Liprimar 10mg coated pills N100
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Active ingredients
Atorvastatin
Release form
Pills
Composition
Atorvastatin calcium 10.85 mg; which corresponds to the content of atorvastatin 10 mg; excipients: calcium carbonate - 33 mg, microcrystalline cellulose - 60 mg, lactose monohydrate - 32.8 mg, croscarmellose sodium - 9 mg, polysorbate 80 - 0.6 mg, hyprolosis - 3 mg, magnesium stearate - 0.75 mg The film coating composition: white ys-1-7040 opadry (hypromellose - 66.12%, polyethylene glycol - 18.9%, titanium dioxide - 13.08%, talc - 1.9%) - 4.47 mg, simethicone emulsion (simethicone - 30%, stearic emulsifier - 0.075%, sorbic acid, water) - 0.03 mg, candelic wax - 0.08 mg.
Pharmacological effect
Synthetic lipid-lowering drug. Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, a key enzyme that can also be converted into the use of a mixture of 3-hydroxy-3-methylglutaryl-CoA and mevalonate, a precursor of steroids, including cholesterol. lowers plasma concentration of total cholesterol (Xc), Xc-LDL and apolipoprotein B (apo-B), as well as Xc-VLDL and TG, causes an increase in the concentration of Xc-HDL. Atorvastatin reduces Xc and LDL-LDL in 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 capture and catabolism of Xc-LDL. Atorvastatin reduces the formation of LDL and 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 concentration of Xc-LDL in patients with homozygous hereditary hypercholesterolemia resistant to other lipid-lowering drugs. Atorvastatin at doses of 10-80 mg reduces the concentration of Xc by 30-46%, Xc-LDL - by 41-61%, apo-B - on 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 type 2 diabetes. In patients with isolated hypertriglyceridemia, atorvastatin reduces the concentration of total cholesterol, LDL-C, LDL-C, LDLA, apo-B, and TG and increases the LDL-C levels.In patients with dysbetalipoproteinemia, it lowers intermediate-density lipoprotein cholesterol (Xc-LPPP) .; In patients with type IIa and IIb hyperlipoproteinemia, according to Fredrickson classification, the mean value of increased HD-COL concentration during treatment with atorvastatin (10-80 mg) compared to baseline makes 5.1-8.7% and does not depend on a dose. 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.; Atorvastatin at a dose of 80 mg reliably reduces the risk of ischemic complications and mortality by 16% after a 16-week course, and the risk of re-hospitalization for angina, accompanied by signs of myocardial ischemia, by 26% (a study to reduce the severity of myocardial ischemia during intensive lipid-lowering therapy (MIRACL)). Atorvastatin causes a reduction in the risk of ischemic complications and mortality (in patients with myocardial infarction without a Q-wave and unstable angina, in men and women, patients younger than 65 years old) in patients with different initial concentrations of LDL-C-LDL; Xc-LDL correlates better with the dose of the drug than with its concentration in the blood plasma. The dose is selected based on the therapeutic effect.; 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; Atorvastatin in a dose of 10 mg reduces fatal and non-fatal heart attacks in comparison with placebo in patients with arterial hypertension and three or more risk factors (Anglo-Scandinavian study on the outcome of cardiac diseases (ASCOT-LLA); In patients with atorvastatin IHD at a dose of 80 mg / day) leads to a decrease in the total volume of atheroma by 0.4% in 1.8 months of therapy (a study on the reverse development of coronary atherosclerosis with intensive lipid-lowering therapy (REVERSAL)); Recurrent stroke; Atorvastatin at a dose of 80 mg / day reduces the risk of repeated fatal or nonfatal stroke in patients after a stroke or transient ischemic attack (TIA) without a history of ischemic heart disease (a study on the prevention of stroke with an intense decrease in cholesterol concentration (SPARCL)), by 16% compared with placebo. This significantly reduces the risk of major cardiovascular disorders and revascularization procedures.Reducing the risk of cardiovascular disorders during therapy with atorvastatin is noted in all groups of patients, except the one where patients with primary or recurrent hemorrhagic stroke are included.
