Liprimar pills 40mg №30

Coated tablets

Composition

In 1 tablet, film coated, contains:

- Active substances
- Atorvastatin (in the form of Calcium salt) 40 mg.

- Calcium carbonate excipients, microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, polysorbate-80, hyprolosis, Magnesium stearate.

- Composition of the shell Opadray white YS-1-7040 (contains hypromellose, polyethylene glycol, titanium dioxide, talc), simethicone emulsion (contains simethicone, stearic emulsifier, sorbic acid, water), candelica wax.

Packing

In the blister of 10 tablets. In packing 3 blisters.

Mechanism of action

Liprimar-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; synthetic lipid-lowering agent.

In patients with homozygous and heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia and mixed dyslipidemia.very low density lipoproteins (Xc-VLDL) and triglycerides (TG), causes an unstable increase in high-density lipoprotein cholesterol (Xc-HDL).

Reduces the concentration of cholesterol and lipoproteins in the blood plasma, 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 uptake and catabolism of Xc-LDL.

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 cholesterol-LDL in patients with homozygous hereditary hypercholesterolemia, resistant to treatment with other lipid-lowering drugs.

Liprimar at a dose of 10-80 mg reduces the level of total cholesterol by 30-46%, Xc-LDL by 41-61%, apolipoprotein B by 34-50% and triglyceride 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, Liprimar lowers total cholesterol, Xc-LDL, Xc-VLDL, apo-B, and TG and increases the level of Xc-HDL. In patients with dysbetalipoproteinemia, lowers lipoprotein cholesterol intermediate density.

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 Liprimar (10-80 mg), compared with baseline, is 5.1-8.7% and is not dose dependent.There is a significant dose-dependent decrease in the ratio: total cholesterol / Xc-HDL and Xc-LDL / Xc-HDL by 29-44% and 37-55%, respectively.

Liprimar 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 re-hospitalization for angina, accompanied by signs of myocardial ischemia, by 26%. In patients with different baseline levels of Xc-LDL, Liprimar causes a reduction in the risk of ischemic complications and death (in patients with myocardial infarction without Q wave and unstable angina, men and women, patients younger than 65 years of age).

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

- Prevention of cardiovascular diseases In an Anglo-Scandinavian study of cardiac outcomes, a lipid-lowering branch (ASCOT-LLA), the effect of atorvastatin on fatal and non-lethal outcomes of coronary heart disease (cardiovascular mortality, hospitalization for unstable angina) was evaluated in patients with cardiovascular mortality, hospitalization for unstable angina, was evaluated in patients with cardiovascular mortality, hospitalization for unstable angina) was evaluated in patients with cardiovascular mortality, hospitalization for unstable angina) was assessed in patients with cardiovascular mortality, hospitalization for unstable angina) was assessed in patients with cardiovascular mortality, hospitalization for unstable angina) was evaluated in patients with cardiovascular mortality, hospitalization for unstable angina) was assessed in patients with cardiovascular mortality, hospitalization for unstable angina) was evaluated in patients with cardiovascular mortality, hospitalization for unstable angina) was evaluated in patients with heart failure, cardiovascular mortality, hospitalization for unstable angina) were evaluated in patients with cardiovascular mortality, hospitalization for unstable angina). 80 years (63 on average) without a myocardial infarction (MI) in the anamnesis and with an initial level of total cholesterol of more than 6.5 mmol / l (251 mg / dl). All patients also had at least 3 cardiovascular risk factors: male gender, age over 55 years old, smoking, diabetes mellitus, ischemic heart disease in a first-degree relative, the ratio of total cholesterol to HD-C HDL levels of more than 6, peripheral disease vessels, left ventricular hypertrophy, history of cerebral circulation, specific ECG changes, proteinuria and albuminuria.In the study, patients with arterial hypertension simultaneously with prescribed antihypertensive therapy (target BP less than 140/90 mmHg for all patients and less than 130/80 for patients with diabetes mellitus) were administered atorvastatin in a dose of 10 mg / day or placebo. Due to the fact that according to the interim analysis, the effect of the drug therapy significantly exceeded the effect of using placebo, it was decided to terminate the study early after 3.3 years instead of the expected 5 years. Atorvastin significantly reduced the risk of the following complications: Complications Reduced risk Coronary complications (coronary artery disease and fatal MI) 36% General cardiovascular complications and revascularization procedures 20% General coronary complications 29% Stroke (fatal and non-fatal) 26% Significant reduction in indicators there was no overall mortality and mortality from cardiovascular causes, although positive trends were observed.

