Liprimar pills 80 mg 30 pcs
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Active ingredients
Atorvastatin
Release form
Pills
Composition
Active ingredient: Atorvastatin. Concentration of active ingredient (mg): 80 mg
Pharmacological effect
Pharmacological action - cholesterol, hypolipidemic.
Pharmacokinetics
Suction. Atorvastatin is rapidly absorbed after oral administration: Tmax in blood plasma - after 1–2 hours. In women, Cmax is 20% higher and AUC is 10% lower than in men. The degree of absorption and concentration in the blood plasma increase in proportion to the dose. Absolute bioavailability is about 14%, and systemic bioavailability of the inhibitory activity on HMG-CoA reductase is about 30%. Low systemic bioavailability is caused by presystemic metabolism in the gastrointestinal mucosa and / or during the first passage through the liver. Food somewhat reduces the rate and extent of absorption of the drug (by 25 and 9%, respectively, as evidenced by the results of Cmax and AUC, but lowering low-density lipoprotein cholesterol (Xc-LDL) is similar to that when taking atorvastatin on an empty stomach. Despite the fact that atorvastatin in the evening its plasma concentration is lower (Cmax and AUC, approximately 30%) than after taking it in the morning, the decrease in Xc-LDL does not depend on the time of day at which the drug is taken. Distribution. Atorvastatin Vd is average with It absorbs about 381 L. Communication with plasma proteins is at least 98%. The ratio of the content in erythrocytes / plasma is about 0.25, i.e. atorvastatin does not penetrate into erythrocytes poorly. Metabolism. Atorvastatin is largely metabolized to form ortho para-hydroxylated derivatives and various β-oxidation products In vitro ortho- and para-hydroxylated metabolites have an inhibitory effect on HMG-CoA reductase comparable to that of atorvastatin. Approximately 70% reduction in the activity of HMG-CoA reductase occurs due to the action of active circulating metabolites. The results of in vitro studies suggest that liver cytochrome CYP3A4 isoenzyme plays an important role in atorvastatin metabolism. This is evidenced by an increase in the concentration of the drug in the blood 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 cytochrome CYP3A4 isoenzyme. Atorvastatin does not have a clinically significant effect on plasma concentration of terfenadine, which is metabolized mainly with the participation of cytochrome CYP3A4 isoenzyme, therefore its significant effect on the pharmacokinetics of other cytochrome CYP3A4 isoenzyme is unlikely (see the Interaction section). Inference. Atorvastatin and its metabolites are excreted mainly with bile after hepatic and / or extrahepatic metabolism (atorvastatin is not subject to severe enterohepatic recirculation). T1 / 2 of the drug 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 ingestion in the urine is detected less than 2% of the dose of the drug. Special patient groups: Elderly patients. Atorvastatin concentrations in the blood plasma of patients older than 65 years are higher (Cmax - approximately 40%, AUC - approximately 30%) than in adult patients of young age. Differences in the efficacy and safety of the drug or the achievement of lipid-lowering therapy goals in elderly patients compared with the general population have not been identified. Children. Studies of the pharmacokinetics of the drug in children were not conducted. Kidney failure. Impaired renal function does not affect the concentration of atorvastatin in the blood plasma or its effect on lipid metabolism, therefore, the dose change in patients with impaired renal function is not required (see “
Dosage and administration
”). Atorvastatin is not excreted during hemodialysis due to intense binding to plasma proteins. Liver failure. The concentration of the drug is significantly increased (Cmax - about 16 times, AUC - about 11 times) in patients with alcoholic cirrhosis of the liver (stage B according to the Child-Pugh classification) (see "Contraindications").Indications
Primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia (Frederickson type IIa). Combined (mixed) hyperlipidemia (Frederickson type IIa and IIb types). Disbetalipoproteinemiya (III type Frederickson type III), a heartbrooxypoproteinemia (type III Frederickson type Frederickson type III) has a 4-day, 4-day, 4-day Frederickson type, Frederickson dysfunctional hypercholesterolemia.Familial endogenous hypertriglyceridemia (type IV by Frederickson), resistant to diet. 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 dependence, arterial hypertension, diabetes mellitus, low concentrations of Xc-HDL in plasma, genetic predisposition, in t. h on the background of 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.
Contraindications
Hypersensitivity to any component of the drug. An active liver disease or an increase in the activity of “liver” transaminases in the blood plasma of unknown origin is more than 3 times as compared with the upper limit of the norm. Age up to 18 years (not enough clinical data on the efficacy and safety of the drug in this age group). With caution In patients who abuse alcohol. in patients with a history of liver disease.