Pharmacokinetics
Absorption; Atorvastatin is rapidly absorbed after oral administration: the time to reach it Cmax is 1-2 hours. The degree of absorption and the concentration of atorvastatin in the blood plasma increase 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 Cmax and AUC), but the decrease in Xc-LDL is similar to that when taking atorvastatin on an empty stomach. Although after taking atorvastatin in the evening, its plasma concentration is lower (Cmax and AUC by about 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's average Vd is about 381 liters. Atorvastatin binding to plasma proteins is at least 98%. The ratio of atorvastatin in erythrocytes / blood plasma is about 0.25, i.e. atorvastatin poorly penetrates red blood cells.; Metabolism; Atorvastatin is largely metabolized to form ortho- and para-hydroxylated derivatives and various beta-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 CYP3A4 isoenzyme plays an important role in atorvastatin metabolism. In favor of this fact, an increase in the plasma concentration of atorvastatin is shown, 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 does not have a clinically significant effect on the plasma concentration of terfenadine, which is metabolized mainly by the CYP3A4 isoenzyme, therefore its significant effect on atorvastatin on the pharmacokinetics of other substrates of the CYP3A4 isoenzyme is unlikely.; Excretion; / or extrahepatic metabolism (atorvastatin is not subject to severe enterohepatic recirculation). T1 / 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 ingestion in the urine, less than 2% of the accepted dose of the drug is found.; Pharmacokinetics in special clinical situations; Patients of advanced age. Atorvastatin plasma concentrations in patients over the age of 65 are higher (Cmax by about 40%, AUC by about 30%) than in adult patients of young age. There were no differences in safety, efficacy, or achievement of lipid-lowering therapy goals in elderly patients compared to the general population. Children. In an 8-week open-label study, children (6–17 years old) with heterozygous familial hypercholesterolemia and baseline LDL cholesterol concentrations ≥4 mmol / l received atorvastatin therapy as 5 mg or 10 mg chewable pills or coated pills at a dose of 10 mg or 20 mg 1 time / day, respectively. The only significant covariate in the pharmacokinetic model of the population receiving atorvastatin was body weight. The apparent clearance of atorvastatin in children did not differ from that in adult patients with allometric measurement by body weight. In the range of action of atorvastatin and o-hydroxyatorvastatin, a consistent decrease in Xc-LDL and Xc was observed. At women, Cmax of atorvastatin is 20% higher and AUC is 10% less than in men.; Impairment of renal function. 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 has not been studied in patients with end-stage renal disease.Atorvastatin is not excreted during hemodialysis due to intense binding to plasma proteins. Liver dysfunction. Atorvastatin concentration is significantly increased (Cmax approximately 16, AUC approximately 11 times) in patients with alcoholic cirrhosis of the liver (class B on the Child-Pugh scale). Hepatic seizure of all HMG-CoA rduktazy inhibitors, including atorvastatin, occurs with the participation of the OATP1B1 transporter. Patients with the SLCO1B1 genetic polymorphism are at risk of increasing atorvastatin exposure, which may lead to an increased risk of rhabdomyolysis. Polymorphism of the gene encoding OATP1B1 (SLCO1B1 c.521CC) is associated with an increase in exposure (AUC) of atorvastatin by a factor of 2.4 compared with patients without such a genotypic change (c.521TT). Disorders of atorvastatin uptake by the liver due to genetic disorders can also occur in these patients. Possible effects on effectiveness are unknown.
