Description
Release form
Film-coated tablets from light yellow to yellow in color, round, biconvex, engraved with 20 on one side and 15 on the other side.
Pharmacological action of
A hypolipidemic agent from the statins group, an inhibitor of HMG-CoA reductase inhibitor. According to the principle of competitive antagonism, a statin molecule binds to that part of the coenzyme A receptor where this enzyme attaches. Another part of the statin molecule inhibits the conversion of hydroxymethylglutarate to mevalonate, an intermediate in the synthesis of cholesterol molecules. Inhibition of the activity of HMG-CoA reductase leads to a series of sequential reactions, resulting in a decrease in the intracellular cholesterol content and a compensatory increase in the activity of LDL receptors and, accordingly, accelerated catabolism of LDL cholesterol (Xc).
The hypolipidemic effect of statins is associated with a decrease in total cholesterol due to LDL cholesterol. The decrease in LDL is dose-dependent and is not linear, but exponential.
Statins do not affect the activity of lipoprotein and hepatic lipases, do not have a significant effect on the synthesis and catabolism of free fatty acids, therefore, their effect on the level of TG is secondary and indirectly through their main effects on reducing the level of LDL-C. A moderate decrease in the level of TG during treatment with statins is apparently associated with the expression of remnant (apo E) receptors on the surface of hepatocytes involved in catabolism of STDs, which comprise about 30% TG.
In addition to lipid-lowering effects, statins have a positive effect on endothelial dysfunction (preclinical sign of early atherosclerosis), on the vascular wall, atheroma state, improve blood rheological properties, have antioxidant, antiproliferative properties.
The therapeutic effect appears within 1 week. after the start of therapy and after 2 weeks of treatment is 90% of the maximum possible effect, which is usually reached by 4 weeks and after that remains constant.
Indications
– primary hypercholesterolemia (type IIa according to Fredrickson, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb according to Fredrickson) as a supplement to the diet, when diet and other non-medications, e.g. weight loss) are insufficient
– a homozygous form of hereditary hypercholesterolemia as a supplement to diet and other lipid lowering therapy (for example, LDL apheresis) or in cases where such therapy is not effective enough
– hypertriglyceridemia (type IV Fredrickson) as an adjunct
diet – to slow the progression of atherosclerosis as a supplement to the diet in patients who are shown therapy to reduce the concentration of total Chs and LDL-Cs
– reducing the risk of underlying heart cardiovascular complications (cardiovascular death, stroke, heart attack, unstable angina and arterial revascularization) in adult patients with risk factors for cardiovascular complications of atherosclerosis (such as increased concentration of C-reactive protein, age, arterial hypertension, low concentration of HDL cholesterol, smoking and a family history of early onset of coronary heart disease)
– primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary artery disease, but with an increased risk of its development (age over 50 for men and over 60 for women, increased concentration of C-reactive protein (> 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low concentration I XC-HDL cholesterol, smoking, family history of coronary artery disease early development).
Contraindications
– active phase liver disease, including a persistent increase in hepatic transaminase activity and any increase in serum transaminase activity by more than 3 times in comparison with HBV
– severe renal failure (CC
– myopathy
ri –
– patients predisposed to the development of myotoxic complications
– women of reproductive age who do not use reliable contraceptives
– pregnancy
– lactation (gru breastfeeding)
– age up to 18 years (efficacy and safety have not been established)
– lactose intolerance, lactase deficiency or glucose-galactose malabsorption (since the drug contains lactose)
– hypersensitivity to rosuvastatin or any of the components of the drug.
Precautions:
Presence of a risk of myopathy / rhabdomyolysis – renal failure, hypothyroidism, personal or family history of hereditary muscle disease, history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates, excessive use of alcohol, which noted an increase in plasma concentration of rosuvastatin over the age of 70 years of liver disease in the history of sepsis arterial hypotension extensive surgical interventions of herbs we are heavy metabolic endocrine or water-electrolyte disturbances uncontrolled epilepsy race (Mongoloid race) simultaneous administration of fibrates.
