Liprimar - instructions for use, analogs, reviews and release forms (tablets 10 mg, 20 mg, 40 mg, 80 mg) of a statin drug for the treatment of hypercholesterolemia and cholesterol reduction in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Lymaris. There are reviews of visitors to the site - consumers of this medicine, as well as opinions of doctors of specialists on the use of statin Lipimar in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Liprimar in the presence of existing structural analogues. Use to treat hypercholesterolemia and reduce cholesterol in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

Lymaris - synthetic hypolipidemic drug. Atorvastatin (the active substance of the drug Lipimar) is a selective competitive inhibitor of HMG-CoA reductase, a key enzyme that converts 3-hydroxy-3-methylglutaryl-CoA into a mevalonate precursor of steroids, including cholesterol.

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

Atorvastatin reduces the concentration of cholesterol and lipoproteins in the blood plasma, inhibiting HMG-CoA reductase and the synthesis of cholesterol in the liver and increasing the number of hepatic LDL receptors on the cell surface, which leads to increased capture and catabolism of LDL-C.

Atorvastatin reduces the production of LDL-C and the number of LDL particles. It causes a pronounced and persistent increase in the activity of LDL receptors, combined with favorable qualitative changes in LDL-particles. Reduces the level of Xc-LDL in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering drugs.

Atorvastatin in doses of 10-80 mg reduces the total cholesterol level by 30-46%, X-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-family forms of hypercholesterolemia and mixed hyperlipidemia, incl. in patients with non-insulin-dependent diabetes mellitus.

In patients with isolated hypertriglyceridemia, atorvastatin reduces total cholesterol, Xc-LDL, Xc-VLDL, apo-B and TG and increases HDL-C level. In patients with disbetalipoproteinemia, the content of intermediate-density lipoprotein cholesterol is lowered.

In patients with hyperlipoproteinemia type 2a and 2b according to Fredrickson classification, the average value of the increase in HDL-C level in the treatment with atorvastatin (10-80 mg), compared with the initial index, is 5.1-8.7% and does not depend on the dose. There is a significant dose-dependent reduction in the ratio: total cholesterol / Xc-HDL and Xc-LDL / XPS-HDL by 29-44% and 37-55%, respectively.

Liprimar in a dose of 80 mg significantly reduces the risk of ischemic complications and the death rate by 16% after a 16-week course, and the risk of re-hospitalization for angina pectoris accompanied by signs of myocardial ischemia is 26%.In patients with different baseline levels of LDL cholesterol, Liprimar reduces the risk of ischemic complications and death (in patients with Q-wave myocardial infarction and unstable angina, men and women, patients younger than 65 years of age).

Reduced plasma levels of Xc-LDL are better correlated with the dose of the drug than with its concentration in the blood plasma.

The therapeutic effect is achieved 2 weeks after the initiation of therapy, reaches a maximum after 4 weeks, and persists throughout the period of therapy.

Composition

Atorvastatin calcium + excipients.

Pharmacokinetics

Liprimar is rapidly absorbed after ingestion. 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%. Low systemic bioavailability is due to presystemic metabolism in the mucosa of the gastrointestinal tract and / or during the "first passage" through the liver. Food reduces the rate and degree of absorption by about 25% and 9%, respectively, but a decrease in X-LDL is similar to that of fasting atorvastatin.Despite the fact that after taking atorvastatin in the evening, its concentration in the plasma is lower than after taking in the morning, the decrease in X-LDL does not depend on the time of day in which the drug is taken. The binding of atorvastatin to plasma proteins is at least 98%. Atorvastatin is largely metabolized with the formation of ortho- and para-hydroxylated derivatives and various beta-oxidation products. Atorvastatin and its metabolites are excreted mainly with bile after hepatic and / or extrahepatic metabolism (atorvastatin does not undergo significant intestinal hepatic recirculation). After ingestion, less than 2% of the dose of atorvastatin is detected in the urine.

Pharmacokinetics in special clinical cases

The concentration of atorvastatin in blood plasma in patients over the age of 65 is higher than in adult patients of a young age. Differences in safety, efficacy, or achievement of the goals of lipid-lowering therapy in elderly patients were not found in comparison with the general population.

Studies of the pharmacokinetics of the drug in children have not been conducted.

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

The concentrations of atorvastatin are significantly increased in patients with alcoholic liver cirrhosis (class B on the Child-Pugh scale).

