Tevastor pills 10 mg 90 pcs
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Active ingredients
Rosuvastatin
Release form
Pills
Composition
1 tab. Rosuvastatin calcium 10.42 mg, which corresponds to the content of rosuvastatin 10 mg. Excipients: microcrystalline cellulose - 45.
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 starting rosuvastanin therapy, after 2 weeks of treatment it 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 is approximately 20%. Distribution: Plasma protein binding (mainly 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 liters. Metabolism: It is biotransformed to a small extent (about 10%), being a non-core substrate for metabolism by cytochrome P450 enzymes. 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. Withdrawal: T1 / 2 - approximately 19 hours. T1 / 2 does not change with an increase in the 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 plasma clearance is approximately 50 l / h (coefficient of variation - 21.7%). As in the case of other inhibitors of HMG-CoA redaction, the hepatic capture of rosuvastatin involves membrane anion carrier Xc, which plays an important role in the hepatic elimination of rosuvastatin. Pharmacokinetics in special clinical situations: Gender and age do not have a clinically significant effect on rosuvastatin pharmacokinetics. In patients with mild and moderate renal insufficiency, the plasma concentration of rosuvastatin or N-dismethyl does not change significantly. In patients with severe renal insufficiency (CC is 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. The plasma concentration of rosuvastatin in hemodialysis patients was 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 above 9 on the Child-Pugh scale is absent. A comparative study of the pharmacokinetics of rosuvastatin in Japanese and Chinese patients living in Asia showed an approximately twofold increase in the mean 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 Fredrickson) - as a supplement to the diet,when diet and other non-drug therapies (such as exercise, weight loss) are insufficient — familial homozygous hypercholesterolemia — as an adjunct to diet and other lipid-lowering therapy, or in cases when such therapy is not effective enough — hypertriglyceridemia (type IV by 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 c-LDL - primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of CHD, but with an increased risk of its development (age over 50 years for men and over 60 years for women, elevated concentration C -reactive protein (at least 2 mg / l) in the presence of at least one of the additional risk factors, such as hypertension, low concentration of HDL-C, smoking, 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 liver transaminase activity or any increase in liver transaminase activity (more than 3 times compared to VGN) - severe abnormal liver function (more than 9 points on the Child - Drink) (no experience) - severe renal dysfunction (CC less than 30 ml / min) - myopathy - simultaneous use of cyclosporine - pregnancy - breastfeeding period - lack of reliable contraception methods - lactose intolerance, deficiency lactase or glucose-galactose malabsorption (the drug contains lactose) - age up to 18 years (not enough data on efficacy and safety) - hypersensitivity to the components of the drug. For 40 mg pills, liver disease in the active phase, including a persistent increase in liver transaminase activity and any increase in liver transaminase activity (more than 3 times compared to VGN) - simultaneous use of fibrate severe liver dysfunction (more than 9 points on the Child-Pugh scale ) (no experience of use) - patients with risk factors for myopathy / rhabdomyolysis: renal failure (CC 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 the history of excessive alcohol use, which can lead to an increase in plasma concentration of rosuvastatin - simultaneous cyclosporine intake - pregnancy - breastfeeding period - lack of reliable methods of contraction - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose) - age up to 18 years (not enough data about efficacy 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 myopathy and / or rhabdomyolysis - renal failure, hypothyroidism, personal or family analysis of hereditary muscular diseases and a previous history of muscle toxicity when using other HMG-Co-A reductase inhibitors or fibrate excess alcohol consumption, age over 65 years, conditions in which there is an increase in plasma concentration of rosuvastatin racial affiliation (Asian race), simultaneous use with fibrates, sick Ia a history of liver, sepsis, hypotension, extensive surgery, trauma, severe metabolic, endocrine or electrolyte disorders, 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 surgical interventions, injuries, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures.
