Tevastor tablets ppo 10 mg No. 90
Compound
Tablets 5 mg. 1 tablet contains: active substance rosuvastatin (rosuvastatin calcium) 5.00 (5.21) mg; excipients: microcrystalline cellulose 47.82 mg, crospovidone 30.00 mg, lactose 54.97 mg, povidone-KZO 8.50 mg, sodium stearyl fumarate 3.50 mg; shell Opadry II 85P23426 orange (polyvinyl alcohol - partially hydrolyzed 1.800 mg, titanium dioxide (E171) 1.025 mg, macrogol-3350 0.909 mg, talc 0.666 mg, iron dye yellow oxide (E172) 0.075 mg, iron dye black oxide (E172) 0, 003 mg, sunset yellow dye (E110) 0.022 mg). Tablets 10 mg, 20 mg, 40 mg. 1 tablet contains: active substance rosuvastatin (rosuvastatin calcium) 10.00 (10.42)/20.00 (20.83)/40.00 (41.67) mg; excipients: microcrystalline cellulose 45.22/90.45/80.03 mg, crospovidone 30.00/60.00/60.00 mg, lactose 52.36/104.72/94.30 mg, povidone-KZO 8 .50/17.00/17.00 mg, sodium stearyl fumarate 3.50/7.00/7.00 mg; shell Opadry II 85P24155 pink (polyvinyl alcohol - partially hydrolyzed 1.800/3.600/3.600 mg, titanium dioxide (E171) 1.105/2.210/2.210 mg, macrogol-3350 0.909/1.818/1.818 mg, talc 0.666/1.332 /1.332 mg, iron dye Yellow oxide (E172) 0.009/0.018/0.018 mg, iron dye red oxide (E172) 0.005/0.010/0.010 mg, aluminum varnish (E 122) 0.005/0.009/0.009 mg, indigurine aluminum varnish (E132) 0.00 /0.003 mg).
Pharmacokinetics
Suction.
The maximum concentration (Cmax) of rosuvastatin in blood plasma is reached approximately 5 hours after oral administration. Absolute bioavailability is approximately 20%. Distribution. Rosuvastatin accumulates predominantly in the liver, the main organ for the synthesis of cholesterol and clearance of LDL cholesterol. Distribution volume (Vd) - approximately 134 l. Plasma protein binding (mainly albumin) is approximately 90%.
Metabolism. It is biotransformed to a small extent (about 10%), being a non-core substrate for metabolism by enzymes of the cytochrome P450 system. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. The isoenzymes CYP2C19, CYP3A4 and CYP2D6 are involved in metabolism to a lesser extent. The main identified metabolites of rosuvastatin are N-dismethyl and lactone metabolites. The N-dismethyl metabolite is approximately 50% less active than rosuvastatin; lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity of inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites.
Excretion. About 90% of the rosuvastatin dose is excreted unchanged in the feces. The remainder is excreted in the urine. The half-life (T1/2) is approximately 19 hours. T1/2 does not change with increasing doses of the drug. The average plasma clearance is approximately 50 l/h (coefficient of variation - 21.7%). As in the case of other HMG-CoA reductase inhibitors, the membrane anion transporter Xc is involved in the process of “hepatic” uptake of rosuvastatin, which plays an important role in the hepatic elimination of rosuvastatin.
Pharmacokinetics in special clinical cases.
Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.
Comparative studies of the pharmacokinetics of rosuvastatin in Japanese and Chinese patients living in Asia showed an approximately two-fold increase in the mean values of the area under the curve of hepatic transaminases or any increase in the activity of hepatic transaminases (more than 3 times compared with the upper limit of normal (ULN) ), severe renal dysfunction (creatinine clearance less than 30 ml/min); myopathy; simultaneous use of cyclosporine; pregnancy; breastfeeding period; lack of reliable methods of contraception; lactose intolerance; lactase deficiency or glucose-galactose malabsorption (the drug contains lactose); age under 18 years (insufficient data on effectiveness and safety); severe liver dysfunction (more than 9 points on the Child-Pugh scale) (no experience with use).