- Diabetes mellitus In a joint study of the effect of atorvastatin on fatal and non-fatal outcomes of cardiovascular diseases in type 2 diabetes mellitus (CARDS), it was shown that atorvastatin therapy reduced the risk of developing the following cardiovascular complications regardless of gender, age of the patient or baseline Xc- LDL: Complications Reducing the risk of Major cardiovascular complications (fatal and nonfatal acute myocardial infarction (MI), hidden MI, death due to exacerbation of coronary artery disease,unstable angina, coronary artery bypass surgery, subcutaneous transluminal coronary angioplasty, revascularization, stroke) 37% Myocardial infarction (fatal and nonfatal acute myocardial infarction, latent MI) 42% Stroke (fatal and nonfatal) 48%

- Atherosclerosis In the study of the reverse development of coronary atherosclerosis with intensive lipid-lowering therapy (REVERSAL) with atorvastatin 80 mg in patients with coronary artery disease, 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. In an intensive cholesterol-lowering program (SPARCL), it was found that atorvastatin at a dose of 80 mg per day reduced the risk of recurring fatal or non-fatal stroke in patients who had a stroke or transient ischemic attack (TIA) without a history of CHD 15% compared to 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 in therapy with atorvastatin was noted 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 who received 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 interpretation 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 heart disease was compared. Atorvastatin at a dose of 80 mg significantly reduced the development of the following complications: Complications Atorvastatin 80 mg Primary endpoint The first important cardiovascular complication (coronary heart disease and fatal myocardial infarction) 8.7% nonfatal IM, non-related 4.9% Stroke ( fatal and nonfatal) 2.3% Secondary end point First hospitalization for congestive heart failure 2.4% First coronary artery bypass or other revascularization procedures 13.4% First documented angina pectoris 10.3%

- Primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia (Frederickson type IIa).
- Combined (mixed) hyperlipidemia (Frederickson type IIa and IIb types).
- Dysbetalipoproteinemia (type III according to Frederickson) (as a supplement to the diet).
- Familial endogenous hypertriglyceridemia (type IV according to Frederickson), resistant to diet.
ELIBRARY.RU. Homozygous familial hypercholesterolemia with insufficient effectiveness 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.
- Nicotine addiction.
- Arterial hypertension .
- Diabetes.
- Low concentrations of Xc-HDL in plasma.
- Genetic predisposition, incl. against dyslipidemia.

- In patients with coronary artery disease with the aim of reducing the total mortality rate.
- Myocardial infarction.
- Stroke.
- Re-hospitalization for angina and the need for revascularization.

- Hypersensitivity to any of the components of the drug.
- Active liver disease or increased serum transaminase activity (AST, ALT) (more than 3 times compared with the upper limit of normal) of unclear genesis.
- Women of reproductive age who do not use adequate methods of contraception.
- Pregnancy.
- Lactation (breastfeeding).
- Age up to 18 years (not enough clinical data on the efficacy and safety of the drug in this age group).

Carefully:

- Alcohol abuse.
- Liver disease (in history).

Liprimar is contraindicated in pregnancy.

Women of reproductive age during treatment should use adequate methods of contraception. Liprimar can be prescribed to women of reproductive age only if the probability of pregnancy is very low and the patient is informed of the possible risk to the fetus during treatment.

Liprimar is contraindicated during lactation.

It is not known whether atorvastatin is excreted in breast milk. If necessary, the appointment of the drug during lactation, breastfeeding should be stopped to avoid the risk of adverse events in infants.

