Tulip coated pills 40mg N30
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Atorvastatin
Release form
Pills
Composition
1 tab. atorvastatin calcium 41.43 mg, which corresponds to the content of atorvastatin 40 mg. Excipients: microcrystalline cellulose - 284.
Pharmacological effect
Lipid-lowering agent. Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase - an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, which is a precursor of sterols, including cholesterol. Triglycerides (TG) and cholesterol (Xc) are included in very low density lipoproteins (VLDL) during synthesis in the liver, enter the blood plasma and are transported to peripheral tissues. Low density lipoproteins (LDL) are formed from VLDL during interaction with LDL receptors. Studies have shown that increasing the concentration of total XC, LDL and apolipoprotein B (apo-B) in the blood plasma contributes to the development of atherosclerosis and are included in the group of risk factors for cardiovascular diseases, while an increase in the concentration of high-density lipoprotein (HDL) reduces the risk development of cardiovascular diseases. Atorvastatin reduces the concentration of Xc and lipoproteins in the blood plasma by inhibiting HMG-CoA reductase, cholesterol synthesis in the liver and increasing the number of “liver” LDL receptors on the cell surface, which leads to increased uptake and LDL catabolism (according to preclinical studies). Atorvastatin reduces the synthesis and concentration of Xc-LDL, total Xc, apo-B in patients with homozygous and heterozygous familial hypercholesterolemia, primary hypercholesterolemia and mixed hyperlipidemia. It also causes a decrease in the concentration of cholesterol-VLDL and TG and an increase in the concentration of cholesterol-HDL and apolipoprotein A-1 (apo-A). In patients with dysbetalipoproteinemia, decreases the concentration of lipoproteins of intermediate density Xc-Lpp. Atorvastatin in doses of 10 mg and 20 mg reduces the concentration of total cholesterol by 29% and 33%, LDL - by 39% and 43%, apo-B - by 32% and 35% and TG - by 14% and 26%, respectively; causes an increase in cholesterol-HDL and apo-A. Atorvastatin in doses of 40 mg reduces the concentration of total cholesterol by 37%, LDL - by 50%, apo-B - by 42% and TG - by 29%; causes an increase in the concentration of Xc-HDL and apo-A.Dose-dependently reduces the concentration of LDL in patients with homozygous familial hypercholesterolemia resistant to other lipid-lowering drugs. It has no carcinogenic and mutagenic effects. The therapeutic effect develops 2 weeks after the start of therapy, reaches a maximum after 4 weeks and lasts for the entire period of treatment.
Pharmacokinetics
Absorption and distribution: Absorption is high. Cmax in the blood plasma after ingestion is achieved after 1-2 hours. Eating a little reduces the rate and extent of absorption of the drug (by 25% and 9%, respectively), but the decrease in Xc-LDL is similar to that of atorvastatin without simultaneous ingestion of food. After ingestion of atorvastatin in the evening, its plasma concentration is lower (Cmax and AUC by about 30%) than it was taken in the morning, while the decrease in Xc-LDL does not depend on the time of day the drug is taken. A linear relationship was found between the degree of absorption and the dose of the drug. Bioavailability is 12-14%, systemic bioavailability of inhibitory activity against HMG-CoA reductase - about 30%. Low systemic bioavailability due to presystemic metabolism in the gastrointestinal tract and the effect of "first pass" through the liver. Average Vd - 381 l, binding to plasma proteins - 98%. The ratio of atorvastatin concentration in erythrocytes / blood plasma is about 0.25, which indicates poor penetration of atorvastatin into erythrocytes. Metabolism and excretion: Atorvastatin is metabolized mainly in the liver under the action of isoenzymes CYP3A4, CYP3A5 and CYP3A7 with the formation of pharmacologically active metabolites (ortho and parahydroxylated derivatives, beta-oxidation products). In vitro, ortho and parahydroxylated metabolites have an inhibitory effect on HMG-CoA reductase comparable to that of atorvastatin. The inhibitory effect of the drug in relation to HMG-CoA reductase by about 70% is determined by the activity of circulating metabolites, which persists for approximately 20-30 hours, due to their presence. The results of in vitro studies suggest that liver CYP3A4 isoenzyme plays an important role in the metabolism of atorvastatin. This is confirmed by an increase in plasma atorvastatin concentration 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.Excreted mainly through the intestines after hepatic and / or extrahepatic metabolism (the drug is not subjected to severe enterohepatic recirculation). T1 / 2 - 14 hours. T1 / 2 of the inhibitory activity of HMG-CoA reductase is 20-30 hours. Less than 2% of the ingested dose is determined in urine. It is not displayed during hemodialysis due to intense binding to plasma proteins. Pharmacokinetics in special clinical situations: In women, Cmax is higher by 20%, AUC is lower by 10% than in men, which has no clinical significance. In patients with alcoholic cirrhosis (Child-Pugh class B), the liver Cmax is 16 times, and AUC is 11 times higher than normal. Cmax and AUC in elderly patients (65 years) are 40% and 30%, respectively, higher than in young patients, but this does not affect the degree of LDL cholesterol reduction. Impaired renal function does not affect the concentration of the drug in plasma, the degree of lowering LDL cholesterol.
