Tevastor pills 20 mg 30 pcs
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Active ingredients
Rosuvastatin
Release form
Pills
Composition
Rosuvastatin calcium 20.83 mg; which corresponds to the content of rosuvastatin 20 mg; auxiliary substances: microcrystalline cellulose - 90.45 mg, crospovidone - 60 mg, lactose - 104.72 mg, povidone-K30 - 17 mg, sodium stearyl fumarate - 7 mg; shell composition: opadry ii 85f24155 pink (polyvinyl alcohol partially hydrolyzed - 3.6 mg, titanium dioxide (e171) - 2.21 mg, macrogol-3350 - 1.818 mg, talc - 1.332 mg, iron dye yellow oxide (e172) - 0.018 mg, iron dye red oxide (e172) - 0.01 mg, dye Azorubine aluminum varnish (e122) - 0.009 mg, indigo carmine aluminum varnish (e132) - 0.003 mg).
Pharmacological effect
A lipid-lowering drug, a selective competitive inhibitor of HMG-CoA reductase - an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, a precursor of cholesterol (CH). The main target of rosuvastatin is the liver, where Xc synthesis and LDL catabolism are performed. Rosuvastatin increases the number of “liver” LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of VLDL, thereby reducing the total number of LDL and VLDL. Rosuvastatin reduces the increased concentration of Xc-LDL, total cholesterol, TG, increases the concentration of Xc-HDL, as well as reduces the concentration of apolipoprotein B (ApoB), Xc-non-LPVP, Xc-VLDL, TG-VLDL and increases the concentration of apolipoprotein A-1 (ApoA) 1), reduces the ratio of Xc-LDL / Xc-HDL, total Xc / Xc-HDL and Xc-non-LPVP / Xc-HDL and the ratio of ApoB / ApoA-1.; The therapeutic effect appears within 1 week after the start of therapy with rosuvastanin, after 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by week 4 and is maintained with regular intake.
Pharmacokinetics
Absorption; Cmax of rosuvastatin in the blood plasma is reached approximately 5 hours after ingestion. Absolute bioavailability - approximately 20%; Distribution; Plasma protein binding (predominantly with albumin) is approximately 90%. Rosuvastatin accumulates mainly in the liver - the main organ of the synthesis of Xc and clearance of Xc-LDL. Vd - about 134 l.; Metabolism; Biotransforming to a small extent (about 10%), being a non-core substrate for metabolism by enzymes of the cytochrome P450 system. CYP2C9 is the main isoenzyme involved in rosuvastatin metabolism.CYP2C19, CYP3A4, and CYP2D6 isoenzymes are less involved in metabolism. The main identified metabolites of rosuvastatin are N-dismethyl and lactone metabolites. N-dismethyl is about 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity on inhibition of circulating HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites.; Excretion; T1 / 2 - approximately 19 hours. T1 / 2 does not change with increasing dose of the drug. About 90% of the dose of rosuvastatin is excreted unchanged with feces. The rest is excreted in the urine. The average value of plasma clearance is approximately 50 l / h (coefficient of variation - 21.7%). As in the case of other HMG-CoA redaction inhibitors, the hepatic capture of rosuvastatin involves membrane anion transporter Xc, which plays an important role in the hepatic elimination of rosuvastatin; Pharmacokinetics in particular clinical cases; Rosuvastatin.; In patients with mild and moderately severe renal insufficiency, the plasma concentration of rosuvastatin or N-dismethyl does not change significantly. Patients with severe renal insufficiency (CC less than 30 ml / min) plasma concentration of rosuvastatin is 3 times higher, and N-dismethyl concentration is 9 times higher than in healthy volunteers; plasma concentration of rosuvastatin was hemodialysis about 50% higher than in healthy volunteers.; Patients with different stages of liver failure (score 7 and below on the Child-Pugh scale) did not show an increase in T1 / 2 of rosuvastatin. In 2 patients with grades 8 and 9 on the Child-Pugh scale, an increase in T1 / 2 was noted at least 2 times. Experience with rosuvastatin in patients with a score higher than 9 on the Child-Pugh scale is absent. Comparative studies of rosuvastatin pharmacokinetics in Japanese and Chinese patients living in Asia showed an approximately twofold increase in AUC values compared with Europeans living in Europe and Asia No influence of genetic and environmental factors on the differences in pharmacokinetic parameters was revealed.A pharmacokinetic analysis among different ethnic groups of patients did not reveal clinically significant differences among Europeans, Hispanics, blacks or African Americans.