For tablets 40 mg. Hypersensitivity to rosuvastatin or any of the components of the drug; simultaneous use of cyclosporine, pregnancy; breastfeeding period; lack of reliable methods of contraception; lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose); age under 18 years (insufficient data on efficacy and safety), liver disease in the active phase, including a persistent increase in the activity of “liver” transaminases and any increase in the activity of “liver” transaminases (more than 3 times compared to ULN).
Patients with risk factors for myopathy/rhabdomyolysis: renal failure (creatinine clearance less than 60 ml/min); hypothyroidism; personal or family analysis of muscle diseases; myotoxicity due to a history of taking other HMG-Co-A reductase inhibitors or fibrates; excessive alcohol consumption; conditions that can lead to increased plasma concentrations of rosuvastatin; simultaneous use of fibrates; use in Asian patients; severe liver dysfunction (more than 9 points on the Child-Pugh scale) (no experience with use).
Directions for use and doses
The drug is taken orally at any time of the day, regardless of food intake. The tablet should be swallowed whole with water, without chewing or crushing. If it is necessary to take the drug at a dose of 5 mg, the 10 mg tablet should be divided in half. Before starting therapy with Tevastor®, the patient should begin following a standard lipid-lowering diet and continue to follow it during treatment. The dose of the drug should be individualized depending on the indication and therapeutic response, taking into account current recommendations for target lipid levels. The recommended starting dose of Tevastor® for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, is 5 or 10 mg 1 time / day. When choosing an initial dose, one should be guided by the patient's cholesterol level and take into account the risk of developing cardiovascular complications, and the potential risk of side effects should be assessed. If necessary, after 4 weeks the dose can be increased. Patients with severe hypercholesterolemia and at high risk of cardiovascular complications (especially patients with familial hypercholesterolemia) who did not achieve the desired result when taking a dose of 20 mg during 4 weeks of therapy should be under under medical supervision due to a possible increased risk of side effects. Particularly 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 parameters is necessary. In elderly patients (over 65 years of age), it is recommended to start treatment with a dose of 5 mg. No dosage adjustment is required in patients with mild or moderate renal impairment. The use of Tevastor® in any doses is contraindicated in severe renal failure (creatinine clearance less than 30 ml/min). The use of Tevastor® at a dose of 40 mg is contraindicated in patients with moderate renal impairment (creatinine clearance less than 60 ml/min). For patients with moderate renal impairment, an initial dose of 5 mg is recommended. For Asian patients, the recommended starting dose is 5 mg. The use of Tevastor® at a dose of 40 mg is contraindicated in patients of the Asian race. Prescribing Tevastor® at a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy. When prescribing the drug in doses of 10 mg and 20 mg, the recommended initial dose for patients in this group is 5 mg. Carriers of the SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA genotypes showed an increase in exposure (AUC) to rosuvastatin compared to carriers of the SLCO1B1 c.521TT and ABCG2c.421CC genotypes. For patients carrying genotypes c.521CC or c.421AA, the recommended maximum daily dose of Tevastor® is 20 mg 1 time / day (see sections “Pharmacokinetics”, “Special instructions” and “Drug interactions”). When using Tevastor® with cyclosporine and HIV protease inhibitors (including a combination of ritonavir with atazanavir, lopinavir), the risk of myopathy (including rhabdomyolysis) increases, so alternative therapy or temporary withdrawal of Tevastor® should be considered. If the simultaneous use of these drugs is unavoidable, the benefit/risk ratio of concomitant therapy with Tevastor® should be assessed and the possibility of reducing its dose should be considered.
Storage conditions
Store at a temperature not exceeding 25 °C. Keep out of the reach of children.
Best before date
2 years.