Inside Take at any time of the day, regardless of the meal.

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 advised to recommend a standard cholesterol-lowering diet, which he must follow during treatment.

The dose of the drug varies from 10 to 80 mg 1 time per day and is titrated based on the initial content of Xc-LDL, the goal of therapy and the individual effect.

The maximum daily dose for a single dose is 80 mg.

At the beginning of treatment and / or during a dose increase of Liprimar, it is necessary to monitor plasma lipid levels every 2-4 weeks and adjust the dose accordingly.

- With primary hypercholesterolemia and combined (mixed) hyperlipidemia. For most patients - 10 mg 1 time / day. The therapeutic effect occurs within 2 weeks and usually reaches a maximum within 4 weeks. With long-term treatment, the effect is preserved.

- When homozygous familial hypercholesterolemia. The drug is prescribed at a dose of 80 mg 1 time / day (in most cases, therapy led to a decrease in the level of Xc-LDL by 18-45%).

- In case of insufficient liver function, the Liprimar dose should be reduced, with constant monitoring of the activity of “liver” transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT).

- In case of insufficiency of the kidney function Impaired renal function does not affect the plasma atorvastatin level or the degree of decrease in the LDL-C content when using Liprimar, therefore, changing the dose of the drug is not required.

- In elderly patients There were no differences in safety, efficacy, or achievement of lipid-lowering therapy goals compared to the general population.

- Use in combination with other drugs. If necessary, joint use with cyclosporine dose of the drug should not exceed 10 mg.

In determining the goal of treatment, you can use the following recommendations:

- A. Recommendations of the National Cholesterol Education Program NCEP, USA. Category of risk Target content of Hc-LDL (mg / dl) Content of Hc-LDL, which recommends a change in lifestyle (mg / dl) summer risk> 20%) <100? 100 ? 130 (100-129 pharmacotherapy is possible) * More than 2 risk factors (10-year risk? 20%) <130? 130 10-year risk of 10-20%:? 130 10-year risk <10% :? 160 0-1 risk factor ** <160? 160? 190 (160-189: prescribe a drug that reduces the content of Xc-LDL) * Some experts recommend the use of lipid-lowering drugs cholesterol - LDL, if the lifestyle change does not reduce its content to less than 100 mg / dl.Others prefer drugs that have a predominant effect on triglycerides and HDL cholesterol, such as nicotinic acid and fibrates. The physician may also postpone pharmacotherapy in this subgroup. ** In the absence of risk factors or the presence of only one risk factor in almost all people, the 10-year risk is less than 10%, so its assessment is not required. If the target LDL cholesterol is reached, and the triglyceride content is kept at 200 mg / dL, then the secondary goal of therapy is to reduce cholesterol, excluding LDL-C at 30 mg / dL in each risk category.

- B. Objectives of hypolipidemic therapy of the European Society of Atherosclerosis In patients with a confirmed diagnosis of coronary artery disease and other patients with a high risk of ischemic complications, the goal of treatment is to reduce the level of Xc-LDL less than 3 mmol / l (or less than 115 mg / dl) and total cholesterol less than 5 mmol / L (or less than 190 mg / dL).

For ease of use it is also possible to use:

- Effect on the liver As with the use of other lipid-lowering drugs of this class, after treatment with Liprimar, a moderate (more than 3 times compared with the upper limit of the norm) increase in the activity of “liver” transaminases ACT and ALT was noted. A persistent increase in the serum content of liver transaminases (more than 3 times as compared with the upper limit of the norm) was observed in 0.7% of patients receiving Liprimar.The frequency of such changes when using the drug in doses of 10 mg. 20 mg. 40 mg and 80 mg were 0.2%, 0.2%, 0.6% and 2.3%, respectively. An increase in liver transaminase activity is usually not accompanied by jaundice or other clinical manifestations. With a decrease in the dose of the drug, temporary or complete cancellation of the drug, the activity of “liver” transaminases returned to the initial level. Most patients continued to take the drug in a reduced dose without any clinical consequences. Before starting therapy, after 6 weeks and 12 weeks after starting Liprimar or after increasing the dose, as well as during the entire course of treatment, it is necessary to monitor indicators of liver function. Liver function should also be investigated when clinical signs of liver damage appear. In the case of increased levels of "liver" transaminases, their activity should be monitored until it is normalized. If the increase in the activity of ACT or ALT is more than 3 times higher than the upper limit of the norm, a dose reduction or drug withdrawal is recommended. Liprimar should be used with caution in patients who consume significant amounts of alcohol and / or have a history of liver disease. Active liver disease or constantly elevated levels of “liver” transaminases of blood plasma of unknown origin are a contraindication to the use of the drug Liprimar.