Indications
- primary hypercholesterolemia or mixed hypercholesterolemia (type IIb according to Fredrikson) - as a supplement to the diet, when diet and other non-drug methods of treatment (for example, exercise, weight loss) are insufficient; - familial homozygous hypercholesterolemia - as a supplement to the diet and other lipid-lowering therapy, or in cases when such therapy is not sufficiently effective; - hypertriglyceridemia (type IV according to Fredrickson) as a supplement to the diet; - to slow the progression of atherosclerosis as a supplement to the diet in patients who have been shown therapy to reduce the concentration of total Xc and Xc-LDL; - primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary artery disease, but with an increased risk of its development (age over 50 years for men and over 60 years for women, increased concentration of C-reactive protein (at least 2 mg / l) in the presence of at least one of the additional risk factors, such as hypertension, low concentrations of HD-C, HDL, smoking, a family history of early onset of CHD).
Contraindications
For pills 5, 10 and 20 mg; - liver disease in the active phase, including a persistent increase in the activity of hepatic transaminases or any increase in the activity of hepatic transaminases (more than 3 times as compared with VGN); - severe violations of the liver (more than 9 points on the Child-Pugh scale) (there is no experience of use); - severe renal dysfunction (CC less than 30 ml / min); - myopathy; - simultaneous administration of cyclosporine; - pregnancy; - breastfeeding period; - lack of reliable methods of contraception; - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose); - age up to 18 years (not enough data on efficiency and safety); - hypersensitivity to the components of the drug.; For pills 40 mg; - liver disease in the active phase, including a persistent increase in liver transaminases and any increase in liver transaminases(more than 3 times compared with VGN); - simultaneous reception of fibrates; severe violations of the liver (more than 9 points on the Child-Pugh scale) (no experience with the application); - patients with risk factors for myopathy / rhabdomyolysis: renal failure (QC less than 60 ml / min), hypothyroidism, personal or family analysis of muscular diseases, myotoxicity while taking other HMG-Co-A reductase inhibitors or fibrates in history; excessive drinking; conditions that can lead to increased plasma concentrations of rosuvastatin; - simultaneous administration of cyclosporine; - pregnancy; - breastfeeding period; - lack of reliable methods of contraception; - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose); - age up to 18 years (not enough data on efficiency and safety); - use in patients of the Asian race; - hypersensitivity to the components of the drug.; With caution; For pills 5, 10 and 20 mg: the presence of risk factors for the development of myopathy and / or rhabdomyolysis - renal failure, hypothyroidism, personal or family analysis of hereditary muscular diseases and previous history of muscular toxicity when using other HMG-Co-A reductase inhibitors or fibrates; excessive alcohol consumption, age over 65 years, conditions in which there is an increase in the plasma concentration of rosuvastatin; race (Asian race), simultaneous use with fibrates, history of liver disease, sepsis, arterial hypotension, extensive surgery, trauma, severe metabolic, endocrine or electrolyte disturbances, or uncontrolled seizures. For pills 40 mg: renal failure (QC) more than 60 ml / min), over 65 years of age, history of liver disease, sepsis, hypotension, extensive surgery, trauma, severe metabolic, endocrine or electrolysis tnye disorders or uncontrolled seizures.
Use during pregnancy and lactation
Tevastor is contraindicated during pregnancy and during breastfeeding. When diagnosing pregnancy in the course of therapy, the drug should be stopped immediately. Women of reproductive age should use reliable methods of contraception.Since cholesterol and its biosynthesis products are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase exceeds the benefit of using the drug. There are no data on the release of rosuvastatin into breast milk, so if you need to use Tevastor during lactation, breastfeeding should be stopped.