Indications

• primary hypercholesterolemia (heterozygous familial and non-family hypercholesterolemia (type 2a according to Fredrickson classification);
• combined (mixed) hyperlipidemia (types 2a and 2b according to Fredrickson classification);
• dysetalopoproteinemia (type 3 according to Fredrickson classification) (as a supplement to the diet);
• family endogenous hypertriglyceridemia (type 4 according to Fredrickson classification), resistant to diet;
• homozygous familial hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological methods of treatment;
• Primary prophylaxis of cardiovascular complications in patients without clinical signs of IHD, but having several risk factors for its development - age over 55, nicotine dependence, arterial hypertension, diabetes mellitus, low HDL-C concentrations in blood plasma, genetic predisposition, h. against dyslipidemia;
• secondary prevention of cardiovascular complications in patients with ischemic heart disease in order to reduce the overall mortality rate, myocardial infarction,stroke, repeated hospitalization for angina pectoris and the need for revascularization.

Forms of release

Tablets coated with 10 mg, 20 mg, 40 mg, 80 mg.

Instructions for use and dosing regimen

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

When appointing the drug, the patient should recommend a standard hypocholesterolemic diet, which he must observe during treatment.

The drug is taken orally at any time of the day, regardless of food intake.

The dose of the drug varies from 10 mg to 80 mg once a day, the dose should be selected taking into account the initial content of LDL-C, the purpose of therapy and the individual effect. The maximum dose is 80 mg once a day.

At the beginning of treatment and / or during an increase in the dose of Lipimar, the level of lipid in the plasma should be controlled every 2-4 weeks and the dose adjusted accordingly.

With primary hypercholesterolemia and combined (mixed) hyperlipidemia, for most patients the Liprimar dose is 10 mg once a day.Therapeutic effect manifests itself within 2 weeks and usually reaches a maximum within 4 weeks. With prolonged treatment, the effect persists.

With homozygous familial hypercholesterolemia, the drug is prescribed at a dose of 80 mg once a day (a decrease in the level of LDL-C in 18-45%).

In case of liver failure, the dose of Lipimar must be reduced under the constant control of the activity of ACT and ALT.

Violation of the kidney function does not affect the concentration of atorvastatin in the blood plasma or the degree of decrease in the content of LDL-C during Liprimar, so no dose adjustment is required.

With the use of the drug in elderly patients, differences in efficacy and safety are not found in comparison with the general population, and dose adjustment is not required.

If you need to share with cyclosporine, the dose of Lipimar should not exceed 10 mg.

Side effect

• insomnia;
• headache;
• asthenic syndrome;
• nausea, vomiting;
• diarrhea, constipation;
• abdominal pain;
• dyspepsia;
• flatulence;
• myalgia;
• malaise;
• dizziness;
• amnesia;
• peripheral neuropathy;
• hypoesthesia;
• anorexia;
• hepatitis;
• pancreatitis;
• backache;
• muscle cramps;
• myositis;
• rhabdomyolysis;
• hives;
• itching;
• skin rash;
• anaphylactic reactions;
• bullous rash;
• multi-form exudative erythema (including Stevens-Johnson syndrome);
• toxic epidermal necrolysis (Lyell's syndrome);
• hypoglycemia;
• hyperglycemia;
• thrombocytopenia;
• impotence;
• peripheral edema;
• increase in body weight;
• chest pain;
• secondary renal failure;
• alopecia;
• noise in ears;
• increased fatigue.

Contraindications

• active liver disease or an increase in serum transaminase activity (more than 3 times as compared with IGN) of an unknown genesis;
• age under 18 years (not enough clinical data on efficacy and safety for this age group);
• hypersensitivity to the components of the drug.

Application in pregnancy and lactation

Liprimar is contraindicated in pregnancy and lactation (breastfeeding).

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.

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

Use in children

Contraindicated in children and adolescents under 18 years (not enough clinical data on efficacy and safety for this age group).

Application in elderly patients

With the use of the drug in elderly patients, differences in efficacy and safety are not found in comparison with the general population, and dose adjustment is not required.

special instructions

Action on the liver

As with the use of other lipid-lowering drugs of the same class, after treatment with Liprimar, a moderate (more than 3-fold compared with HHV) increased serum activity of AST and ALT. A steady increase in the serum level of hepatic transaminases (more than 3-fold compared with IGN) was observed in 0.7% of patients who received Liprimar in clinical studies. The frequency of such changes when using the drug at doses of 10 mg, 20 mg, 40 mg and 80 mg was 0.2%, 0.2%, 0.6% and 2.3%, respectively.Increased activity of hepatic transaminases was usually not accompanied by jaundice or other clinical manifestations. When the dose of Lipimar was reduced, the activity of hepatic transaminases returned to the initial level temporarily or completely. Most patients continued to receive Liprimar in a reduced dose without any clinical consequences.