Indications
- in combination with a cholesterol-lowering diet to reduce elevated concentrations of total Xc, Xc-LDL, apo-B and TG and increase the concentration of Xc-HDL in patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolemia and combined (mixed) hyperlipidemia (type IIa) according to the Fredrickson classification), when diet therapy and other non-pharmacological treatment methods are not effective enough to reduce the concentration of total Xc and Xc-LDL in patients with homozygous familial hypercholesterol when diet therapy and other non-pharmacological treatment methods are not effective enough - primary prevention of cardiovascular complications in patients without clinical signs of coronary heart disease, but having several risk factors for its development: age over 55 years old, nicotine dependence, arterial hypertension, diabetes mellitus, retinopathy, albuminuria, low concentrations of HDL-C HDL in the blood plasma, genetic predisposition, including against dyslipidemia - secondary prevention of cardiovascular complications in patients with coronary artery disease in order to reduce the overall mortality rate, myocardial infarction, stroke, re-hospitalization for angina and the need for revascularization.
Contraindications
- liver disease in the active stage or increased activity of hepatic transaminases in the blood plasma (more than 3 times compared to VGN) of unknown origin - pregnancy - lactation period - age up to 18 years (efficacy and safety not established) - lactase deficiency, lactose intolerance ,Glucose-galactose malabsorption syndrome (because the composition contains lactose) - hypersensitivity to atorvastatin and other auxiliary components of the drug. Precautions should be prescribed the drug for alcohol abuse, liver disease in history, muscular system diseases (in history from the use of other members of the HMG-CoA reductase inhibitor group), severe electrolyte imbalance, endocrine (hyperthyroidism) and metabolic disorders, arterial hypotension, sugar diabetes, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical procedures, injuries, aggressive lipid-lowering therapy (atorvastatin 80 mg) n In secondary prevention of stroke in patients with a hemorrhagic or lacunar stroke in history.
Use during pregnancy and lactation
Tulip drug is contraindicated for use during pregnancy. Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of using the drug during pregnancy. If pregnancy is diagnosed during the treatment with Tulip, its reception should be stopped as soon as possible, and the patient should be warned of the potential risk to the fetus. The drug Tulip can be used in women of reproductive age only if the probability of pregnancy is very low and the patient is informed about the possible risk to the fetus during treatment. Women of reproductive age during treatment with Tulip should use reliable methods of contraception. Atorvastatin is excreted in breast milk, therefore it is contraindicated for use during breastfeeding. If necessary, the use of the drug Tulip during lactation breastfeeding should be stopped.
Dosage and administration
Before starting the use of Tulip, the patient should be advised to recommend a standard cholesterol-lowering diet, which he should continue to follow throughout the entire period of drug therapy. The drug is taken orally, regardless of the time of meals.The dose of Tulip varies from 10 mg to 80 mg per day, and is selected based on the initial concentrations of Xc-LDL, the goal of therapy and the individual therapeutic response to the therapy. For most patients, the initial dose is 10 mg 1 time / day. At the beginning of treatment, after 2-4 weeks of therapy and / or after increasing the dose of the drug Tulip, it is necessary to control plasma lipid concentrations and, if necessary, adjust the dose of the drug. The maximum daily dose is 80 mg / day. Primary (heterozygous hereditary and polygenic) hypercholesterolemia (type IIa) and mixed hyperlipidemia (type IIb) In most cases, it is enough to use Tulip at a dose of 10 mg 1 time / day (atorstastatin pills of 10 and 20 mg are possible). If necessary, it is possible to gradually increase the dose to 80 mg (2 tab. 40 mg), depending on the patient's response with an interval of 2-4 weeks, since the therapeutic effect is observed after 2 weeks, and the maximum therapeutic effect - after 4 weeks. With long-term treatment, this effect persists. Homozygous hereditary hypercholesterolemia Tulip preparation in most cases is used in a dose of 80 mg (2 tab. 40 mg) 1 time / day. Prevention of the development of cardiovascular diseases Tulip is used in a dose of 10 mg 1 time / day. If the optimal concentration of LDL in plasma is not reached, an increase in the dose of the drug to 80 mg / day is possible, depending on the response of the patient with an interval of 2-4 weeks. Correction of the dose of the drug Tulip in patients with impaired renal function and in elderly patients is not required. In patients with impaired liver function, the release of atorvastatin from the body is slowed down; therefore, it is recommended to use it with caution while constantly monitoring the activity of hepatic transaminases: ACT and ALT. If the observed increase in the activity of ACT or ALT is more than 3 times compared with VGN is maintained, a dose reduction or withdrawal of the drug Tulip is recommended.