Do not use after the expiration date stated on the package.
special instructions
Proteinuria, mostly of renal origin, detected by testing, is observed in patients taking rosuvastatin at a dose of 40 mg and above, 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 with the use of rosuvastatin at a dose of 40 mg. When using Tevastor® at a dose of 40 mg, it is recommended to monitor renal function indicators. Effects on skeletal muscles (myalgia, myopathy and very rarely rhabdomyolysis) are observed in patients taking Tevastor®, in particular at a dose of more than 20 mg. Very rare cases of rhabdomyolysis have been reported when ezetimibe was used 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 carried out after intense physical activity or in the presence of other possible reasons for increased CPK activity due to the possible distortion of the results obtained. If the initial CPK activity is significantly increased (5 times higher than ULN), a repeat measurement should be taken after 5-7 days. Therapy should not be started if a repeat test confirms initial CPK activity (5 times the ULN). Patients should be warned to immediately notify their physician if they experience new, previously unrecognized symptoms, unexplained muscle pain, weakness, or cramps, especially when accompanied by fever and malaise. Therapy should be discontinued if CPK activity is 5 times the ULN or if severe muscle symptoms causing persistent discomfort are present. When symptoms disappear and CPK activity normalizes, re-use of rosuvastatin should be considered at 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.
Description
Tablets 5 mg.
Round, biconvex, film-coated tablets ranging from light yellow or light orange (a grayish tint is possible) to orange, engraved with “N” on one side and “5” on the other. On a cross section, the core is white to almost white. Tablets 10 mg. Round, biconvex, light pink to pink film-coated tablets debossed with “N” on one side and “10” on the other. On a cross section, the core is white to almost white.
Tablets 20 mg. Round biconvex film-coated tablets
light pink to pink, with "N" engraved on one side and "20" on the side
another. On a cross section, the core is white to almost white.
Tablets 40 mg. Oval, light pink film-coated tablets
to pink, with "N" engraved on one side and "40" on the other. On a cross section, the core is white to almost white.
Conditions for dispensing from pharmacies
On prescription
Dosage form
film-coated tablets.
Use in children
Contraindicated in children and adolescents under 18 years of age.
Manufacturer and organization accepting consumer complaints
Teva Pharmaceutical Enterprises Ltd.
Pharmacodynamics
Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglugaryl coenzyme A into mevalonate, a precursor of cholesterol (Cc). The main target of action of rosuvastatin is the liver, where the synthesis of cholesterol and the catabolism of low-density lipoproteins (LDL) take place. 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 very low-density lipoprotein (VLDL) synthesis, thereby reducing the total amount of LDL and VLDL. Rosuvastatin reduces the increased concentration of low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides (TG), increases the concentration of high-density lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (ApoB), HDL-C, VLDL-C, VLDL-TG and increases the concentration of apolipoprotein A-1 (ApoA-1), reduces the LDL-C/HDL-C ratio, total C/HDL-C and non-HDL-C/HDL-C and the ApoB/ApoA- ratio. 1. The therapeutic effect appears within 1 week after the start of rosuvastatin 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 use.
Side effects
Side effects observed when taking Tevastor® are usually mild and go away on their own.
As with other HMG-CoA reductase inhibitors, the incidence of side effects is mainly dose-dependent. Determination of the frequency of adverse reactions: often (> 1/100, < 1/10); uncommon (> 1/1000, < 1/100); rare (> 1/10,000, < 1/1000); very rare (< 1/10,000), unknown frequency (cannot be calculated from available data). From the immune system: rarely - hypersensitivity reactions, including angioedema. From the endocrine system: often - type 2 diabetes mellitus.
From the central nervous system (CNS): often - headache, dizziness.
From the digestive system: often - constipation, nausea, abdominal pain; rarely - pancreatitis.
From the skin: infrequently - itching, rash, urticaria.
From the musculoskeletal system: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis.
Other: often - asthenic syndrome.
Description of unwanted effects
From the urinary system: patients receiving Tevastor® may experience proteinuria. Changes in the amount of protein in the urine (from none or trace amounts to ++ or more) are observed in less than 1% of patients receiving the drug at a dose of 10-20 mg and in approximately 3% of patients receiving the drug at a dose of 40 mg. A slight change in the amount of protein in the urine was noted when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not indicate the onset of acute or progression of existing kidney disease.
From the musculoskeletal system: 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 creatine phosphokinase (CPK) activity is observed in a small number of patients taking rosuvastatin. In most cases it was minor, asymptomatic and temporary. If CK activity increases (more than 5 times the upper limit of normal), therapy should be suspended.
From the liver: a dose-dependent increase in the activity of “liver” transaminases in a small number of patients. In most cases it is minor, asymptomatic and temporary.