Indications
Hypercholesterolemia:; - as a supplement to a diet to lower elevated total cholesterol, LDL-C, LDL-apo-B, and triglycerides in adults, adolescents, and children 10 years of age or older with primary hypercholesterolemia, including familial hypercholesterolemia (heterozygous variant) or combined ( mixed) hyperlipidemia (respectively type IIa and IIb according to Fredrickson's classification), when the response to diet and other non-drug therapies are insufficient ;; - to lower elevated total cholesterol, LDL-LDL in adults with homozygos familial hypercholesterolemia as an adjunct to other lipid-lowering methods of treatment (for example, LDL-apheresis) or if such treatments are not available.; Prevention of cardiovascular diseases: - Prevention of cardiovascular events in adult patients with a high risk of developing primary cardiovascular diseases. vascular events, as a supplement to the correction of other risk factors ;; - secondary prevention of cardiovascular complications in patients with coronary artery disease in order to reduce mortality, myocardial infarction, stroke, repeated hospitalizations for angina and the need for revascularization.
Contraindications
- hypersensitivity to the components of the drug ;; - active liver disease or increased activity of hepatic transaminases in plasma of unclear genesis more than 3 times compared with VGN ;; - pregnancy ;; - breastfeeding period ;; - women of childbearing age,not using adequate methods of contraception ;; - age up to 18 years (there is insufficient clinical data on the efficacy and safety of the drug in this age group), with the exception of heterozygous familial hypercholesterolemia (use contraindicated in children under 10 years old) ;; - simultaneous use with fusidic acid ;; - congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption.; With caution; In patients who abuse alcohol; in patients with a history of liver disease. In patients with risk factors for the development of rhabdomyolysis (renal dysfunction, hypothyroidism, hereditary muscle disorders in a patient in history or family history, already transferred toxic effects of HMG-CoA reductase inhibitors (statins) or fibrates on muscle tissue, a history of liver disease and / or patients who consume significant amounts of alcohol, age over 70 years, situations in which atorvastatin plasma levels are expected to increase (for example, interactions with other drugs).
Use during pregnancy and lactation
Liprimar is contraindicated for use during pregnancy and lactation (breastfeeding); women of reproductive age should use adequate methods of contraception during treatment. The use of the drug Liprimar is contraindicated in women of childbearing age who do not use adequate methods of contraception. There have been rare cases of congenital anomalies after exposure to HMG-CoA reductase inhibitors (statins) on the fetus in utero. Animal studies have shown toxic effects on reproductive function.; 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
The drug is taken orally at any time of the day, regardless of the meal. Before 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 a drug, the patient should be recommended a standard hypocholesterolemic diet, which he must follow during the entire period of therapy.; The dose of the drug varies from 10 mg to 80 mg 1 time / day and titrated taking into account the concentration of LDL-C, goals of therapy and individual response to therapy. The maximum dose is 80 mg / day. At the beginning of treatment and / or during a dose increase of Liprimar it is necessary to monitor plasma concentration of lipids every 2-4 weeks and adjust the dose accordingly. For primary hypercholesterolemia and combined (mixed) hyperlipidemia for most Patients recommended dose of Liprimar is 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. In case of homozygous familial hypercholesterolemia, the drug is prescribed in most cases at a dose of 80 mg 1 time / day (a decrease in the concentration of LDL-C on 18-45%); In heterozygous familial hypercholesterolemia, the initial dose is 10 mg / day The dose should be selected individually and evaluate the relevance of the dose every 4 weeks with a possible increase to 40 mg / day. Then either the dose can be increased to a maximum of 80 mg / day, or it is possible to combine bile acid sequestrants with atorvastatin at a dose of 40 mg / day; Prevention of cardiovascular diseases: in primary prevention studies, the dose of atorvastatin was 10 mg / day. You may need to increase the dose in order to achieve the values of Xc-LDL, corresponding to the current recommendations. Use for children from 10 to 18 years old with heterozygous familial hypercholesterolemia: the recommended initial dose is 10 mg 1 time / day. The dose may be increased to 20 mg / day, depending on the clinical effect. Experience with a dose of more than 20 mg (corresponding to a dose of 0.5 mg / kg) is limited. The dose of the drug should be titrated depending on the purpose of lipid-lowering therapy. Dose adjustment should be carried out at intervals of 1 time per 4 weeks or more.; In hepatic insufficiency, the dose of Liprimar should be reduced under the constant control of ACT and ALT activity; Dysfunction of the kidneys does not affect atorvastatin plasma levels or the degree of Xc decrease. LDL when applying Liprimar,therefore, dose adjustment of the drug is not required.; When using the drug in elderly patients, no differences in efficacy and safety compared with the general population were found, and dose adjustment is not required.; Use in combination with other drugs; If necessary, combined use with cyclosporine, telaprevir or tipranavir / ritonavir combination dose of Liprimar should not exceed 10 mg / day; use caution and apply the lowest effective dose of atorvastatin in one provisional application of HIV protease inhibitors, HCV protease inhibitors (boceprevir), clarithromycin and itraconazole.
