Description
Latin name
Liprimar
release tablets coated tablets coated
Packing
30 pcs
Pharmacological action
Liprimar – lipid-lowering drug. Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, a key enzyme that converts 3-hydroxy-3-methylglutaryl-CoA to mevalonic acid, a precursor to steroids, including cholesterol.
In patients with homozygous and heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia and mixed dyslipidemia, Liprimar lowers total cholesterol (Ch), low-density lipoprotein (Ch-LDL) cholesterol and very low-density apolipoprotein B (LON), as well as ) and triglycerides, causes an unstable increase in high-density lipoprotein cholesterol (HDL-C).
In the liver, triglycerides and cholesterol are incorporated into very low density lipoproteins (VLDL), enter the plasma, and are transported to peripheral tissues. Low density lipoproteins (LDL) are formed from VLDL, which are catabolized by interaction with high-affinity LDL receptors.
Like LDL, cholesterol-rich and triglyceride-rich lipoproteins (VLDL, intermediate density lipoproteins and chylomicron residues) can also contribute to the progression of atherosclerosis. An increase in plasma triglycerides is often combined with a decrease in HDL-C and the appearance of small LDL particles, as well as other non-lipid metabolic risk factors for coronary heart disease. In this regard, the independent role of hypertriglyceridemia as an independent risk factor for coronary heart disease has not been convincingly proven. An independent effect of increasing HDL or lowering triglycerides on the risk of coronary or cardiovascular complications and death from these causes has also not been established.
Liprimar reduces plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and increasing the number of hepatic LDL receptors on the cell surface, leading to increased uptake 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, in combination with favorable qualitative changes in LDL particles. Reduces the level of LDL-C in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering drugs.
Atorvastatin at a dose of 10-80 mg reduces total cholesterol by 30-46%, LDL-C by 41-61%, apolipoprotein B by 34-50% and triglycerides by 14-33%. The treatment results 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 lowers total cholesterol, Chs-LDL, Chs-VLDL, apolipoprotein B, triglycerides and Chs-not HDL-C and increases the level of Chs-HDL. In patients with dysbetalipoproteinemia, intermediate-density lipoprotein cholesterol levels are reduced.
In patients with type IIa and IIb hyperlipoproteinemia according to the Fredrickson classification, the average value of increasing HDL-C during treatment with atorvastatin (10-80 mg), compared with the initial value, is 5.1-8.7% and does not depend on the dose. There is a significant dose-dependent decrease in the ratio: total cholesterol / Chs-HDL and Chs-LDL / Chs-HDL by 29-44% and 37-55%, respectively.
Atorvastatin at a dose of 80 mg significantly reduces the risk of ischemic complications and death 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-C, atorvastatin causes a comparable decrease in the risk of ischemic complications and death (in patients with myocardial infarction without Q wave and unstable angina, men and women, patients under the age of 65 years).
Liprimar (10 mg / day) significantly reduces the incidence of the following complications: coronary heart disease (fatal + heart attack without fatal outcome) – by 36%, cardiovascular disease and the use of revascularization procedures – by 20%, coronary heart disease – by 29%, stroke (including with a fatal outcome) – by 26%.
There was no significant reduction in overall mortality and mortality from cardiovascular complications with Liprimar, but there was a downward trend in mortality.
Indications of
in combination with a diet to lower elevated total cholesterol, HDL-C, apolipoprotein B and triglycerides and increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and non-familial hypercholemia of cholesterol II) and cholesterol-mixed cholesterol classification), in which diet therapy does not give an adequate effect of
in combination with a diet for the treatment of patients with elevated serum triglycerides (type IV according to the classification of Fredrickson) and patients with sbetalipoproteinemiey (type III Fredrickson classification) in which diet therapy does not provide an adequate effect of
to reduce total cholesterol and LDL-C in patients with homozygous familial hypercholesterolemia with insufficient efficacy of diet therapy and other non-pharmacological treatments for
to reduce the risk of lethal outcomes of IHD and the risk of myocardial infarction, angina pectoris and stroke reduce the need for revascularization procedures in patients with cardiovascular diseases and / or dyslipidemia, as well as if these diseases were not detected us, but there are at least three risk factors for coronary heart disease, such as age over 55, smoking, hypertension, low blood concentrations of LDL-HDL plasma cases of coronary heart disease early development relatives.