Laboratory indicators: increased concentrations of glucose, bilirubin, gammaglutamyltransferase activity, alkaline phosphatase, thyroid dysfunction.
Post-marketing use
From the blood and lymphatic system: unknown frequency - thrombocytopenia.
From the digestive system: very rarely - jaundice, hepatitis; rarely - increased activity of liver transaminases; unknown frequency - diarrhea.
From the musculoskeletal system: very rarely - arthralgia; unknown frequency - immune-mediated necrotizing myopathy.
From the side of the central nervous system: very rarely - polyneuropathy, memory loss.
From the respiratory system: unknown frequency - cough, shortness of breath.
From the urinary system: very rarely - hematuria.
From the skin and subcutaneous fat: unknown frequency - Stevens-Johnson syndrome.
From the reproductive system: unknown frequency - gynecomastia.
Other: unknown frequency - peripheral edema.
The following side effects have been reported with some statins: depression, sleep disturbances including insomnia and nightmares, and sexual dysfunction. Isolated cases of interstitial lung disease have been reported, especially with long-term use of the drugs.
Use during pregnancy and breastfeeding
Tevastor® is contraindicated during pregnancy and breastfeeding. If pregnancy is diagnosed 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 inhibiting HMG-CoA reductase outweighs the benefits of using the drug. There is no data on the release of rosuvastatin into breast milk, therefore, if it is necessary to use the drug Tevastor® during lactation, breastfeeding should be discontinued.
Interaction
With the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers, while the plasma concentration of cyclosporine did not change. Initiating rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (eg, warfarin) may lead to an increase in the International Normalized Ratio (INR). Discontinuation of rosuvastatin or reduction of its dose may lead to a decrease in MHO (in such cases, monitoring of MHO is recommended). The simultaneous use of rosuvastatin 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. An increased risk of side effects due to the pharmacodynamic interaction between rosuvastatin and ezetimibe cannot be excluded. The simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax in blood plasma and AUC of rosuvastatin. According to special studies, no relevant pharmacokinetic interaction with fenofibrate has been noted, but pharmacodynamic interaction is possible. Hemofibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increase the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors (probably due to the fact that HMG-CoA inhibitors can cause myopathy when used as monotherapy) . Although the exact mechanism of interaction of rosuvastatin with protease inhibitors is unknown, their simultaneous use may cause a persistent increase in the effect of rosuvastatin. In pharmacokinetic studies in healthy volunteers, coadministration of 20 mg rosuvastatin and a combination of protease inhibitors (lopinavir 400 mg/ritonavir 100 mg) caused approximately 2- and 5-fold increases 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 antacid suspensions containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied. Concomitant use of rosuvastatin and erythromycin leads to a decrease in rosuvastatin AUC by 20% and rosuvastatin Cmax by 30%, probably as a result of increased intestinal motility caused by erythromycin. Concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. This increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives while using 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 showed 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 involving the cytochrome P450 system are not expected.
Overdose
When taking several daily doses simultaneously, the pharmacokinetic parameters of rosuvastatin do not change. Treatment: in case of overdose, symptomatic therapy is carried out if necessary; monitoring of liver function and CPK activity is necessary. There is no specific antidote. Hemodialysis is not effective.
Impact on the ability to drive vehicles and operate machinery
Studies aimed at studying the effect of Tevastor® on the ability to drive vehicles and operate machinery have not been conducted. When using the drug Tevastor®, caution should be exercised due to the fact that dizziness may develop.
Tevastor
With the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers, while the plasma concentration of cyclosporine did not change. Simultaneous use leads to an 11-fold increase in the plasma concentration of rosuvastatin in the blood plasma.
Initiating rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (eg, warfarin) may lead to an increase in prothrombin time (increase in MHO). Discontinuation of rosuvastatin or reduction of its dose may lead to a decrease in MHO (in such cases, monitoring of MHO is recommended).
Concomitant use of rosuvastatin and ezetimibe did not reveal changes in AUC or Cmax for either drug. However, their pharmacodynamic interaction and the occurrence of adverse effects cannot be excluded.
The simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax in blood plasma and AUC of rosuvastatin. According to special studies, no relevant pharmacokinetic interaction with fenofibrate has been noted, but pharmacodynamic interaction is possible. Hemofibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increase the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors (probably due to the fact that HMG-CoA inhibitors can cause myopathy when used as monotherapy) .
Although the exact mechanism of interaction of rosuvastatin with protease inhibitors is unknown, their simultaneous use may cause a persistent increase in the effect of rosuvastatin. In pharmacokinetic studies in healthy volunteers, coadministration of 20 mg rosuvastatin and a combination of protease inhibitors (lopinavir 400 mg/ritonavir 100 mg) caused approximately 2- and 5-fold increases 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 antacid suspensions containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.
Concomitant use of rosuvastatin and erythromycin leads to a decrease in rosuvastatin AUC by 20% and rosuvastatin Cmax by 30%, probably as a result of increased intestinal motility caused by erythromycin.
Concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. This increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives while using 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 showed 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). Co-administration of rosuvastatin and itraconazole (CYP3A4 inhibitor) increases the AUC of rosuvastatin by 28% (clinically insignificant). Thus, interactions involving the cytochrome P450 system are not expected.
Tevastor, 5 mg, film-coated tablets, 30 pcs.
Inside,
at any time of the day, regardless of food intake. The tablet should be swallowed whole with water, without chewing or crushing.
If it is necessary to take the drug at a dose of 5 mg, the 10 mg tablet should be divided in half.
Before starting therapy with Tevastor®, the patient should begin following a standard lipid-lowering diet and continue to follow it during treatment. The dose of the drug should be individualized depending on the indication and therapeutic response, taking into account current recommendations for target lipid levels. The recommended starting dose of Tevastor® for patients starting to take the drug or for patients switched from taking 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 level and take into account the risk of developing cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, after 4 weeks the dose can be increased.
Patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially patients with familial hypercholesterolemia)
Those who did not achieve the desired result when taking a dose of 20 mg during 4-week therapy should be under the supervision of a physician when increasing the dose of the drug to 40 mg due to a possible increase in the risk of side effects.
Particularly 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 parameters is necessary.
In elderly patients (over 65 years old)
It is recommended to start treatment with a dose of 5 mg.
Patients with kidney failure
In patients with renal failure, no dose adjustment is required. The use of Tevastor® in any dose is contraindicated in severe renal failure (creatinine clearance less than 30 ml/min). The use of Tevastor® at a dosage of 40 mg is contraindicated in patients with moderate renal impairment (creatinine clearance less than 60 ml/min). For patients with moderate renal impairment, an initial dose of 5 mg is recommended.
Special populations. Ethnic groups.
When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin was noted among the Japanese and Chinese (see “Special Instructions”). This fact should be taken into account when using the drug Tevastor® in these groups of patients. For Asian patients, the recommended starting dose is 5 mg. The use of Tevastor® at a dose of 40 mg is contraindicated in patients of the Asian race.
Genetic polymorphism.
Carriers of the SLCO1B1 (OATP1B1) c.52ICC and ABCG2 (BCRP) c.421AA genotypes showed an increase in exposure (AUC) to rosuvastatin compared to carriers of the SLCO1B1 c.521TT and ABCG2 c.421CC genotypes. For patients carrying genotypes c.521CC or c.421AA, the recommended maximum daily dose of Tevastor® is 20 mg once a day (see “Pharmacokinetics”, “Special instructions” and “Interaction”).
Predisposition to myopathy.
The use of Tevastor® at a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy (see “Special Instructions”). When using doses of 10 and 20 mg, an initial dose of 5 mg is recommended for patients in this group.
Concomitant therapy.
Rosuvastatin binds to various transport proteins (in particular OATP1B1 and BCRP). When using Tevastor® with cyclosporine and HIV protease inhibitors (including a combination of ritonavir with atazanavir, lopinavir), the risk of myopathy (including rhabdomyolysis) increases, so alternative therapy or temporary withdrawal of Tevastor® should be considered. If the simultaneous use of these drugs is unavoidable, the benefit-risk ratio of concomitant therapy with Tevastor® should be assessed and the possibility of reducing its dose should be considered.