Before the beginning, after 6 weeks and 12 weeks after the beginning of the use of the drug or after increasing the dose, as well as during the entire course of treatment, it is necessary to monitor the indicators of liver function. The liver function should also be investigated when there are clinical signs of liver damage. In the case of increased activity of hepatic transaminases, their activity should be monitored until it is normalized. If the increase in the activity of AST or ALT more than 3 times compared with VGN persists, it is recommended to reduce the dose or cancel the drug Lipimar.

Action on skeletal muscles

Myalgia was observed in patients receiving Liprimar. The diagnosis of myopathy (pain and weakness in muscles in combination with an increase in CKK activity more than 10 times compared to IGN) should be assumed inpatients with diffuse myalgia, muscle soreness or weakness, and / or a marked increase in CKK activity. Liprimar therapy should be discontinued if there is a marked increase in CK activity, with confirmed or suspected myopathy. The risk of myopathy in the treatment of other drugs in this class are increased while the use of cyclosporine, fibrates, erythromycin, nicotinic acid as lipid-lowering doses (more than 1 g) or antifungal drugs (azole derivatives). Many of these drugs inhibit the metabolism mediated by the CYP3A4 isoenzyme and / or drug transport. It is known that the isoenzyme cytochrome CYP3A4 - primary liver isoenzyme involved in the biotransformation of atorvastatin. Assigning Lipitor in combination with fibrates, erythromycin, immunosuppressants, antifungal agents (azole derivatives), nicotinic acid or a lipid-lowering doses should carefully weigh the potential benefits and risks of treatment possible. Patients should be monitored regularly to identify pain or weakness in the muscles, especially during the first months of treatment and during periods of increasing the dose of any drug.If combination therapy is required, the use of these drugs in lower initial and maintenance doses should be considered. In such situations, it may be recommended to periodically determine the activity of CK, although such monitoring does not prevent the development of severe myopathy.

When using the drug Lipimar, as well as other statins, rare cases of rhabdomyolysis with acute renal failure due to myoglobinuria are described. When symptoms of possible myopathy or the presence of a risk factor for developing renal failure against rhabdomyolysis (for example, severe acute infection, arterial hypotension, extensive surgery, trauma, metabolic, endocrine and electrolyte disturbances and uncontrolled convulsions), Liprimar therapy should be temporarily discontinued or completely abolished .

Patients should be warned that they should immediately consult a doctor if unexplained pain or weakness in the muscles occurs, especially if they are accompanied by a malaise or fever.

Impact on the ability to drive vehicles and manage mechanisms

Data on the effect of atorvastatin on the ability to drive vehicles and engage in potentially dangerous activities that require increased concentration and speed of psychomotor reactions are not available.

Drug Interactions

The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases with simultaneous use of cyclosporine, fibrates, erythromycin, clarithromycin, antifungal preparations of azole derivatives and nicotinic acid in lipid-lowering doses.

Inhibitors of the isoenzyme CYP3A4

Since atorvastatin is metabolized by the CYP3A4 isoenzyme, the combined use of Liprimar with inhibitors of this isoenzyme can lead to an increase in the concentration of atorvastatin in the blood plasma. The degree of interaction and potentiation effect is determined by the variability of the effect on the isoenzyme CYP3A4.

Inhibitors of transport protein OATP1B1

Atorvastatin and its metabolites are substrates of the transport protein OATP1B1. Inhibitors of OATP1B1 (eg, cyclosporin) may increase the bioavailability of atorvastatin. Thus, the combined use of atorvastatin in a dose of 10 mg and cyclosporine at a dose of 5.2 mg / kg per day leads to an increase in the concentration of atorvastatin in blood plasma by 7.7 times.

Erythromycin / clarithromycin

With the simultaneous use of Liprimar and Erythromycin (500 mg 4 times a day) or Clarithromycin (500 mg twice daily) that inhibit CYP3A4, an increase in the concentration of atorvastatin in the blood plasma was observed (with simultaneous application of ри of atorvastatin with erythromycin, Cmax is increased by 40% ).

Inhibitors of proteases

Simultaneous use of Lipimar with protease inhibitors, known as inhibitors of CYP3A4, is accompanied by an increase in the concentration of atorvastatin in the blood plasma.