Side effects
According to the WHO, undesirable effects are classified according to their development frequency as follows: often (> 1/100, less than 1/10), infrequently (> 1/1000, less than 1/100), rarely (> 1/10 000, less than 1/100 ) and very rarely (less than 1/10 000), including individual messages; frequency is unknown - according to the available data it was not possible to establish the frequency of occurrence. On the part of the immune system: often - allergic reactions; very rarely - anaphylaxis.From the nervous system: often - headache; infrequently - dizziness, sleep disturbances, including insomnia and nightmares, asthenic syndrome, weakness, paresthesia, hypoesthesia, taste disturbance, loss or loss of memory; rarely, peripheral neuropathy. From the senses: infrequently - tinnitus, blurred vision; rarely - visual impairment; very rarely - hearing loss. On the part of the digestive system: often - constipation, flatulence, dyspepsia, nausea, diarrhea; infrequently - anorexia, vomiting, pancreatitis, hepatitis, abdominal pain, belching; rarely - cholestatic jaundice (including obstructive); very rarely - liver failure. On the part of the musculoskeletal system: often - myalgia, arthralgia, swelling of the joints, pain in the joints, back pain, muscle spasm; infrequently - pain in the muscles of the neck, muscle weakness; rarely - myopathy, myositis, rhabdomyolysis, tendinopathy (sometimes complicated by tendon rupture); frequency unknown - immuno-mediated necrotizing myopathy. On the part of the skin and subcutaneous tissues: infrequently - urticaria, skin rash and itching, alopecia; rarely - angioedema, bullous rash, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome). Metabolism: often - hyperglycemia; infrequently - hypoglycemia. From the hemopoietic system: infrequently - thrombocytopenia. On the part of the respiratory system: often - nasopharyngitis, sore throat, nosebleeds. Laboratory indicators: often - increased activity of serum CPK, increased activity of hepatic transaminases; infrequently - leukocyturia; unknown frequency - increased concentration of glycosylated hemoglobin. Other: infrequently - fatigue, impaired potency, secondary renal failure, fever, chest pain, peripheral edema, weight gain; very rarely - gynecomastia, diabetes. There are separate reports on the development of atonic fasciitis (the association with the use of atorvastatin has not been established exactly); frequency is unknown - depression, interstitial lung disease (especially with long-term therapy), sexual dysfunction.
Overdose
Treatment: there is no specific antidote for the treatment of overdose.In case of overdose, symptomatic treatment should be carried out. Hemodialysis is not effective (because the drug is significantly associated with plasma proteins).
