Product Overview
Composition
active substance:
Excipients:
microcrystalline cellulose - 36.0 mg,
calcium hydrogen phosphate dihydrate - 13.0 mg,
crospovidone - 9.0 mg,
magnesium stearate - 1.8 mg;
film casing:
[hypromellose - 3.2400 mg, talc - 1.0800 mg, titanium dioxide - 0.5724 mg, macrogol 4000 (polyethylene glycol 4000) - 0.4860 mg, iron oxide red (iron oxide) - 0.0216 mg] or [ dry mix for film coating containing hypromellose (60%), talc (20%), titanium dioxide (10.6%), macrogol 4000 (polyethylene glycol 4000) (9%), iron oxide red (iron oxide) (0.4 %)] - 5.4000 mg
pharmachologic effect
Rosuvastatin is a selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonic acid, a precursor of cholesterol. The main target of the action of rosuvastatin is the liver, where the synthesis of cholesterol (Xc) and catabolism of low density lipoprotein cholesterol (LDL-C) are carried out.
The therapeutic effect develops within one 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 the 4th week of therapy and is maintained with regular administration of the drug.
Rosuvastatin is effective in adult patients with hypercholesterolemia, with or without hypertriglyceridemia, including those with diabetes mellitus and familial hypercholesterolemia.
An additive effect is observed in combination with fenofibrate (in relation to the concentration of TG) and with niacin in lipid-lowering doses (in relation to the concentration of HDL-C), however, the possibility of such combinations should be assessed by the attending physician taking into account the possible risks
Rosuvastatin increases the number of LDL-C receptors on the surface of liver cells, increasing the uptake and catabolism of LDL-C, which in turn leads to inhibition of the synthesis of very low density lipoprotein cholesterol (VLDL-cholesterol), thereby decreasing the total amount of LDL-C and Xc- VLDL.
Rosuvastatin reduces elevated concentrations of 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), high-density non-lipoprotein cholesterol (HDL-C, non-HDL) VLDL, TG and increases the concentration of apolipoprotein A I (ApoA-I), reduces the ratio of LDL-C / HDL-cholesterol, total cholesterol / HDL-cholesterol and C-non-LDL / HDL-cholesterol and the apoV / apoA-I ratio.
The therapeutic effect develops within one 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 the 4th week of therapy and is maintained with regular administration of the drug.
Rosuvastatin is effective in adult patients with hypercholesterolemia, with or without hypertriglyceridemia, including those with diabetes mellitus and familial hypercholesterolemia.
An additive effect is observed in combination with fenofibrate (in relation to the concentration of TG) and with niacin in lipid-lowering doses (in relation to the concentration of HDL-C), however, the possibility of such combinations should be assessed by the attending physician taking into account the possible risks
Indications
- Primary hypercholesterolemia according to the Fredrickson classification (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet, when diet and other non-drug treatments (e.g. exercise, weight loss) are insufficient;
- familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-containing therapy (for example, LDL apheresis), or in cases where such therapy is not effective enough;
- hypertriglyceridemia (type IV according to the Fredrickson classification) as an addition to the diet;
- to slow the progression of atherosclerosis as an adjunct to the diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL-C;
Application during pregnancy and lactation
Rosuvastatin is contraindicated in pregnancy and lactation. Women of reproductive age must use adequate contraceptive methods.
Since Xc and substances synthesized from Xc are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase for the fetus outweighs the benefits of using rosuvastatin during pregnancy. In the event of pregnancy during therapy, the use of the drug should be discontinued immediately.
There are no data on the excretion of rosuvastatin in breast milk (it is known that other HMG-CoA reductase inhibitors can be excreted in breast milk), therefore, during breastfeeding, the use of the drug should be discontinued. The FDA category of action on the fetus is X.
Since Xc and substances synthesized from Xc are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase for the fetus outweighs the benefits of using rosuvastatin during pregnancy. In the event of pregnancy during therapy, the use of the drug should be discontinued immediately.