Side effects
Liprimar is usually well tolerated. Side effects are usually mild and transient. Determination of the frequency of adverse reactions: often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100), rarely (≥1 / 10 000 to <1/1000), very rarely (≤1 / 10 000), unknown - impossible to estimate based on available data. From the nervous system: often - headache; infrequently - dizziness, paresthesia, hypesthesia, disturbance of taste perception, amnesia; rarely, peripheral neuropathy; unknown - loss or loss of memory. Psychiatric disorders: infrequently - nightmares, insomnia; unknown - depression.; On the part of the organ of vision: infrequently - the appearance of a "veil" before the eyes; rarely - visual impairment. On the part of the organ of hearing and labyrinth disorders: infrequently - tinnitus; very rarely - hearing loss. On the part of the respiratory system: often - sore throat, nosebleeds; unknown - isolated cases of interstitial lung disease (usually with long-term use); On the part of the digestive system: often - constipation, flatulence, dyspepsia, nausea, diarrhea; infrequently - vomiting, abdominal pain, belching, pancreatitis, abdominal discomfort. From the side of the liver and biliary tract: infrequently - hepatitis; rarely - cholestasis; very rarely - secondary renal failure. From the skin and subcutaneous tissues: infrequently - urticaria, pruritus, rash, alopecia; rarely - angioedema, bullous rash, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome); From the musculoskeletal system: often myalgia, arthralgia,limb pain, muscle cramps, joint swelling, back pain, musculoskeletal pain; infrequently - neck pain, muscle weakness; rarely - myopathy, myositis, rhabdomyolysis, tendinopathy (in some cases with a tendon rupture); unknown - immune-mediated necrotizing myopathy. From the genital organs and the mammary gland: infrequently - impotence; very rarely - gynecomastia. From the immune system: often - allergic reactions; very rarely - anaphylaxis.; From the side of metabolism: often - hyperglycemia; infrequently - hypoglycemia, weight gain, anorexia; unknown - diabetes mellitus: the incidence of development depends on the presence or absence of risk factors (fasting blood glucose concentration ≥ 5.6 mmol / l, BMI> 30 kg / m2, elevated triglyceride concentration, history of hypertension); From the hematopoietic system: rarely thrombocytopenia.; Infections and invasions: often - nasopharyngitis.; General disorders: infrequently - malaise, asthenic syndrome, chest pain, peripheral edema, increased fatigue, fever.; Laboratory and instrumental data: often - abnormal rezul test hepatic tests (AST and ALT), increased activity of serum CPK; infrequently - leukocyturia; unknown - increase in the concentration of glycated hemoglobin (HbA1); Children; Adverse reactions associated with taking the drug Liprimar in quantity did not differ from reactions in patients receiving placebo. The most frequent reactions, regardless of the frequency of control, were infections.
Overdose
Treatment: there is no specific antidote. If necessary, conduct symptomatic therapy. It should conduct functional tests of the liver and monitor the activity of CPK. Since the drug is actively associated with plasma proteins, hemodialysis is ineffective.