Interaction with other drugs
The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases with simultaneous use with cyclosporine, erythromycin, clarithromycin, immunosuppressive, antifungal drugs (azole derivatives) due to a possible increase in serum levels of atorvastatin. When used simultaneously with HIV protease inhibitors - indinavir, ritonavir - increases the risk of myopathy. A similar interaction is possible with simultaneous use of atorvastatin with fibrates and nicotinic acid in lipid-lowering doses (more than 1 g / day). CYP3A4 isoenzyme inhibitors. Since atorvastatin is metabolized by the CYP3A4 isoenzyme, co-administration of Tulip with inhibitors of this isoenzyme can lead to an increase in plasma atorvastatin concentration. The degree of interaction and the effect of increasing the concentration of atorvastatin are determined by the variability of exposure to the CYP3A4 isoenzyme. 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 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 7.7 times. Erythromycin / clarithromycin With simultaneous use of atorvastatin 10 mg and erythromycin (500 mg 4 times / day) or clarithromycin (500 mg 2 times / day), which inhibit the cytochrome CYP3A4 isoenzyme, an increase in atorvastatin plasma levels (40% - when used with erythromycin and 56% when used with clarithromycin). Protease Inhibitors Simultaneous use of atorvastatin with protease inhibitors, known as inhibitors of the cytochrome CYP3A4 isoenzyme, is accompanied by an increase in plasma atorvastatin concentration (with simultaneous use with erythromycin — Cmax 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 of 20 mg to 40 mg and itraconazole at a dose of 200 mg leads to a 3-fold increase in the AUC value of atorvastatin. Grapefruit Juice Because grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme, its excessive use (more than 1.2 liters per day for 5 days) can cause an increase in plasma atorvastatin concentrations. CYP3A4 isoenzyme inducers Combined use of atorvastatin with inducers of isoenzyme SURZA4 (for example, efavirenz or rifampicin) can lead to a decrease in plasma atorvastatin concentration. Due to the dual mechanism of interaction with rifampicin (CYP3A4 isoenzyme inducer and hepatocyte transport protein inhibitor OATP1B1), simultaneous use of atorvastatin and rifampicin is not recommended, since delayed atorvastatin administration after taking rifampicin leads to a significant decrease in atorvastatin concentration in the blood plasma. Antacids With simultaneous oral administration of atorvastatin and a suspension containing magnesium and aluminum hydroxides, plasma concentration of atorvastatin decreases by approximately 35%, however, the degree of decrease in the concentration of Xc-LDL does not change. Phenazone Atorvastatin does not affect the pharmacokinetics of phenazone, so interaction with other drugs metabolized by the same isoenzymes is not expected. Colestipol The hypolipidemic effect of a combination with colestipol is greater than that for each drug separately, despite a decrease in the concentration of atorvastatin by 25% when used simultaneously with colestipol. Fuzidovoy acid Research on the interaction of atorvastatin and fusidic acid was not conducted. As with other statins, post-marketing studies of the combined use of atorvastatin and fusidic acid reported side effects on the muscles, including rhabdomyolysis. The mechanism of interaction is unknown. Such patients require careful monitoring and, possibly, temporary discontinuation of atorvastatin. Colchicine Although atorvastatin and colchicine have not been studied, myopathy has been reported when used together with colchicine, and when atorvastatin and colchicine are given at the same time, caution should be exercised. Digoxin When repeated use of digoxin and atorvastatin in a dose of 10 mg Css of digoxin in the blood plasma does not change.However, when using digoxin in combination with atorvastatin at a dose of 80 mg / day, the concentration of digoxin in the blood plasma increases by about 20%. Patients taking digoxin in combination with atorvastatin require control of the concentration of digoxin in the blood plasma. Azithromycin With simultaneous use of atorvastatin in a dose of 10 mg 1 time / day and azithromycin in a dose of 500 mg 1 time / day, the concentration of atorvastatin in the blood plasma does not change. Oral contraceptives With simultaneous use of atorvastatin and oral contraceptives containing norethisterone and ethinyl estradiol, there is a significant increase in the AUC of norethisterone and ethinyl estradiol by about 30% and 20%, respectively, which should be considered when choosing an oral contraceptive. Terfenadine Atorvastatin with simultaneous use with terfenadine does not have a clinically significant effect on the pharmacokinetics of terfenadine. Warfarin In patients who take warfarin for a long time, atorvastatin at a dose of 80 mg / day shortens the prothrombin time somewhat in the first days of combined use. This effect disappears after 15 days of simultaneous use of these drugs. Although cases of clinically significant changes in the anticoagulant effect were reported very rarely, prothrombin time should be measured in patients taking coumarin anticoagulants before and, often enough, at the beginning of treatment with atorvastatin, to ensure that there are no significant changes in the prothrombin time. As soon as a stable prothrombin time is recorded, it can be checked at intervals usual for patients taking coumarin anticoagulants. When changing the dose or discontinuation of treatment, these measures should be repeated. There was no association between atorvastatin use and bleeding or a change in prothrombin time in patients not taking anticoagulants. Amlodipine With simultaneous use of atorvastatin at a dose of 80 mg and amlodipine at a dose of 10 mg, the pharmacokinetics of atorvastatin does not change in the equilibrium state. Other lipid-lowering drugs With simultaneous use of atorvastatin with other lipid-lowering drugs (for example, ezetimibe, gemfibrozil,fibric acid derivative) in lipid-lowering doses increases the risk of rhabdomyolysis. Other concomitant therapy With the simultaneous use of atorvastatin with antihypertensives and estrogens (as a replacement therapy), no clinically significant interaction has been identified.