There are no data on the excretion of rosuvastatin in breast milk (it is known that other HMG-CoA reductase inhibitors can be excreted in breast milk), therefore, during breastfeeding, the use of the drug should be discontinued. The FDA category of action on the fetus is X.
Recommendations for use
Inside, do not chew or crush the tablet, swallow it whole with water. The drug can be prescribed at any time of the day, regardless of the time of the meal.
Before starting therapy with Rosuvastatin, the patient should begin to follow a standard cholesterol-lowering diet and continue to follow it during treatment.
The dose of the drug should be selected individually depending on the goals of therapy and the therapeutic response to treatment, taking into account the current recommendations for target lipid concentrations. The recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 or 10 mg of Rosuvastatin 1 time / day. When choosing an initial dose, one should be guided by the individual cholesterol content and take into account the possible risk of cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, the dose can be increased to a larger one after 4 weeks.
In connection with the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug (see the "Side Effects" section), an increase in the dose to 40 mg, after taking an additional dose above the recommended initial dose for 4 weeks therapy, can be carried out only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia), who did not achieve the desired result of therapy when taking a dose of 20 mg, and who will be under the supervision of a specialist.
Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor. After 2-4 weeks of therapy and / or with an increase in the dose of the drug Rosuvastatin, it is necessary to monitor the parameters of lipid metabolism (if necessary, a dose adjustment is required). The use of the drug in a higher dose than 40 mg is not justified due to increased side effects and in most cases is not recommended. Elderly patients No dose adjustment required.
Patients with renal impairment:
No dose adjustment is required in patients with mild to moderate renal impairment. In patients with severe renal impairment (CC less than 30 ml / min), the use of Rosuvastatin is contraindicated. The use of the drug in a dose of 40 mg is contraindicated in patients with moderate impairment of renal function (CC 30-60 ml / min). An initial dose of 5 mg is recommended for patients with moderate impairment of renal function.
Patients with hepatic impairment: Rosuvastatin is contraindicated in patients with active liver disease. 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 among the Japanese and Chinese was noted (see the section "Special instructions"). This fact should be taken into account when prescribing Rosuvastatin to these groups of patients.
When prescribing doses of 10 and 20 mg, the recommended starting dose for patients of the Mongoloid race is 5 mg. The appointment of the drug in a dose of 40 mg is contraindicated in patients of the Mongoloid race (see section "Contraindications"). Genetic polymorphism Carriers of SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA genotypes showed an increase in exposure (AUC) to rosuvastatin compared to carriers of SLCO1B1 c.521TT and ABCG2 c.421CC genotypes. For patients with c.521CC or c.421AA genotypes, the recommended maximum dose of Rosuvastatin is 20 mg 1 time / day.
Patients predisposed to myopathy Prescription of the drug at a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy. When prescribing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg. Concomitant therapy Rosuvastatin binds to various transport proteins (in particular, OATP1B1 and BCRP).
When Rosuvastatin is used together with drugs (such as cyclosporine, some HIV protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and / or tipranavir) that increase the plasma concentration of rosuvastatin due to interaction with transport proteins, the risk of myopathy (including rhabdomyolysis )
In such cases, the possibility of prescribing alternative therapy or temporary discontinuation of the drug Rosuvastatin should be evaluated. If the use of the above drugs is necessary, the balance of benefits and risks of concomitant therapy with Rosuvastatin should be evaluated and the possibility of reducing its dose should be considered
Before starting therapy with Rosuvastatin, the patient should begin to follow a standard cholesterol-lowering diet and continue to follow it during treatment.
The dose of the drug should be selected individually depending on the goals of therapy and the therapeutic response to treatment, taking into account the current recommendations for target lipid concentrations. The recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 or 10 mg of Rosuvastatin 1 time / day. When choosing an initial dose, one should be guided by the individual cholesterol content and take into account the possible risk of cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, the dose can be increased to a larger one after 4 weeks.