Dosage and administration
The drug is taken orally at any time of the day, regardless of the meal. The tablet should be swallowed whole, washed down with water, not chewed or crushed. If you need to take the drug in a dose of 5 mg, you should divide the tablet of 10 mg in half.; Before starting therapy with Tevastor, the patient should begin to follow a standard lipid-lowering diet and continue to follow it during treatment. taking into account current recommendations on target lipid levels.; The recommended starting dose of Tevastor for patients starting a drug or for patients transferred from Receiving other inhibitors of HMG-CoA reductase inhibitor is 5 or 10 mg of 1 time / day. When choosing the initial dose, one should be guided by the patient’s cholesterol content and take into account the risk of cardiovascular complications, and the potential risk of side effects should be assessed. If necessary, the dose may be increased after 4 weeks.; Patients with severe hypercholesterolemia and with a high risk of cardiovascular complications (especially patients with familial hypercholesterolemia) who have not achieved the desired result when taking a dose of 20 mg for 4 weeks therapy, with an increase in the dose of the drug to 40 mg should be under the supervision of a physician in connection with a possible increased risk of side effects. Especially careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. After 2-4 weeks of therapy and / or increasing the dose of Tevastor, monitoring of lipid metabolism indices is necessary. In elderly patients (over 65 years of age), it is recommended to start treatment with a dose of 5 mg. Mild to moderate doses in patients with renal failure do not required.The use of the drug Tevastor in any doses for severe renal failure (CC less than 30 ml / min) is contraindicated. The use of the drug Tevastor in a dose of 40 mg in patients with moderate renal impairment (CC less than 60 ml / min) is contraindicated. An initial dose of 5 mg is recommended for patients with moderately impaired renal function. For patients of the Asian race, the recommended initial dose is 5 mg. The use of the drug Tevastor in a dose of 40 mg in patients of the Asian race is contraindicated. The administration of the drug Tevastor in a dose of 40 mg in patients with factors that may indicate a predisposition to the development of myopathy is contraindicated. When prescribing the drug in doses of 10 mg and 20 mg, an initial dose is recommended for patients in this group of 5 mg. In carriers of the SLCO1B1 (OATP1B1) genotypes c.521CC and ABCG2 (BCRP) c.421AA, there was an increase in exposure (AUC) to rosuvastatin compared to carriers of the SLCO1B1 genotypes c.521TT and ABCG2c.421CC.For patients carrying the c.521CC or c.421AA genotypes, the recommended maximum daily dose of Tevastor is 20 mg 1 time / day (see the sections "Pharmacokinetics", "Special instructions" and " Interaction with other drugs "); simultaneous use of Tevastor with cyclosporine and HIV protease inhibitors (including the combination of ritonavir with atazanavir, lopinavir) increases the risk of myopathy (including rhabdomyolysis), so you should consider the possibility of alternative therapy or temporary discontinuation of Tevastor. In case of simultaneous use of these drugs is inevitable, the ratio of benefits / risks of concomitant therapy with Tevastor should be evaluated and the possibility of reducing its dose.
Side effects
Side effects observed with the use of the drug Tevastor, usually expressed slightly and pass on their own. As with the use of other inhibitors of HMG-CoA reductase, the frequency of side effects is mainly dose-dependent. Determination of the frequency of side effects: often (more than 1/100, less than 1/10), infrequently (more than 1/1000, less than 1/100) , rarely (more than 1/10 000, less than 1/1000); very rarely (less than 1/10 000), unknown frequency (cannot be calculated according to the available data); From the immune system: rarely - hypersensitivity reactions, including angioedema; From the endocrine system: often - type 2 diabetes. ; CNS: often - headache,dizziness. From the digestive system: often - constipation, nausea, abdominal pain; rarely - pancreatitis.; On the part of the skin: infrequently - pruritus, rash, urticaria.; On the part of the musculoskeletal system: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis. When using the drug Tevastor in all doses, especially in doses of more than 20 mg - myalgia, myopathy (including myositis); in rare cases, rhabdomyolysis with or without acute renal failure. A dose-dependent increase in CPK activity is observed in a small number of patients taking rosuvastatin. In most cases, the increase in CPK activity was insignificant, asymptomatic, and transient. In case of increased CPK activity (more than 5 times as compared with VGN), rosuvastatin therapy should be suspended. From the urinary system: proteinuria can be detected in patients receiving Tevastor. Changes in the amount of protein in the urine (from the absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving the drug in a dose of 10-20 mg, and in about 3% of patients receiving the drug in a dose of 40 mg. In most cases, proteinuria diminishes or disappears during therapy and does not mean the onset or acute progression of existing kidney disease. From the liver: a dose-dependent increase in liver transaminase activity in a small number of patients. In most cases, it is insignificant, asymptomatic and temporary. From the laboratory indicators: an increase in the concentration of glucose, bilirubin, activity of GGT, ALP, thyroid gland dysfunction.; Others: often - asthenic syndrome; : unspecified frequency - thrombocytopenia. On the part of the digestive system: rarely - increased activity of hepatic transaminases; very rarely - jaundice, hepatitis; unspecified frequency - diarrhea. From the musculoskeletal system: very rarely - arthralgia; unspecified frequency - immune-mediated necrotizing myopathy.; CNS: very rarely - polyneuropathy, memory loss.; On the part of the respiratory system: unspecified frequency - cough, shortness of breath;; Urinary system: very rarely - hematuria.; subcutaneous fat: unspecifiedfrequency - Stevens-Johnson syndrome. From the reproductive system: unspecified frequency - gynecomastia.; Other: unspecified frequency - peripheral edema.; When using certain statins, the following side effects were reported: depression, sleep disorders (including insomnia, "nightmare" dreams), sexual dysfunction. It was reported on isolated cases, interstitial lung disease, especially with prolonged use of drugs.