- Effect on skeletal muscles Patients who received the drug Liprimar, had myalgia. The diagnosis of myopathy (muscle pain or muscle weakness in combination with an increase in CPK activity of more than 10 times compared with the upper limit of normal) should be assumed in patients with diffuse myalgia, muscle soreness or weakness and / or a pronounced increase in CPK activity. Therapy with Liprimar should be stopped in case of a pronounced increase in the activity of CPK, in the presence of a confirmed myopathy or presumptive. The risk of myopathy in the treatment of other drugs of this class increased with the simultaneous use of cyclosporine, fibrates, Erythromycin, nicotinic acid in lipid-lowering doses (more than 1 g) or azole antifungal agents. Many of these drugs inhibit metabolism mediated by the cytochrome CYP3A4 isoenzyme, and / or drug transport. Cytochrome CYP3A4 isoenzyme is known to be the main liver isoenzyme involved in atorvastatin biotransformation. When prescribing the drug in combination with fibrates, erythromycin, immunosuppressants, azole antifungal agents, or lipid-lowering doses of nicotinic acid, the physician must carefully weigh the expected benefit of the treatment and the possible risk. Patients should be regularly monitored to identify pain or weakness in the muscles, especially during the first months of therapy and during the period of increasing the dose of any of these funds.If necessary, combination therapy should consider the possibility of using lower initial and maintenance doses of the above funds. In such situations, periodic monitoring of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy. When using the drug Liprimar as well as other statins, rare cases of rhabdomyolysis with acute renal failure caused by myoglobinuria are described. If symptoms of possible myopathy appear or there is a risk factor for the development of renal failure due to rhabdomyolysis (for example, severe acute infection, arterial hypotension, extensive surgical intervention, trauma, metabolic, endocrine and electrolyte disturbances and uncontrolled seizures), Liprimar should be temporarily stopped or completely canceled . Attention! Patients should be warned that they should immediately see a doctor if they develop unexplained pains or muscle weakness, especially if they are accompanied by indisposition or fever.

- There is no impact on the ability to drive motor vehicles and control the mechanisms of data on the effect of atorvastatin on the ability to drive a car and engage in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases with the simultaneous use of cyclosporine, fibrates, erythromycin, Clarithromycin, antifungal agents derived from azole, and nicotinic acid in lipid-lowering doses.

- Inhibitors of cytochrome CYP3A4 isoenzyme Since atorvastatin is metabolized by cytochrome CYP3A4 isoenzyme, the combined use of atorvastatin with cytochrome isoenzyme CYP3A4 inhibitors may lead to an increase in atorvastatin plasma levels. The degree of interaction and the effect of potentiation are determined by the variability of exposure to the cytochrome CYP3A4 isoenzyme.
- Inhibitors of the transport protein OAT1B1 Atorvastatin and its metabolites are substrates of the transport protein OATP1B1. OATR1B1 inhibitors (for example, cyclosporin) can increase the bioavailability of atorvastatin. Thus, the combined use of atorvastatin at a dose of 10 mg and cyclosporine at a dose of 5.2 mg / kg / day leads to an increase in the concentration of atorvastatin in the blood plasma by 7.7 times.

- Erythromycin / clarithromycin With simultaneous use of atorvastatin and erythromycin (500 mg 4 times a day) or clarithromycin (500 mg 2 times a day), which inhibit the cytochrome CYP3A4 isoenzyme, an increase in atorvastatin plasma levels was observed.