In connection with the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug (see the "Side Effects" section), an increase in the dose to 40 mg, after taking an additional dose above the recommended initial dose for 4 weeks therapy, can be carried out only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia), who did not achieve the desired result of therapy when taking a dose of 20 mg, and who will be under the supervision of a specialist.
Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor. After 2-4 weeks of therapy and / or with an increase in the dose of the drug Rosuvastatin, it is necessary to monitor the parameters of lipid metabolism (if necessary, a dose adjustment is required). The use of the drug in a higher dose than 40 mg is not justified due to increased side effects and in most cases is not recommended. Elderly patients No dose adjustment required.
Patients with renal impairment:
No dose adjustment is required in patients with mild to moderate renal impairment. In patients with severe renal impairment (CC less than 30 ml / min), the use of Rosuvastatin is contraindicated. The use of the drug in a dose of 40 mg is contraindicated in patients with moderate impairment of renal function (CC 30-60 ml / min). An initial dose of 5 mg is recommended for patients with moderate impairment of renal function.
Patients with hepatic impairment: Rosuvastatin is contraindicated in patients with active liver disease. 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 among the Japanese and Chinese was noted (see the section "Special instructions"). This fact should be taken into account when prescribing Rosuvastatin to these groups of patients.
When prescribing doses of 10 and 20 mg, the recommended starting dose for patients of the Mongoloid race is 5 mg. The appointment of the drug in a dose of 40 mg is contraindicated in patients of the Mongoloid race (see section "Contraindications"). Genetic polymorphism Carriers of SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA genotypes showed an increase in exposure (AUC) to rosuvastatin compared to carriers of SLCO1B1 c.521TT and ABCG2 c.421CC genotypes. For patients with c.521CC or c.421AA genotypes, the recommended maximum dose of Rosuvastatin is 20 mg 1 time / day.
Patients predisposed to myopathy Prescription of the drug at a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy. When prescribing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg. Concomitant therapy Rosuvastatin binds to various transport proteins (in particular, OATP1B1 and BCRP).
When Rosuvastatin is used together with drugs (such as cyclosporine, some HIV protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and / or tipranavir) that increase the plasma concentration of rosuvastatin due to interaction with transport proteins, the risk of myopathy (including rhabdomyolysis )
In such cases, the possibility of prescribing alternative therapy or temporary discontinuation of the drug Rosuvastatin should be evaluated. If the use of the above drugs is necessary, the balance of benefits and risks of concomitant therapy with Rosuvastatin should be evaluated and the possibility of reducing its dose should be considered
Contraindications
Daily dose up to 30 mg:
hypersensitivity to rosuvastatin; liver disease in the active phase (including a persistent increase in the activity of hepatic transaminases and an increase in the activity of hepatic transaminases in the blood serum by more than 3 times compared with VGN); severe renal failure (Cl creatinine.
Daily dose of 30 mg or more: hypersensitivity to rosuvastatin; liver disease in the active phase (including a persistent increase in the activity of hepatic transaminases and an increase in the activity of hepatic transaminases in the blood serum by more than 3 times compared with VGN); moderate to severe renal failure (Cl creatinine)
hypersensitivity to rosuvastatin; liver disease in the active phase (including a persistent increase in the activity of hepatic transaminases and an increase in the activity of hepatic transaminases in the blood serum by more than 3 times compared with VGN); severe renal failure (Cl creatinine.
Daily dose of 30 mg or more: hypersensitivity to rosuvastatin; liver disease in the active phase (including a persistent increase in the activity of hepatic transaminases and an increase in the activity of hepatic transaminases in the blood serum by more than 3 times compared with VGN); moderate to severe renal failure (Cl creatinine)
Side effects
Side effects observed with rosuvastatin 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. WHO classification of the incidence of side effects: very often (≥1 / 10); often (≥1 / 100,
on the part of the blood and lymphatic system: the frequency is unknown - thrombocytopenia.
On the part of the immune system: rarely - hypersensitivity reactions, including angioedema.
From the endocrine system: often - type 2 diabetes mellitus.