Overdose
With simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change. Treatment: with an overdose, if necessary, symptomatic therapy is carried out, monitoring of liver function and CPK activity is necessary. There is no specific antidote. Hemodialysis is not effective.
Interaction with other drugs
With the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than that observed in healthy volunteers, while the plasma concentration of cyclosporine did not change. Start of therapy with rosuvastatin or increase the dose of the drug in patients receiving vitamin K antagonists at the same time (for example, warfarin), may result in an increase in the International Normalized Relationship (MHO). Canceling rosuvastatin or reducing its dose can lead to a decrease in MHO (monitoring of MHO is recommended in such cases); Simultaneous use of rosuvastatin at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in AUC of rosuvastatin in patients with hypercholesterolemia. due to the pharmacodynamic interaction between rosuvastatin and ezetimibe.; The simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase Cmax in plasma and AUC of rosuvastatin. According to special studies, the corresponding pharmacokinetic interaction with fenofibrate is not observed, but pharmacodynamic interaction is possible. Hemofibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increase the risk of myopathy when used concurrently with HMG-CoA reductase inhibitors (probably due to the fact that HMG-CoA inhibitors can cause myopathy and when used as monotherapy) Although the exact mechanism of interaction of rosuvastatin with protease inhibitors is unknown, their simultaneous use may cause a sustained increase in the effect of rosuvastatin.In pharmacokinetic studies in healthy volunteers, the combined use of 20 mg of rosuvastatin and a combination of protease inhibitors (lopinavir 400 mg / ritonavir 100 mg) caused an approximately 2- and 5-fold increase in AUC and Cmax, respectively. Therefore, the simultaneous use of rosuvastatin and protease inhibitors in the treatment of patients with HIV is not recommended.; The simultaneous use of rosuvastatin and suspensions of antacids containing aluminum and magnesium hydroxide, reduces the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied. The simultaneous use of rosuvastatin and erythromycin reduces the AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%, probably as a result of increased intestinal motility caused by taking erythromycin. and AUC norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be considered when selecting the dose of oral contraceptives against the background of rosuvastatin.; Based on studies of the interaction of rosuvastatin with digoxin, no clinically significant interaction was found.; The results of in vivo and in vitro studies showed that rosuvastatin is neither an inhibitor nor an isoenzyme inducer cytochrome P450 systems. In addition, rosuvastatin is a weak substrate for these isoenzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4). Thus, interactions associated with the cytochrome P450 system are not expected.
special instructions
Proteinuria, mostly of renal origin, detected as a result of testing, is observed in patients taking rosuvastatin at a dose of 40 mg and higher, and in most cases is transient. Such proteinuria is not a symptom of acute or progressive renal pathology. The total number of cases of serious renal complications is observed when using rosuvastatin in a dose of 40 mg. When using the drug Tevastor at a dose of 40 mg, it is recommended to monitor indicators of renal function. The effect on skeletal muscles (myalgia, myopathy and very rarely rhabdomyolysis) is observed in patients taking the drug Tevastor, in particular, in a dose of more than 20 mg.Very rare cases of rhabdomyolysis have been reported with ezetimibe with HMG-CoA reductase inhibitors. The likelihood of developing rhabdomyolysis, both when using rosuvastatin and other HMG-CoA reductase inhibitors, is higher at a dose of 40 mg; Determination of CPK activity should not be performed after intense exercise or if there are other possible causes of increased CPK activity obtained results. If the initial activity of CPK is significantly increased (5 times higher than VGN), then in 5-7 days it is necessary to re-measure. You should not begin therapy if the repeated test confirms the initial activity of CPK (5 times higher than VGN); Patients should be warned about the need to immediately inform the doctor if new, previously unnoticed symptoms, unexplained muscle pain, weakness or seizures, especially combined with fever, appear and malaise. Therapy should be discontinued if the activity of CPK is 5 times higher than VGN or in the presence of serious muscular symptoms causing permanent discomfort. With the disappearance of symptoms and the normalization of the activity of CPK, it is necessary to consider the issue of repeated use of rosuvastatin with a minimum dose and careful monitoring. Routine monitoring of CPK activity in the absence of symptoms is impractical. We recommend performing functional diagnostics of the liver before and within 3 months after initiation of therapy.; Impact on ability to drive vehicles and control mechanisms; Studies aimed at studying the effect of Tevastor on driving ability and work with the technique was not carried out. At use of drug Tevastor it is necessary to be careful in connection with the fact that development of dizziness is possible.