Use during pregnancy and lactation
Rosistark ® is contraindicated in pregnancy and during breastfeeding.
Women of reproductive age should use reliable and appropriate methods of contraception.
Since cholesterol and other cholesterol biosynthesis products are important for the development of the fetus, the potential risk of inhibiting HMG-CoA reductase exceeds the benefits of using the drug in pregnant women.
If a pregnancy is diagnosed during treatment, the drug should be discontinued immediately.
There are no data on the allocation of rosuvastatin with breast milk, therefore, during the period of breastfeeding, the drug should be discontinued.
Special instructions
Kidney
Proteinuria, mainly of tubular origin, was observed in patients taking rosuvastatin in high doses, in particular 40 mg, which in most cases was periodic or short-term. Such proteinuria does not mean the occurrence of acute or progressive kidney disease. The frequency of serious renal impairment increases with 40 mg of rosuvastatin. In such patients, it is recommended to monitor renal function indicators during treatment with Rosistark ®.
Musculoskeletal system
When using Rosistark ® in all dosages, and especially when taking the drug in a dose exceeding 20 mg, myalgia, myopathy and, in rare cases, rhabdomyolysis were detected. In very rare cases, rhabdomyolysis occurred while taking ezetimibe and HMG-CoA reductase inhibitors. In this case, the pharmacological effects of the drugs cannot be ruled out, therefore, these drugs should be used with caution at the same time. When taking Rosistark ® at a dose of 40 mg, the incidence of rhabdomyolysis increases.
Determination of CPK activity
Determination of CPK activity should not be carried out after intense physical exertion or if there are other possible reasons for the increase in CPK activity, which may lead to an incorrect interpretation of the results. If the initial level of CPK is significantly increased (more than 5 times higher than VGN), then after 5-7 days, a second measurement should be carried out. Therapy should not be started if a repeated measurement confirms the initial level of CK (5 times higher compared with VGN).
Prior to
therapy, Rosistark ®, like other HMG-CoA reductase inhibitors, should be used with caution in patients with existing risk factors for myopathy / rhabdomyolysis. These factors include:
– renal failure
– hypothyroidism (for a dose of 40 mg)
– an indication in the personal or family history of muscle diseases (for a dose of 40 mg)
– an indication of a history of myotoxicity while taking other inhibitors of HMG-CoA reductase or fiber (for a dose of 40 mg)
– alcohol abuse (for a dose of 40 mg)
– age older than 70 years
– conditions accompanied by an increase in the concentration of the drug in blood plasma (for a dose of 40 mg)
– concomitant use of fibrates (for a dose of 40 mg) .
In such patients, the ratio of risk and the possible benefits of therapy should be assessed and clinical observation should be carried out throughout the course of treatment.
During
therapy, it is recommended that patients be informed of the need to immediately inform the doctor of cases of sudden onset of muscle pain, muscle weakness, or cramping, especially in combination with malaise or fever. In such patients, it is imperative to monitor the activity of CPK. Treatment should be discontinued if the activity of CPK is more than 5 times higher than VGN or if the symptoms on the part of the muscles are pronounced and cause daily discomfort, even if the activity of KFK is 5 times lower than VGN. If symptoms disappear, and CPK activity returns to normal, consideration should be given to re-prescribing Rosistark ® or other HMG-CoA reductase inhibitors in lower doses with careful monitoring of the patient. Regular monitoring of CPK activity in the absence of symptoms is impractical.
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 treatment or when stopping statins, including rosuvastatin. Additional studies of the muscle and nervous systems, serological studies, as well as immunosuppressive therapy may be required.