From the nervous system: often - headache, dizziness; very rarely - loss or decrease in memory; frequency unknown - peripheral neuropathy.
From the respiratory system, chest and mediastinal organs: the frequency is unknown - cough, shortness of breath.
From the digestive system: often - constipation, nausea, abdominal pain; rarely - pancreatitis; very rarely - jaundice, hepatitis; frequency unknown - diarrhea. When using rosuvastatin, a dose-dependent increase in the activity of hepatic transaminases in the blood plasma is observed in a small number of patients. In most cases, it is minor, asymptomatic, and temporary.
On the part of the skin and subcutaneous tissues: infrequently - itching, skin rash, urticaria; frequency unknown - Stevens-Johnson syndrome.
From the musculoskeletal system and connective tissue: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis (with or without acute renal failure); very rarely - arthralgia; frequency unknown - immune-mediated necrotizing myopathy. A dose-dependent increase in plasma CPK activity is observed in a small number of patients taking rosuvastatin. In most cases, it is minor, asymptomatic, and temporary. In the case of an increase in the activity of CPK in the blood plasma more than 5 times higher than the ULN, therapy should be suspended.
From the side of the kidneys and urinary tract: in patients receiving therapy with rosuvastatin, proteinuria may be detected. Changes in the amount of protein in urine (from no or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10–20 mg of rosuvastatin and in about 3% of patients receiving a dose of 40 mg / day. A slight change in the amount of protein in the urine was noted with a dose of 20 mg. In most cases, proteinuria diminishes or disappears with therapy and does not mean acute or progression of existing kidney disease; very rarely - hematuria.
From the genitals and mammary gland: the frequency is unknown - gynecomastia.
General disorders and disorders at the injection site: often - asthenic syndrome; frequency unknown - peripheral edema. Laboratory indicators: hyperglycemia, an increase in the concentration of bilirubin in the blood plasma, the activity of GGTP, ALP in the blood plasma, a change in the serum concentration of thyroid hormones.
With the use of some HMG-CoA reductase inhibitors (statins), the following side effects have been reported: depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction, an increase in the concentration of glycosylated hemoglobin. Isolated cases of interstitial lung disease have been reported, especially with long-term use of these agents
As with other HMG-CoA reductase inhibitors, the incidence of side effects is mainly dose-dependent. WHO classification of the incidence of side effects: very often (≥1 / 10); often (≥1 / 100,
on the part of the blood and lymphatic system: the frequency is unknown - thrombocytopenia.
On the part of the immune system: rarely - hypersensitivity reactions, including angioedema.
From the endocrine system: often - type 2 diabetes mellitus.
From the nervous system: often - headache, dizziness; very rarely - loss or decrease in memory; frequency unknown - peripheral neuropathy.
From the respiratory system, chest and mediastinal organs: the frequency is unknown - cough, shortness of breath.
From the digestive system: often - constipation, nausea, abdominal pain; rarely - pancreatitis; very rarely - jaundice, hepatitis; frequency unknown - diarrhea. When using rosuvastatin, a dose-dependent increase in the activity of hepatic transaminases in the blood plasma is observed in a small number of patients. In most cases, it is minor, asymptomatic, and temporary.
On the part of the skin and subcutaneous tissues: infrequently - itching, skin rash, urticaria; frequency unknown - Stevens-Johnson syndrome.
From the musculoskeletal system and connective tissue: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis (with or without acute renal failure); very rarely - arthralgia; frequency unknown - immune-mediated necrotizing myopathy. A dose-dependent increase in plasma CPK activity is observed in a small number of patients taking rosuvastatin. In most cases, it is minor, asymptomatic, and temporary. In the case of an increase in the activity of CPK in the blood plasma more than 5 times higher than the ULN, therapy should be suspended.
From the side of the kidneys and urinary tract: in patients receiving therapy with rosuvastatin, proteinuria may be detected. Changes in the amount of protein in urine (from no or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10–20 mg of rosuvastatin and in about 3% of patients receiving a dose of 40 mg / day. A slight change in the amount of protein in the urine was noted with a dose of 20 mg. In most cases, proteinuria diminishes or disappears with therapy and does not mean acute or progression of existing kidney disease; very rarely - hematuria.