Contraindications
active liver disease or an increase in the serum activity of transaminases (more than 3 times higher than the normal limit) of unclear genesis
of a woman of reproductive age who does not use adequate methods of contraception
pregnancy
lactation (breastfeeding component) the drug
in children and adolescents under the age of 18 years, the effectiveness and safety of liprimar have not been established.
Caution should be used in patients who abuse alcohol and / or have a liver disease (history).
Use during pregnancy and lactation
Liprimar ® is contraindicated in pregnancy.
Women of reproductive age should use adequate contraceptive methods during treatment. Liprimar ® can be prescribed to women of reproductive age only if if the probability of pregnancy is very low and the patient is informed about the possible risk of treatment for the fetus.
Liprimar ® is contraindicated during lactation. It is not known whether atorvastatin is excreted in breast milk. If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped to avoid the risk of adverse events in infants.
Composition
1 tablet contains:
Active ingredient: atorvastatin (in the form of calcium salt) 10 mg
Excipients: calcium carbonate, microcrystalline cellulose, lactose monohydrate, sodium carboxymethyl cellulose, Polysorbate 80, White hydroxide, Hydroxypropylate, White hydroxide, Op hydroxide -7040, simethicone emulsion, wax powder.
Dosage and administration of
Before starting treatment with Liprimar, you should try to control hypercholesterolemia through diet, exercise and weight loss in obese patients, as well as treatment of the underlying disease.
When prescribing the drug, the patient should recommend a standard lipid-lowering diet, which he must follow during treatment.
The drug can be taken at any time of the day, regardless of food intake. The dose of the drug (from 10 to 80 mg 1 time / day) is selected taking into account the initial levels of LDL-C, the purpose of therapy and the individual effect. At the beginning of treatment and / or during an increase in the dose 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 in most patients, the necessary effect can be achieved with Liprimar at a dose of 10 mg 1 time / day. The therapeutic effect is manifested within 2 weeks and usually reaches a maximum within 4 weeks. With prolonged treatment, the effect persists.
Patients with homozygous familial hypercholesterolemia are prescribed a dose of 80 mg 1 time / day (in most cases, therapy led to a decrease in the level of LDL-C by 18-45%.
Impaired renal function does not affect plasma atorvastatin levels or the degree of decrease in LDL-C when using Liprimar, therefore, dose changes are not required.
When using the drug in elderly patients, there were no differences in safety, effectiveness or achievement of the goals of lipid-lowering therapy in comparison with the general population.
Side effects
From the side of the central nervous system: insomnia, headache, asthenic syndrome.
From the digestive tract: nausea, diarrhea, abdominal pain, dyspepsia, constipation, flatulence.
From the musculoskeletal system and connective tissue: myalgia.
Less frequent adverse reactions ( 1%)
From the side of the central nervous system and peripheral nervous system: malaise, dizziness, amnesia, paresthesia, peripheral neuropathy, hypesthesia.
From the digestive tract: vomiting, anorexia, hepatitis, pancreatitis, cholestatic jaundice.
From the musculoskeletal system and connective tissue: back pain, muscle cramps, myositis, myopathy, arthralgia, rhabdomyolysis.
Allergic reactions: urticaria, pruritus, rash, anaphylactic reactions, bullous rash, polymorphic exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).
From the side of metabolism: hypoglycemia, hyperglycemia, increased serum creatine phosphokinase (CPK).
From the hemopoietic organs: thrombocytopenia.
Other: impotence, peripheral edema, weight gain, chest pain, secondary renal failure, alopecia, tinnitus, increased fatigue.
Drug Interaction
The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases with the concomitant use of cyclosporine, fibrates, erythromycin, clarithromycin, antifungal agents – azole derivatives, and nicotinosine.
CYP3A4 isoenzyme isoenzyme inhibitors. Because atorvastatin is metabolized by the cytochrome CYP3A4 isoenzyme, co-administration of atorvastatin with CYP3A4 cytochrome isoenzyme inhibitors may lead to increased plasma concentrations of atorvastatin. The degree of interaction and potentiation effect is determined by the variability of the effect on the cytochrome CYP3A4 isoenzyme.