Interaction with other drugs
During treatment with HMG-CoA reductase inhibitors, the risk of myopathy increases with simultaneous use of cyclosporine, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day) or inhibitors of the CYP3A4 isoenzyme (including erythromycin, clarithromycin, antifungal preparations of azole derivatives) .; CYP3A4 isoenzyme inhibitors; Since atorvastatin is metabolized by the CYP3A4 isoenzyme, the combined use of the drug with inhibitors of this isoenzyme can lead to an increase in plasma atorvastatin concentration.The degree of interaction and the effect of potentiation are determined by the variability of effects on the CYP3A4 isoenzyme.; It was found that potent inhibitors of the CYP3A4 isoenzyme lead to a significant increase in plasma atorvastatin concentrations. It is possible to avoid the simultaneous application of potent inhibitors of isoenzyme CYP3A4 (e.g., cyclosporine, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir). If concurrent administration of these drugs is necessary, consideration should be given to initiating therapy with a minimum dose, and the possibility of reducing the maximum dose of atorvastatin should be evaluated. Moderate inhibitors of the CYP3A4 isoenzyme (for example, erythromycin, diltiazem, verapamil and fluconazole) can lead to an increase in plasma atorvastatin concentration blood. Against the background of the simultaneous use of HMG-CoA reductase inhibitors (statins) and erythromycin, an increased risk of myopathy was noted. No studies of amiodarone or verapamil and atorvastatin have been conducted. Both amiodarone and verapamil are known to inhibit the activity of the CYP3A4 isoenzyme, and the simultaneous use of these drugs with atorvastatin may lead to an increase in the exposure of atorvastatin. In this regard, it is recommended to reduce the maximum dose of atorvastatin and to conduct appropriate monitoring of the patient's condition while using it with moderate inhibitors of the CYP3A4 isoenzyme. Control should be carried out after initiation of therapy and amid a change in the dose of the inhibitor.; Inhibitors of the transport protein OATP1B1; 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. The effect of suppressing the function of transporters of hepatic capture on the concentration of atorvastatin in hepatocytes is unknown. If it is impossible to avoid the simultaneous use of such drugs, it is recommended to reduce the dose and monitor the effectiveness of therapy.; Gemfibrozil / fibrates; Against the background of the use of fibrates as a monotherapy, adverse reactions have been noted periodically, including rhabdomyolysis concerning the musculoskeletal system.The risk of such reactions increases with the simultaneous use of fibrates and atorvastatin. If the simultaneous use of these drugs cannot be avoided, then the minimum effective dose of atorvastatin should be used, as well as regular monitoring of the patient’s condition.; Ezetimibe; Ezetimibe use is associated with the development of adverse reactions, including rhabdomyolysis, from the musculoskeletal system. The risk of such reactions increases with the simultaneous use of ezetimiba and atorvastatin. For these patients, careful monitoring is recommended.; Erythromycin / clarithromycin; With simultaneous use of atorvastatin and erythromycin (500 mg 4 times / day) or clarithromycin (500 mg 2 times / day), an increase in the concentration of atorvastatin in the blood plasma was observed. ; Protease inhibitors; Simultaneous use of atorvastatin with protease inhibitors, known as CYP3A4 inhibitors, is accompanied by an increase in plasma concentration of atorvastatin.; Diltiazem; Combined use of atorvastatin at a dose of 40 mg with diltiazem ohm at a dose of 240 mg leads to an increase in plasma concentration of atorvastatin.; Cimetidine; Clinically significant interaction of atolrvastatin with cimetidine was not detected.; Itraconazole; Simultaneous use of atorvastatin at doses from 20 mg to 40 mg and itraconazole at a dose of 200 mg led to an increase in AUC atorvastatin.; Grapefruit juice; Since grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme, its excessive consumption (more than 1.2 l / day) can cause an increase in the concentration of atorvastatin in the PL blood cyst.; CYP3A4 cytochrome isoenzyme inducers; Combined use of atorvastatin with cytochrome CYP3A4 isoenzyme inducers (for example, efavirenz or rifampicin or St. John's wort perforated drugs) can lead to a decrease in atorvastatin plasma levels. 