From the genitals and mammary gland: the frequency is unknown - gynecomastia.
General disorders and disorders at the injection site: often - asthenic syndrome; frequency unknown - peripheral edema. Laboratory indicators: hyperglycemia, an increase in the concentration of bilirubin in the blood plasma, the activity of GGTP, ALP in the blood plasma, a change in the serum concentration of thyroid hormones.
With the use of some HMG-CoA reductase inhibitors (statins), the following side effects have been reported: depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction, an increase in the concentration of glycosylated hemoglobin. Isolated cases of interstitial lung disease have been reported, especially with long-term use of these agents
Interaction
Inhibitors of transport proteins: rosuvastatin binds to some transport proteins, in particular, OATP1B1 and BCRP. The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of myopathy. Cyclosporine: with the simultaneous use of rosuvastatin and cyclosporin, the AUC of rosuvastatin was, on average, 7 times higher than that observed in healthy volunteers.
Rosuvastatin does not affect the plasma concentration of cyclosporine. Rosuvastatin is contraindicated in patients taking cyclosporine. Human immunodeficiency virus (HIV) protease inhibitors: although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors and rosuvastatin can lead to a significant increase in the AUC of rosuvastatin.
While taking the drug Rosuvastatin with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), patients are recommended an initial dose of 5 mg; taking at a dose of 40 mg is contraindicated when administered together with fibrates. Ezetimibe: 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 (see table).
An increase in the risk of side effects due to the pharmacodynamic interaction between Rosuvastatin and ezetimibe cannot be ruled out. Antacids: the simultaneous use of rosuvastatin and antacid suspensions containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by about 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.
Erythromycin: the simultaneous use of rosuvastatin and erythromycin leads to a decrease in the AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction can occur as a result of increased intestinal motility caused by the intake of erythromycin. Isozymes of the cytochrome P450 system: 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. Therefore, the interaction of rosuvastatin with other drugs at the metabolic level with the participation of isoenzymes of the cytochrome P450 system is not expected.
There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes). Fusidic acid: studies on the interaction of rosuvastatin and fusidic acid have not been conducted.
As with other statins, there have been post-marketing reports of cases of rhabdomyolysis when rosuvastatin and fusidic acid are taken together. Patients must be closely monitored. If necessary, it is possible to temporarily stop taking the drug Rosuvastatin.
Rosuvastatin does not affect the plasma concentration of cyclosporine. Rosuvastatin is contraindicated in patients taking cyclosporine. Human immunodeficiency virus (HIV) protease inhibitors: although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors and rosuvastatin can lead to a significant increase in the AUC of rosuvastatin.
A pharmacokinetic study but the simultaneous use of 20 mg rosuvastatin with a combined preparation containing two HIV protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers led to an increase in AUC (0-24) and Cmax of rosuvastatin by approximately 2 and 5 times, respectively. Therefore, concomitant use of rosuvastatin and HIV protease inhibitors is not recommended. Gemfibrozil and other lipid-lowering agents: the combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax in blood plasma and AUC of rosuvastatin (see the section "Special instructions").
Based on specific interaction data, no pharmacokinetically significant interaction with fenofibrate is expected, pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g / day) increased the risk of myopathy when used simultaneously with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when used as monotherapy (see the section "Special instructions").
While taking the drug Rosuvastatin with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), patients are recommended an initial dose of 5 mg; taking at a dose of 40 mg is contraindicated when administered together with fibrates. Ezetimibe: 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 (see table).
An increase in the risk of side effects due to the pharmacodynamic interaction between Rosuvastatin and ezetimibe cannot be ruled out. Antacids: the simultaneous use of rosuvastatin and antacid suspensions containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by about 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.