Diltiazem

The combined use of Lipimar in a dose of 40 mg with diltiazem in a dose of 240 mg leads to an increase in the concentration of atorvastatin in the blood plasma.

Cimetidine

Clinically significant interaction of Liprimar with cimetidine was not detected.

Itraconazole

Simultaneous use of Lipimar in doses of 20 mg to 40 mg and Itraconazole at a dose of 200 mg led to an increase in the value of AUC atorvastatin.

Grapefruit juice

Since grapefruit juice contains one or more components that inhibit the isoenzyme CYP3A4, its excessive intake (more than 1.2 liters per day) can cause an increase in the concentration of atorvastatin in the blood plasma.

Inductors of the cytochrome isoenzyme CYP3A4

The combined use of Liprimar with inducers of the cytochrome CYP3A4 isoenzyme (eg, efavirenz or rifampicin) can lead to a decrease in the concentration of atorvastatin in the blood plasma. Due to the dual mechanism of interaction with rifampicin (inducer of cytochrome CYP3A4 isoenzyme and inhibitor of hepatocyte transport protein OATP1B1) simultaneous use of atorvastatin and rifampicin is recommended, since delayed administration of atorvastatin after taking rifampicin leads to a significant decrease in the concentration of atorvastatin in the blood plasma.

Antacids

With the simultaneous administration of Liprimar and a suspension containing magnesium and aluminum hydroxides, the concentration of atorvastatin in the plasma decreased by approximately 35%, but the degree of decrease in the level of LDL-C was not changed.

Fenazone

With simultaneous application of Liprimar does not affect the pharmacokinetics of phenazone, therefore interaction with other drugs metabolized by the same isoenzymes of cytochrome is not expected.

Kolestypol

With simultaneous application of colestipol, the concentration of atorvastatin in plasma decreased by about 25%.However, the hypolipidemic effect of the combination of atorvastatin and colestipol was superior to that of each drug individually.

Digoxin

With repeated administration of Digoxin and Liprimar in a dose of 10 mg, the equilibrium concentrations of digoxin in the blood plasma did not change. However, when using digoxin in combination with Liprimar at a dose of 80 mg per day, the digoxin concentration increased by about 20%. Patients receiving digoxin in combination with Liprimar require clinical control.

Azithromycin

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

Oral contraceptives

When Liprimar and an oral contraceptive containing norethisterone and ethinylestradiol were used concomitantly, there was a significant increase in the AUC of norethisterone and ethinylestradiol by approximately 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving Liprimar.

Terfenadine

Liprimar, when used concurrently, did not have a clinically significant effect on the pharmacokinetics of terfenadine.

Warfarin

Symptoms of clinically significant interaction of atorvastatin with Warfarin were not detected.

Amlodipine

With the simultaneous administration of Lipimar in a dose of 80 mg and Amlodipine at a dose of 10 mg, the pharmacokinetics of atorvastatin did not change in the equilibrium state.

Other concomitant therapy

In clinical trials, Liprimar was used in combination with antihypertensive agents and estrogens, which were prescribed as substitution therapy; Symptoms of clinically significant undesirable interaction were not noted. Studies of interaction with specific drugs have not been conducted.

Analogues of Lipimar drug

Structural analogs for the active substance:

• Anistat;
• Atokord;
• Atomax;
• Ator;
• Atorvastatin;
• Atorvox;
• Atoris;
• The Vasator;
• Lipon;
• Lipofford;
• Liptonorm;
• Novostat;
• Torvazine;
• Torvacard;
• Torvalip;
• Torvas;
• Tulip.

Analogues for the pharmacological group (statins):

• Akorta;
• Aktalipid;
• Apexstatin;
• Atherostat;
• Atokord;
• Atorvastatin;
• Atorvox;
• Atoris;
• Vazilip;
• Zocor;
• Zorstat;
• Cardiostatin;
• The Cross;
• Leskol;
• Lipobay;
• Lipostat;
• Lovacor;
• Lovastatin;
• Lovasterol;
• Mevakor;
• Medostatin;
• Mertenil;
• Novostat;
• Ovenkor;
• Pravastatin;
• Rovacor;
• Rosart;
• Rosuvastatin;
• Rosewood;
• Rosulip;
• Roxer;
• Simvard;
• Simvakol;
• Simvastatin;
• Simvastol;
• Simgal;
• Simlo;
• Sinquard;
• Tevastor;
• Torvazine;
• Torvacard;
• Torvalip;
• Torvas;
• Tulip;
• Holvasim;
• Holletar.

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