special instructions
Effect on the liver As with the use of other HMG-Co-reductase inhibitors (statins), with Tulip therapy, there may be a moderate (more than 3-fold increase compared to VGN) increased serum activity of hepatic transaminases: ACT and ALT. Before starting therapy, after 6 weeks and 12 weeks after starting taking Tulip or after increasing its dose, it is necessary to monitor indicators of liver function (ACT, ALT). Liver function should also be monitored when clinical signs of liver damage appear. In the case of increased activity of ACT and ALT, their activity should be monitored until it normalizes. Tulip should be used with caution in patients who abuse alcohol and / or have a history of liver disease. Diseases of the liver in the active stage or increased activity of hepatic transaminases of blood plasma of unknown origin are a contraindication to the use of the drug Tulip. Stroke prevention with intensive lipid-lowering therapy (SPARCL) In a retrospective analysis of various types of stroke in people not suffering from coronary heart disease who recently had a stroke or transient ischemic attack (TIA), a higher risk of hemorrhagic stroke was seen in patients taking stroke. mg versus placebo. Especially high risk was observed in patients who had hemorrhagic stroke or lacunar infarction at the time of the study. For patients who have had a hemorrhagic stroke or lacunar infarction and are taking atorvastatin at a dose of 80 mg, the risk / benefit ratio is ambiguous, and the potential risk of hemorrhagic stroke should be carefully assessed before starting treatment. Effect on skeletal muscles When using the drug Tulip may develop myalgia. The diagnosis of myopathy (pain and weakness in the muscles in combination with an increase in the activity of CPK more than 10 times compared with VGN) may be suggested in patients with diffuse myalgia, muscle soreness or weakness and / or a pronounced increase in the activity of CPK.Therapy with Tulip should be stopped in case of a pronounced increase in the activity of CPK or in the presence of confirmed or suspected myopathy. The use of other HMG-Co-reductase inhibitors (statins) may increase the risk of myopathy while using it with cyclosporine, fibrates, erythromycin, nicotinic acid in lipid-lowering doses (more than 1 g / day) or antifungal drugs of the azoles group. When using Tulip in combination with fibrates, erythromycin, immunosuppressants, antifungals of the azoles group or nicotinic acid in lipid-lowering doses (more than 1 g / day), it is necessary to weigh the expected benefits and risks of treatment with Tulip. Very rarely, cases of immune-mediated necrotizing myopathy have been reported during or after treatment with statins, including atorvastatin. Immune-mediated necrotizing myopathy is clinically characterized by muscle weakness in the upper limbs and an increase in plasma CK concentration, which persists despite discontinuation of treatment with statins. If necessary, combination therapy should consider the possibility of using these drugs in lower initial and maintenance doses. Periodic monitoring of CPK activity is recommended. The combined use of atorvastatin and fusidic acid is not recommended, therefore, should be considered a temporary cessation of therapy with atorvastatin during the use of fusidic acid. Patients should be warned that they should immediately consult a doctor if they develop unexplained pain or muscle weakness, especially if they are accompanied by indisposition or fever. When using the drug Tulip, as well as other HMG-Co-reductase inhibitors (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 in the presence of rhabdomyolysis (for example, severe acute infection, arterial hypotension, extensive surgical intervention, injuries, serious metabolic, electrolyte and endocrine disorders and uncontrolled seizures), Tulip should be stopped or completely canceled .Interstitial lung disease Extremely rare cases of interstitial lung disease have been reported with some statins, especially with long-term therapy. Clinical manifestations include shortness of breath, unproductive cough, and worsening of general health (fatigue, weight loss, and fever). If interstitial lung disease is suspected, statin treatment should be discontinued. Diabetes mellitus Some studies have shown that the use of statins as a class may lead to an increase in blood glucose concentration, and in some patients with an increased risk of developing diabetes in the future may cause hyperglycemia, which requires standard antidiabetic therapy. However, this risk is insignificant compared with a decrease in vascular risk when taking statins, and, therefore, should not be a cause of discontinuation of treatment with statins. Patients at risk (with a fasting glucose concentration of 5.6-6.9 mmol / l, BMI> 30 kg / m2, elevated triglycerides, elevated blood pressure) should be controlled, both clinical and biochemical, in accordance with national standards of care . Impact on the ability to drive motor vehicles and control mechanisms During the period of treatment with Tulip, care must be taken when driving and engaging in other potentially hazardous activities that require increased concentration and psychomotor speed.