Erythromycin: the simultaneous use of rosuvastatin and erythromycin leads to a decrease in the AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction can occur as a result of increased intestinal motility caused by the intake of erythromycin. Isozymes of the cytochrome P450 system: 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. Therefore, the interaction of rosuvastatin with other drugs at the metabolic level with the participation of isoenzymes of the cytochrome P450 system is not expected.
There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes). Fusidic acid: studies on the interaction of rosuvastatin and fusidic acid have not been conducted.
As with other statins, there have been post-marketing reports of cases of rhabdomyolysis when rosuvastatin and fusidic acid are taken together. Patients must be closely monitored. If necessary, it is possible to temporarily stop taking the drug Rosuvastatin.
Overdose
Symptoms: the clinical picture of an overdose has not been described.
With a single intake of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.
Treatment: symptomatic, control of liver function and CPK activity is necessary; there is no specific antidote, hemodialysis is ineffective.
Special instructions
Impaired renal function. In patients who received high doses of rosuvastatin (in particular 40 mg / day), tubular proteinuria was observed, which was detected using test strips and in most cases was intermittent or short-term. This proteinuria is not indicative of acute disease or progression of concomitant kidney disease.
The incidence of serious renal dysfunction observed in post-marketing studies of rosuvastatin is higher with a dose of 40 mg / day. In patients taking the drug at a dose of 30 or 40 mg / day, it is recommended to monitor renal function indicators during treatment (at least once every 3 months). Influence on the musculoskeletal system.
When using rosuvastatin in all doses, but especially in doses exceeding 20 mg / day, the following effects on the musculoskeletal system have been reported: myalgia, myopathy, in rare cases, rhabdomyolysis. There have been very rare cases of rhabdomyolysis with the simultaneous use of HMG-CoA reductase inhibitors and ezetimibe. This combination should be used with caution as pharmacodynamic interaction cannot be excluded. As in the case of other HMG-CoA reductase inhibitors, the frequency of rhabdomyolysis with post-marketing use of rosuvastatin is higher with a dose of 40 mg / day
Determination of CPK activity. CPK activity cannot be determined after intense physical exertion and in the presence of other possible reasons for an increase in its activity; this can lead to misinterpretation of the results obtained. If the initial CPK activity is significantly exceeded (5 times higher than the ULN), a re-analysis should be performed after 5-7 days. It is impossible to start therapy if the results of repeated analysis confirm the initial high activity of CPK (more than 5-fold excess of ULN). Before starting therapy Depending on the daily dose in patients with existing risk factors for myopathy / rhabdomyolysis, rosuvastatin is either contraindicated or should be prescribed with caution (see "Contraindications", "Restrictions on use").
These factors include: impaired renal function; hypothyroidism; a history of muscle diseases (including in the family); a history of myotoxic events when taking other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; age over 65; conditions in which the concentration of rosuvastatin in blood plasma may increase; simultaneous use of fibrates. In such patients, it is necessary to assess the risk and possible benefits of therapy. Clinical monitoring is also recommended. If the initial activity of CPK is more than 5 times higher than that of VGN, rosuvastatin therapy cannot be started.
During the period of rosuvastatin therapy, the patient should be informed about the need for immediate medical attention in case of sudden onset of muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, the activity of CPK should be determined. Therapy should be discontinued if the CPK activity is significantly increased (more than 5 times compared to the ULN) or the muscle symptoms are pronounced and cause daily discomfort (even if the CPK activity is no more than 5 times higher than the ULN).