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 results in a significant decrease in atorvastatin concentration in the blood plasma.However, the effect of rifampicin on the concentration of atorvastatin in hepatocytes is unknown, and if simultaneous use cannot be avoided, the effectiveness of this combination should be carefully monitored during therapy. Antacids; Simultaneously taking a suspension containing magnesium hydroxide and aluminum hydroxide, the concentration of atorvastatin in the plasma decreased about 35%, however, the degree of decrease in the concentration of Xc-LDL did not change.; Phenazone; Atorvastatin does not affect the pharmacokinetics of phenazone; therefore, the interaction ystvie with other drugs metabolized by the same cytochrome, is not expected. Colestipol; In an application colestipol atorvastatin plasma concentration was reduced by about 25%. However, the lipid-lowering effect of the combination of atorvastatin and colestipol exceeded 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 clinical control.; Azithromycin; With simultaneous use of atorvastatin at a dose of 10 mg 1 time / day and azithromycin at a dose of 500 mg 1 time / day, plasma atorvastatin concentrations did not change.; Oral contraceptives; At the simultaneous use of atorvastatin and 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 taken into account when choosing an oral contraceptive for a woman receiving Liprimar.; Terfenadine; With simultaneous use of atorvastatin and terfenadine, no clinically significant changes in the pharmacokinetics of terfenadine were found.; Warfarin; 80 mg / day resulted in a slight increase in prothrombin time by approximately 1.7 s during the first 4 days of therapy. The rate returned to normal within 15 days of atorvastatin therapy.Although significant interactions affecting anticoagulant function were rarely observed, the prothrombin time should be determined before initiating atorvastatin therapy in patients receiving coumarin anticoagulants and often enough during therapy to prevent a significant change in the prothrombin time. Once the prothrombin time stabilizes, it can also be monitored as recommended for patients receiving coumarin anticoagulants. When changing the dose of atorvastatin or discontinuing therapy, monitoring of the prothrombium time should be carried out as described above. Atorvastatin therapy was not associated with the development of bleeding or prothrombin time changes in patients who did not receive anticoagulants.; Colchicine; Although studies of the simultaneous use of colchicine and atorvastatin have not been conducted, myopathy has been reported with this combination. With simultaneous use of atorvastatin and colchicine, caution should be exercised.; Amlodipine; With simultaneous use of atorvastatin at a dose of 80 mg and amlodipine at a dose of 10 mg, the pharmacokinetics of atorvastatin did not change in equilibrium.; Fuzidovaya acid; taking statins simultaneously, including atorvastatin and fusidic acid. The mechanism of this interaction is unknown. In patients for whom the use of fusidic acid is considered necessary, treatment with statins should be discontinued during the entire period of use of fusidic acid. Statin therapy can be resumed 7 days after the last administration of fusidic acid. In exceptional cases, when long-term systemic therapy with fusidic acid is necessary, for example, for the treatment of severe infections, the need for co-administration of atorvastatin and fusidic acid should be considered in each particular case and under strict medical supervision. The patient should immediately seek medical attention if symptoms of muscle weakness, sensitivity or pain appear.; Other concomitant therapy; In clinical studies, Liprimar was used in combination with antihypertensive drugs and estrogens as part of hormone replacement therapy. Symptoms of clinically significant undesirable interactions were noted.Research has also not been conducted with specific drugs. In addition, there was an increase in atorvastatin concentrations while being used with HIV protease inhibitors (a combination of lopinavir and ritonavir, saquinavir and ritonavir, darunavir and ritonavir, fosamprenavir, fosamprenavir with ritonavir, nelfavavir, and injectants; (boceprevir), clarithromycin and itraconazole. Care should be taken with the simultaneous use of these drugs, as well as apply the lowest effective dose of atorvastatin.
special instructions
Effect on the liver; As with the use of other lipid-lowering drugs of this class, with the use of the drug Liprimar noted a moderate increase (more than 3 times compared with VGN) a