Precautionary measures
Before and during treatment, it is necessary to monitor indicators of liver function. Liver function should be examined for signs of liver damage. If transaminases increase, their activity should be monitored until it is normalized. If the increase in the activity of ACT or ALT more than 3 norms is maintained, a dose reduction or cancellation of LIPRIMAR is recommended. In patients who abuse alcohol and / or suffer from liver disease, LIPRIMAR * should be used with caution. Effects on skeletal muscle: Patients who received LIPRIMAR * had myalgias that did not lead to complications. Therapy LIPRIMAR * should be stopped in case of a pronounced increase in the activity of CPK or the development of myopathy (or the assumption of its presence). When signs of myopathy appear, the activity of CPK should be determined. If a significant increase in the level of CPK is maintained, then it is recommended to reduce the dose or cancel LIPRIMAR *.When taking other drugs of this class are described cases of rhabdomyolysis and secondary renal failure caused by myoglobulinuria.
Use during pregnancy and lactation
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 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 necessary, the appointment of the drug during lactation breastfeeding should be stopped to avoid the risk of adverse events in infants.
Dosage and administration
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 patients with obesity, as well as therapy of the underlying disease. When prescribing the drug, the patient should be advised to recommend a standard cholesterol-lowering diet, which he should follow during the entire period of therapy. The dose of the drug varies from 10 mg 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 on the therapy being administered. The maximum daily dose for a single dose is 80 mg. At the beginning of treatment or during the dose increase of the drug Liprimar, it is necessary every 2-4 weeks to monitor the level of lipids in the blood plasma and adjust the dose of the drug accordingly. Primary hypercholesterolemia and combined (mixed) hyperlipidemia For most patients - 10 mg 1 time per day. therapeutic effect occurs within 2 weeks and usually reaches a maximum within 4 weeks. With long-term treatment, the effect is preserved. Homozygous familial hypercholesterolemia. In most cases, prescribed 80 mg 1 time per day (a decrease in the content of LDL-C on 18-45%). Liver failure. In case of insufficient liver function, the dose of Liprimar should be reduced, with constant monitoring of the activity of “liver” transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT). Kidney failure.Impaired renal function does not affect the concentration of atorvastatin in the blood plasma or the degree of decrease in the level of LDL-LDL during therapy with Liprimar, therefore, dose adjustment of the drug is not required. Elderly patients. No differences in efficacy, safety or therapeutic effect of Liprimar in elderly patients compared with the general population were found and dose adjustment is not required (see the Pharmacokinetics section). Use in combination with other drugs. If necessary, the joint use with cyclosporine dose of Liprimar should not exceed 10 mg (see section "Special instructions"). Recommendations for determining treatment goals. A. Recommendations of the US National Cholesterol Education Program NCEP Risk Category Targeted Content Xc-LDL (mgdl) Xc-LDL Contents, which recommends a lifestyle change (mgdl) Xc-LDL Content, at which pharmacotherapy is recommended (mgdl). IHD or the risk of IHD (10-year risk> 20%) <100 ≥100 ≥130 (100-129: pharmacotherapy is possible) 1. More than 2 risk factors (10-year risk ≤ 20%) <130 ≥130 10-year risk 10% -20%: ≥130 10-year risk <10%: ≥1600-1 risk factor2 <160 ≥160 ≥ 190 (160-189: prescribe a drug that reduces the content of Xc-LDL). Some experts recommend the use of lipid-lowering agents that reduce the content of Xc-LDL, if the lifestyle change does not reduce its content to <100 mgdl. Others prefer drugs that have a predominant effect on TG and Xc-HDL, such as nicotinic acid and fibrates. The physician may also postpone pharmacotherapy in this subgroup. 2 In the absence of risk factors or the presence of only one risk factor in almost all people, the 10-year risk is <10%, therefore its assessment is not required. If the target content of Xc-LDL is reached, and the TG content is kept> 200 mgdl, then the secondary goal of therapy is to reduce cholesterol, excluding Xc-HDL (total cholesterol - Xc-HDL), to a level that exceeds the target content of Xc-LDL by 30 mgdl in each risk category. B. Recommendations of the European Society of Atherosclerosis In patients with a confirmed diagnosis of coronary artery disease and in patients with a high risk of ischemic complications, the goal of therapy is to reduce LDL-C LDL to less than 3 mmol (or less than 115 mgdl) and total cholesterol to less than 5 mmol (or less than 190 mgdl).
Side effects
Liprimar is usually well tolerated. adverse reactions are usually mild and transient.The most frequent adverse reactions (> 1%): From the side of the central nervous system: insomnia, headache asthenic syndrome. On the part of the gastrointestinal tract: nausea, diarrhea, abdominal pain, dyspepsia, constipation, flatulence. From the musculoskeletal system and connective tissue: myalgia. Less frequent adverse reactions (£ 1%): On the part of the central and peripheral nervous system: malaise, dizziness, amnesia, paresthesia, peripheral neuropathy, hypoesthesia. On the part of the digestive tract: vomiting, anorexia, hepatitis, pancreatitis, cholestatic jaundice. On the part of 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). Metabolism: hypoglycemia, hyperglycemia, increased serum creatine phosphokinase (CK). From the side of blood-forming organs: thrombocytopenia. Others: impotence, peripheral edema, weight gain, chest pain, secondary renal failure, alopecia, tinnitus, fatigue.