If symptoms disappear and CPK activity returns to normal, consideration should be given to resuming the use of rosuvastatin or other HMG-CoA reductase inhibitors in lower doses with close medical supervision. Controlling CPK activity in the absence of symptoms is inappropriate. There have been very rare cases of immune-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of the proximal muscles and an increase in the activity of CPK in the blood serum during therapy or upon discontinuation of the use of HMG-CoA reductase inhibitors, incl. rosuvastatin. Additional studies of the muscular and nervous system, serological studies, and therapy with immunosuppressive drugs may be required. There were no signs of an increase in the effect on skeletal muscles when taking rosuvastatin and concomitant therapy. However, an increase in the number of cases of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives (for example gemfibrozil), cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), antifungal derivatives azole, HIV protease inhibitors and macrolide antibiotics. When used simultaneously with some inhibitors of HMG-CoA reductase, gemfibrozil increases the risk of myopathy. Thus, the simultaneous use of rosuvastatin and gemfibrozil is not recommended. The benefits of further altering the plasma lipid concentration when combined with fibrates or nicotinic acid in lipid-lowering doses must be carefully weighed against the potential risk. Rosuvastatin at a dose of 30 mg / day is contraindicated for combination therapy with fibrates.
Due to the increased risk of rhabdomyolysis, rosuvastatin should not be used in patients with acute conditions that can lead to myopathy, or conditions that predispose to the development of renal failure (for example, sepsis, arterial hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disturbances or uncontrolled seizures). Liver. Depending on the daily dose, rosuvastatin is contraindicated or should be used with caution in patients with excessive alcohol consumption and / or with a history of liver disease (see "Contraindications", "Restrictions on use").
It is recommended to carry out the determination of liver function tests before starting therapy and 3 months after starting therapy. The use of rosuvastatin should be discontinued or the dose of this agent should be reduced if the activity of hepatic transaminases in the blood serum is 3 times higher than the ULN. In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy for the underlying diseases should be carried out before starting treatment with rosuvastatin. Ethnic characteristics.
In the course of pharmacokinetic studies in representatives of the Mongoloid race, an increase in the plasma concentration of rosuvastatin was noted in comparison with representatives of the Caucasian race. Interstitial lung disease. With the use of some HMG-CoA reductase inhibitors, especially for a long time, isolated cases of interstitial lung disease have been reported.
Symptoms include shortness of breath, unproductive cough, and deterioration in general well-being (weakness, weight loss, and fever). If interstitial lung disease is suspected, therapy with HMG-CoA reductase inhibitors should be discontinued. Type 2 diabetes mellitus. In patients with glucose concentrations ranging from 5.6 to 6.9 mmol / L, rosuvastatin therapy was associated with an increased risk of type 2 diabetes mellitus. Effects on the ability to drive or perform work requiring an increased speed of physical and mental reactions.
Studies to study the effect of rosuvastatin on the ability to drive vehicles and work with mechanisms have not been conducted. Nevertheless, given the possibility of dizziness and other side effects, care must be taken when driving vehicles and other mechanisms that require increased concentration of attention and speed of psychomotor reactions.
The incidence of serious renal dysfunction observed in post-marketing studies of rosuvastatin is higher with a dose of 40 mg / day. In patients taking the drug at a dose of 30 or 40 mg / day, it is recommended to monitor renal function indicators during treatment (at least once every 3 months). Influence on the musculoskeletal system.
When using rosuvastatin in all doses, but especially in doses exceeding 20 mg / day, the following effects on the musculoskeletal system have been reported: myalgia, myopathy, in rare cases, rhabdomyolysis. There have been very rare cases of rhabdomyolysis with the simultaneous use of HMG-CoA reductase inhibitors and ezetimibe. This combination should be used with caution as pharmacodynamic interaction cannot be excluded. As in the case of other HMG-CoA reductase inhibitors, the frequency of rhabdomyolysis with post-marketing use of rosuvastatin is higher with a dose of 40 mg / day
Determination of CPK activity. CPK activity cannot be determined after intense physical exertion and in the presence of other possible reasons for an increase in its activity; this can lead to misinterpretation of the results obtained. If the initial CPK activity is significantly exceeded (5 times higher than the ULN), a re-analysis should be performed after 5-7 days. It is impossible to start therapy if the results of repeated analysis confirm the initial high activity of CPK (more than 5-fold excess of ULN). Before starting therapy Depending on the daily dose in patients with existing risk factors for myopathy / rhabdomyolysis, rosuvastatin is either contraindicated or should be prescribed with caution (see "Contraindications", "Restrictions on use").