Use during pregnancy and lactation
Tevastor is contraindicated during pregnancy and during breastfeeding. When diagnosing pregnancy during therapy, the drug should be discontinued immediately. Women of reproductive age should use reliable methods of contraception. Since cholesterol and its biosynthesis products are important for fetal development, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of the drug.There is no data on the release of rosuvastatin into breast milk, so if you need to use the drug 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 necessary, taking the drug in a dose of 5 mg should be divided into a tablet of 10 mg in half. Before starting therapy with Tevastor, the patient should begin to follow the standard lipid-lowering diet and continue to follow it during treatment. The dose of the drug should be selected individually depending on the indications and therapeutic response, taking into account the current recommendations on target lipid levels. The recommended initial dose of Tevastor for patients starting the drug, or for patients transferred from receiving other HMG-CoA reductase inhibitors, is 5 or 10 mg 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, after 4 weeks the dose may be increased. 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 during 4 weeks of therapy should be under increased doses of the drug to 40 mg. medical supervision due to the possible increase in the 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, control of lipid metabolism indices is necessary. In elderly patients (over 65 years), it is recommended to begin treatment with a dose of 5 mg. Patients with renal insufficiency of mild or moderate severity dose adjustment is 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. Patients with moderate renal impairment are recommended an initial dose of 5 mg. For Asian patients, the recommended starting 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 prescription 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) c.521CC and ABCG2 (BCRP) c.421AA genotypes, there was an increase in exposure (AUC) to rosuvastatin compared to carriers of the SLCO1B1 genotypes c.521TT and ABCG2c.421CC. .421AA The recommended maximum daily dose of Tevastor is 20 mg 1 time / day (see the Pharmacokinetics, Special Instructions, and Drug Interactions sections). With simultaneous use of the drug 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 the drug Tevastor. If simultaneous use of these drugs is inevitable , the benefit / risk ratio of concomitant therapy with Tevastor should be evaluated and considered l 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 incidence of side effects is mostly dose-dependent. Determination of the frequency of side effects: often (> 1/100, less than 1/10), infrequently (> 1/1000, less than 1/100), rarely (> 1/10 000, less than 1/1000); very rarely (less than 1/10 000), unknown frequency (cannot be calculated from the available data). On the part of the immune system: rarely - hypersensitivity reactions, including angioedema.On the part of the endocrine system: often - type 2 diabetes. From the side of the central nervous system: often - headache, dizziness. On the part of the digestive system: often - constipation, nausea, abdominal pain; rarely - pancreatitis. On the part of the skin: infrequently - itching, rash, hives. From 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 the case of increased activity of CPK (more than 5 times as compared with VGN), rosuvastatin therapy should be suspended. On the part of the urinary system: in patients treated with Tevastor, proteinuria can be detected. 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 the progression of an existing kidney disease. On the part of the liver: a dose-dependent increase in the activity of hepatic transaminases 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, the activity of GGT, ALP, thyroid gland dysfunction. Other: often - asthenic syndrome. Post-marketing use From the side of blood and lymphatic system: 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. From the side of the central nervous system: very rarely - polyneuropathy, memory loss. On the part of the respiratory system: unspecified frequency - cough, shortness of breath.From the urinary system: very rarely - hematuria. On the part of the skin and subcutaneous fat: unspecified frequency - Stevens-Johnson syndrome. Reproductive system disorders: unspecified frequency - gynecomastia. Other: unspecified frequency - peripheral edema. When using some statins, the following side effects were reported: depression, sleep disturbances (including insomnia, "nightmarish" dreams), sexual dysfunction. It was reported on isolated cases, interstitial lung disease, especially with prolonged use of drugs.
Overdose
When several daily doses are taken simultaneously, the pharmacokinetic parameters of rosuvastatin do not change. Treatment: in case of 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 cyclosporin did not change. Initiation of rosuvastatin therapy or an increase in the dose of the drug in patients receiving vitamin K antagonists (for example, warfarin) at the same time can lead to an increase in the International Normalized Relationship (MHO). Canceling rosuvastatin or reducing its dose may lead to a decrease in MHO (in such cases, monitoring of MHO is recommended). The simultaneous use of rozuvastatin at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia. The simultaneous use of rosuvastatin and gemfibrozil results in a 2-fold increase in 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 action 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 leads to a decrease in AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%, probably as a result of increased motility of the intestine caused by taking erythromycin. The simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of 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 the use of rosuvastatin. Based on studies of the interaction of rosuvastatin with digoxin, no clinically significant interaction has been identified. The results of in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of isoenzymes of the cytochrome P450 system. 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 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, as with rosuvastatin and other HMG-CoA reductase inhibitors, is higher at a dose of 40 mg. Determination of CPK activity should not be carried out after intense physical exertion or in the presence of other possible reasons for an increase in CPK activity due to the likely distortion of the results obtained. 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. It is not necessary to begin therapy if the repeated test confirms the initial activity of CPK (5 times higher than VGN). Patients should be warned of the need to immediately inform the doctor if new, previously unnoticed symptoms, unexplained muscle pain, weakness or cramps, especially associated with fever and malaise, appear. 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. It is recommended to carry out functional diagnostics of the liver before and within 3 months after the start of therapy. Impact on the ability to drive vehicles and control mechanisms Research has not been conducted to study the effect of the drug Tevastor on the ability to drive vehicles and work with equipment. At use of drug Tevastor it is necessary to be careful in connection with the fact that development of dizziness is possible.