Overdose
Treatment: there is no specific antidote for the treatment of drug overdose 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.
Interaction with other drugs
The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases with simultaneous use of cyclosporine, fibrates, erythromycin, clarithromycin, antifungal agents derived from azole, and nicotinic acid in lipid-lowering doses (see "Special instructions"). Inhibitors of cytochrome CYP3A4 isoenzyme. Since atorvastatin is metabolized by the cytochrome CYP3A4 isoenzyme, the combined use of atorvastatin with cytochrome CYP3A4 isoenzyme inhibitors can lead to an increase in plasma atorvastatin concentration. 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 OATP1B1.Atorvastatin and its metabolites are substrates of the transport protein OATP1B1. OATP1B1 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 (see "
Dosage and administration
"). 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 the plasma concentration of atorvastatin was observed (see "Special instructions"). 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 of atorvastatin with erythromycin Cmax 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 atorvastatin concentration. Cimetidine Clinically significant interaction of atorvastatin with cimetidine was not detected. Itraconazole. The simultaneous use of atorvastatin in doses of 20 to 40 mg and itraconazole at a dose of 200 mg led to an increase in the AUC value of atorvastatin. Grapefruit juice. Since 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 concentrations. Inductors of cytochrome CYP3A4 isoenzyme. The combined use of atorvastatin with inducers of cytochrome CYP3A4 isoenzyme (for example, efavirenz or rifampicin) can lead to a decrease in plasma levels of atorvastatin. Due to the dual mechanism of interaction with rifampicin (cytochrome CYP3A4 isoenzyme inducer and inhibitor of hepatocyte transport protein OATP1B1), simultaneous use of atorvastatin and rifampicin is recommended, since delayed atorvastatin administration after taking rifampicin leads to a significant decrease in atorvastatin concentration in the blood plasma. Antacids. Simultaneous ingestion of a suspension containing magnesium hydroxide and aluminum hydroxide, reduced the concentration of atorvastatin in the blood plasma by about 35%, but the degree of reduction in the content 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 in a dose of 10 mg Css 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 at a dose of 10 mg 1 time per day and azithromycin at 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, there were no clinically significant changes in the pharmacokinetics of terfenadine. Warfarin. Signs of clinically significant interaction of atorvastatin with warfarin not detected. Amlodipine. With simultaneous use of atorvastatin at a dose of 80 mg and amlodipine at a dose of 10 mg, the pharmacokinetics of atorvastatin in an equilibrium state did not change. 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; studies of interaction with other specific drugs have not been conducted.special instructions
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 as compared with VGN) increases in the activity of hepatic transaminases AST and ALT were noted.A persistent increase in the serum content of hepatic transaminases (more than 3 times compared with VGN) was observed in 0.7% of patients who received the drug Liprimar. The frequency of such changes when using the drug in doses of 10, 20, 40 and 80 mg was 0.2; 0.2; 0.6 and 2.3%, respectively. Increased liver transaminase activity is usually not accompanied by jaundice or other clinical manifestations. At lower doses, temporary or complete withdrawal of the drug Liprimar, the activity of hepatic transaminases returned to its original level. Most patients continued to take the drug Liprimar in a reduced dose without any clinical consequences. Before starting therapy, after 6 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 case of an increase in the level of hepatic transaminases, their activity should be monitored until it is normalized. If the increase in AST or ALT activity is more than 3 times as compared with VGN is maintained, a dose reduction or withdrawal of the drug Liprimar is recommended (see “Side Effects”). 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 (see section "Contraindications"). Action on skeletal muscle. In patients receiving the drug Liprimar, myalgia was noted (see "Side effect"). The diagnosis of myopathy (muscle pain or muscle weakness in combination with an increase in the activity of CPK more than 10 times compared to VGN) should be assumed in patients with diffuse myalgia, muscle soreness or weakness and / or a pronounced increase in the activity of CPK. Therapy with Liprimar should be discontinued in the 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 the 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 Liprimar in combination with fibrates, erythromycin, immunosuppressants, azole antifungal agents or lipid-lowering doses of nicotinic acid, the doctor must carefully weigh the expected benefit of 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 (see “Interaction”). 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 or a risk factor for the development of renal failure occur in the presence of 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. 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. Influence on the ability to drive a car or perform work that requires increased speed of physical and mental reactions. There is no data on the effect of atorvastatin on the ability to drive a car and engage in potentially hazardous activities that require increased concentration and psychomotor speed.