These factors include: impaired renal function; hypothyroidism; a history of muscle diseases (including in the family); a history of myotoxic events when taking other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; age over 65; conditions in which the concentration of rosuvastatin in blood plasma may increase; simultaneous use of fibrates. In such patients, it is necessary to assess the risk and possible benefits of therapy. Clinical monitoring is also recommended. If the initial activity of CPK is more than 5 times higher than that of VGN, rosuvastatin therapy cannot be started.
During the period of rosuvastatin therapy, the patient should be informed about the need for immediate medical attention in case of sudden onset of muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, the activity of CPK should be determined. Therapy should be discontinued if the CPK activity is significantly increased (more than 5 times compared to the ULN) or the muscle symptoms are pronounced and cause daily discomfort (even if the CPK activity is no more than 5 times higher than the ULN).
If symptoms disappear and CPK activity returns to normal, consideration should be given to resuming the use of rosuvastatin or other HMG-CoA reductase inhibitors in lower doses with close medical supervision. Controlling CPK activity in the absence of symptoms is inappropriate. There have been very rare cases of immune-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of the proximal muscles and an increase in the activity of CPK in the blood serum during therapy or upon discontinuation of the use of HMG-CoA reductase inhibitors, incl. rosuvastatin. Additional studies of the muscular and nervous system, serological studies, and therapy with immunosuppressive drugs may be required. There were no signs of an increase in the effect on skeletal muscles when taking rosuvastatin and concomitant therapy. However, an increase in the number of cases of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives (for example gemfibrozil), cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), antifungal derivatives azole, HIV protease inhibitors and macrolide antibiotics. When used simultaneously with some inhibitors of HMG-CoA reductase, gemfibrozil increases the risk of myopathy. Thus, the simultaneous use of rosuvastatin and gemfibrozil is not recommended. The benefits of further altering the plasma lipid concentration when combined with fibrates or nicotinic acid in lipid-lowering doses must be carefully weighed against the potential risk. Rosuvastatin at a dose of 30 mg / day is contraindicated for combination therapy with fibrates.
Due to the increased risk of rhabdomyolysis, rosuvastatin should not be used in patients with acute conditions that can lead to myopathy, or conditions that predispose to the development of renal failure (for example, sepsis, arterial hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disturbances or uncontrolled seizures). Liver. Depending on the daily dose, rosuvastatin is contraindicated or should be used with caution in patients with excessive alcohol consumption and / or with a history of liver disease (see "Contraindications", "Restrictions on use").
It is recommended to carry out the determination of liver function tests before starting therapy and 3 months after starting therapy. The use of rosuvastatin should be discontinued or the dose of this agent should be reduced if the activity of hepatic transaminases in the blood serum is 3 times higher than the ULN. In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy for the underlying diseases should be carried out before starting treatment with rosuvastatin. Ethnic characteristics.
In the course of pharmacokinetic studies in representatives of the Mongoloid race, an increase in the plasma concentration of rosuvastatin was noted in comparison with representatives of the Caucasian race. Interstitial lung disease. With the use of some HMG-CoA reductase inhibitors, especially for a long time, isolated cases of interstitial lung disease have been reported.
Symptoms include shortness of breath, unproductive cough, and deterioration in general well-being (weakness, weight loss, and fever). If interstitial lung disease is suspected, therapy with HMG-CoA reductase inhibitors should be discontinued. Type 2 diabetes mellitus. In patients with glucose concentrations ranging from 5.6 to 6.9 mmol / L, rosuvastatin therapy was associated with an increased risk of type 2 diabetes mellitus. Effects on the ability to drive or perform work requiring an increased speed of physical and mental reactions.
Studies to study the effect of rosuvastatin on the ability to drive vehicles and work with mechanisms have not been conducted. Nevertheless, given the possibility of dizziness and other side effects, care must be taken when driving vehicles and other mechanisms that require increased concentration of attention and speed of psychomotor reactions.
Storage conditions
Store in a dark place at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
Shelf life
2 years