- Protease inhibitors Simultaneous use of atorvastatin with protease inhibitors, known as inhibitors of cytochrome CYP3A4 isoenzyme, is accompanied by an increase in plasma atorvastatin concentration (with simultaneous use with erythromycin C max, atorvastatin is increased by 40%).

- Diltiazem The combined use of atorvastatin at a dose of 40 mg with diltiazem at a dose of 240 mg leads to an increase in plasma concentration of atorvastatin.

- Cimetidine Clinically significant interaction of atorvastatin with cimetidine was not detected.

- Itraconazole The simultaneous use of atorvastatin in doses from 20 mg to 40 mg and itraconazole in a dose of 200 mg led to an increase in the AUC value of atorvastatin.

- Grapefruit juice Because grapefruit juice contains one or more components that inhibit the cytochrome CYP3A4 isoenzyme, its excessive consumption (more than 1.2 liters per day) can cause an increase in plasma atorvastatin concentration.

- Inductors of cytochrome CYP3A4 isoenzyme The combined use of atorvastatin with inductors of the cytochrome CYP3A4 isoenzyme (for example, efavirenz or rifampicin) can lead to a decrease in plasma concentration of atorvastatin. Due to the dual mechanism of interaction with rifampicin (an inducer of cytochrome CYP3A4 isoenzyme and an inhibitor of hepatocyte transport protein OATP1B1), simultaneous use of atorvastatin and rifampicin is recommended, since delayed atorvastatin intake after taking rifampicin leads to a significant decrease in atorvastatin concentration in the blood plasma.
- Antacids Simultaneous intake of a suspension containing magnesium hydroxide and aluminum hydroxide, reduced the concentration of atorvastatin in the blood plasma by about 35%, however, the degree of reduction of Xc-LDL did not change.

- Phenazone Atorvastatin does not affect the pharmacokinetics of phenazone, therefore, interaction with other drugs metabolized by the same cytochrome isoenzymes is not expected.

- Colestipol With simultaneous use of colestipol, the concentration of atorvastatin in the blood plasma decreased by approximately 25%; however, the lipid-lowering effect of the combination of atorvastatin and colestipol was superior to that of each drug separately.

- Digoxin When repeated administration of digoxin and atorvastatin at a dose of 10 mg, the equilibrium concentration of digoxin in the blood plasma did not change. However, when using digoxin in combination with atorvastatin at a dose of 80 mg / day, the concentration of digoxin increased by about 20%. Patients receiving digoxin in combination with atorvastatin require appropriate monitoring.

- Azithromycin With simultaneous use of atorvastatin in a dose of 10 mg 1 time per day and azithromycin in a dose of 500 mg 1 time per day, the concentration of atorvastatin in the blood plasma did not change.

- Oral contraceptives With simultaneous use of atorvastatin and an oral contraceptive containing norethisterone and ethinyl estradiol, there was a significant increase in the AUC of norethisterone and ethinyl estradiol by about 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman taking atorvastatin.

- Terfenadine With simultaneous use of atorvastatin and terfenadine, no clinically significant changes in the pharmacokinetics of terrenadine were detected.

- Warfarin Signs of clinically significant interaction of atorvastatin with warfarin not detected.

- Amlodipine With simultaneous use of atorvastatin at a dose of 80% of amlodipine at a dose of GO mg, the pharmacokinetics of atorvastatin did not change in the equilibrium state.

- Other concomitant therapy. In clinical studies, atorvastatin was used in combination with antihypertensive drugs and estrogens as part of replacement therapy; signs of clinically significant undesirable interactions were noted; Research on the interaction with specific drugs was not conducted.

- Symptoms: increased side effects.
- Treatment: there is no specific antidote for the treatment of overdose with Liprimar. In case of overdose, symptomatic treatment should be carried out as needed. Since the drug is actively associated with plasma proteins, hemodialysis is ineffective.

- Store at a temperature not higher than 25 ° С.
- Keep out of reach of children.
- Do not use after expiration date.

3 years.