OATP1B1 transport protein inhibitors. Atorvastatin and its metabolites are substrates of the transport protein OATP1B1. OATP1B1 inhibitors (eg cyclosporine) may 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 (see “Method of administration and dose”).
Erythromycin / clarithromycin. With concomitant use of atorvastatin and erythromycin (500 mg 4 times a day) or clarithromycin (500 mg 2 times a day), which inhibit the cytochrome isoenzymeCYP3A4, an increase in the concentration of atorvastatin in the blood plasma was observed (see “Special Instructions”).
Protease inhibitors. The concomitant use of atorvastatin with protease inhibitors known as CYP3A4 cytochrome isoenzyme inhibitors is accompanied by an increase in the plasma concentration of atorvastatin (concomitantly increased by 40% with atorvastatin erythromycin Cmax).
Diltiazem. Co-administration of atorvastatin at a dose of 40 mg with diltiazem at a dose of 240 mg leads to an increase in the concentration of atorvastatin in the blood plasma.
Cimetidine. No clinically relevant interaction of atorvastatin with cimetidine was found.
Itraconazole. Concomitant administration of atorvastatin at doses of 20 to 40 mg and itraconazole at a dose of 200 mg increased the atorvastatin AUC.
Grapefruit juice. Because grapefruit juice contains one or more components that inhibit the cytochrome CYP3A4 isoenzyme, its excessive intake (more than 1.2 liters per day) may cause an increase in the concentration of atorvastatin in the blood plasma.
Cytochrome CYP3A4 isoenzyme inducers. Co-administration of atorvastatin with cytochrome isoenzyme inducers of CYP3A4 (eg efavirenz or rifampicin) may lead to a decrease in the concentration of atorvastatin in blood plasma. Due to the dual mechanism of interaction with rifampicin (CYP3A4 cytochrome isoenzyme inducer and hepatocyte transport protein inhibitor OATP1B1), atorvastatin and rifampicin are recommended simultaneously, as delayed administration of atorvastatin after taking rifampicin results in a significant decrease in the concentration of atorvastatin in the blood plasma.
Antacids. Concomitant intake of magnesium hydroxide and aluminum hydroxide suspension reduced the concentration of atorvastatin in the blood plasma by about 35%, but the degree of reduction of the Xc-LDL content did not change.
Phenazon. Atorvastatin does not affect the pharmacokinetics of phenazone, so interaction with other drugs metabolised by the same cytochrome isoenzymes is not expected.
Colestipol. When co-administered with colestipol, the concentration of atorvastatin in the blood plasma decreased by about 25%, however, the hypolipidemic effect of the combination of atorvastatin and colestipol was superior to that of each drug separately.
Digoxin. Repeated administration of digoxin and atorvastatin at a dose of 10 mg Css digoxin in 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 follow-up.
Azithromycin. With atorvastatin 10 mg once daily and azithromycin 500 mg once daily, the plasma concentration of atorvastatin did not change.
Oral contraceptives. With the concomitant use of atorvastatin and oral contraceptive containing norethisterone and ethinylestradiol, there was a significant increase in the AUC of norethisterone and ethinylestradiol by about 30 and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman taking atorvastatin.
Terfenadine. No clinically relevant changes in the pharmacokinetics of terfenadine were observed with atorvastatin and terfenadine.
Warfarin. No evidence of a clinically relevant interaction of atorvastatin with warfarin was found.
Amlodipine. Atorvastatin 80 mg and amlodipine 10 mg atorvastatin pharmacokinetics did not change at steady state.
Another concomitant therapy. In clinical trials, atorvastatin was used in combination with antihypertensive agents and estrogens in the context of replacement therapy for signs of clinically significant undesirable interaction. No interaction studies were observed with other specific drugs.
overdose
Treatment: There is no specific antidote for the treatment of overdose with Liprimar ®.
In case of overdose, symptomatic treatment should be performed as needed. Because the drug actively binds to plasma proteins, hemodialysis is ineffective.
Storage conditions
Store at a temperature not exceeding 25 ° C, out of the reach of children.
Shelf suitability
3 Year
Deystvuyuschee substances
Atorvastatin
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