while taking Erythromycin , which is an inhibitor of this isoenzyme.

In vitro studies have also shown that atorvastatin is a weak inhibitor of the isoenzyme CYP3A4. Atorvastatin had no clinically significant effect on the concentration of terfenadine in plasma, which is metabolized mainly by the CYP3A4 isoenzyme; therefore, a significant effect of atorvastatin on the pharmacokinetics of other substrates of the CYP3A4 isoenzyme is unlikely.

Removal

Atorvastatin and its metabolites are excreted mainly with bile after hepatic and / or extrahepatic metabolism (atorvastatin is not subjected to severe enterohepatic recirculation). T_1/2 is about 14 hours, while the inhibitory effect of the drug against HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites and persists for about 20-30 hours due to their presence. After oral administration, less than 2% of atorvastatin is detected in the urine.

Pharmacokinetics in special clinical situations

Age

Atorvastatin plasma levels in the elderly (≥65 years old) are higher (C_max about 40%, AUC about 30%) than in adult patients of young age. There were no differences in safety, efficacy or achievement of lipid-lowering therapy goals in the elderly compared to the general population.

Studies of the pharmacokinetics of the drug in children were not conducted.

Floor

Atorvastatin plasma concentrations are different in women (C_max about 20% higher, and AUC 10% lower) of those in men.However, there were no clinically significant differences in the effect of the drug on lipid metabolism in men and women.

Renal failure

Impaired renal function does not affect the concentration of atorvastatin in the blood plasma or its effect on lipid metabolism. In this regard, changes in dose in patients with impaired renal function is not required.

Atorvastatin is not excreted during hemodialysis due to intense binding to plasma proteins.

Liver failure

Atorvastatin concentrations increase significantly (C_max and AUC about 16 and 11 times, respectively) in patients with alcoholic cirrhosis of the liver (class B on the Child-Pugh scale).

Indications for use of the drug

- primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia (type IIa according to Fredrickson's classification);

- combined (mixed) hyperlipidemia (types IIa and IIb according to Fredrickson's classification);

- dysbetalipoproteinemia (type III according to Fredrickson's classification) (as a supplement to the diet);

- familial endogenous hypertriglyceridemia (type IV according to Fredrickson's classification), resistant to diet;

- homozygous familial hypercholesterolemia with insufficient efficacy of diet therapy and other non-pharmacological treatment methods;

- primary prevention of cardiovascular complications in patients without clinical signs of coronary artery disease, but having 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, 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

Before starting treatment with Liprimar, you should try to control hypercholesterolemia with diet, exercise and weight loss in obese patients, as well as treatment of the underlying disease.

When prescribing the drug, the patient should be recommended a standard cholesterol-lowering diet, which he must follow during treatment.

The drug is taken orally at any time of the day, regardless of the meal. The dose of the drug varies from 10 mg to 80 mg 1 time / day, the selection of the dose should be carried out taking into account the initial levels of LDL-C, the goal of therapy and the individual effect. The maximum dose is 80 mg 1 time / day.

At the beginning of treatment and / or during the dose increase of Liprimar, it is necessary to control the content of lipids in plasma every 2-4 weeks and adjust the dose accordingly.