No evidence of increased effects on skeletal muscle with rosuvastatin and concomitant therapy. However, an increase in cases of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors together with fibroic acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid, antifungal drugs, protease inhibitors and antibiotics from the macrolide group. Gemfibrozil increases the risk of myopathy when used together with certain HMG-CoA reductase inhibitors. Therefore, the simultaneous administration of rosuvastatin and gemfibrozil is not recommended. The risk-to-benefit ratio should be carefully assessed with the combined use of rosuvastatin with fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day). The concomitant use of rosuvastatin in a dose of 40 mg and fibrates is contraindicated. 2-4 weeks after the start of treatment and / or with an increase in the dose of Rosistark ®, monitoring of lipid metabolism is necessary, if necessary, dose adjustment is required.
The drug should not be prescribed to patients with acute, severe illnesses suggesting myopathy, or with the possible development of secondary renal failure (e.g., sepsis, arterial hypertension, surgery, trauma, metabolic syndrome, convulsions, endocrine disorders, water-electrolyte disturbances).
Liver
Like other HMG-CoA reductase inhibitors, Rosistark ® should be used with extreme caution in patients with a history of alcohol abuse or a history of liver disease. It is recommended to determine the liver function indicators before the start of therapy and 3 months after the start of therapy. If the activity of hepatic transaminases in blood serum is 3 times higher than VGN, you should stop taking Rosistark ® or reduce the dose of the drug. The frequency of severity of impaired liver function, associated mainly with an increase in the activity of hepatic transaminases, increases when taking 40 mg of the drug.
In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying disease should be carried out before treatment with rosuvastatin.
Ethnic groups
Pharmacokinetic studies have revealed an increase in systemic concentrations of rosuvastatin among patients of Chinese and Japanese origin compared with those obtained among patients of the Caucasian race.
HIV protease inhibitors
Concomitant use of rosuvastatin with HIV protease inhibitors is not recommended.
Lactose
The drug should not be used in patients with lactase deficiency, galactose intolerance and glucose-galactose malabsorption.
Interstitial pulmonary disease
With the use of certain statins, especially for a long time, isolated cases of interstitial pulmonary disease have been reported. Manifestations of the disease can include shortness of breath, dry cough, and a deterioration in overall well-being (weakness, weight loss, and fever). If interstitial pulmonary disease is suspected, statin therapy should be discontinued.
Diabetes mellitus
For patients with a glucose concentration of 5.6 to 6.9 mmol / L, the use of rosuvastatin leads to an increased risk of type 2 diabetes.
Influence on the ability to drive vehicles and control mechanisms
Studies to study the effect of rosuvastatin on the ability to drive vehicles and mechanisms have not been conducted. Based on the pharmacodynamic properties of the drug, it can be assumed that rosuvastatin should not have such an effect, however, it must be taken into account that dizziness may occur during treatment.
Composition
1 tab. rosuvastatin calcium 20.8 mg, which corresponds to the content of rosuvastatin 20 mg
Excipients:
lactose monohydrate – 179.28 mg,
microcrystalline cellulose – 85.37 mg,
crospovidone – 12 mg,
magnesium 2. mg stear.
Shell composition:
lactose monohydrate – 3. 6 mg,
hypromellose – 2.52 mg,
titanium dioxide – 2.1555 mg,
triacetin – 0.72 mg,
quinoline yellow – 0.0045 mg.
Dosage and administration of
The drug is taken orally. The tablet should be swallowed whole, washed down with water, without chewing or crushing. The drug can be taken at any time of the day, regardless of food intake.
Before starting treatment, the patient should start a diet with low cholesterol products, which should be continued throughout the treatment period.
The dose of the drug should be selected individually depending on the goals of therapy and the response to treatment, taking into account current generally accepted recommendations for target lipid concentrations.
If it is necessary to use the drug in a dose of 5 mg, it is recommended to use rosuvastatin in a different dosage form or dosage, for example, 5 mg tablets or 10 mg tablets with risk (10 mg tablet should be divided into two parts at risk).
The recommended initial dose of the drug is 5 mg or 10 mg 1 time / day for patients who have not previously taken statins, and for patients transferred to the use of this drug after treatment with other inhibitors of HMG-CoA reductase. When choosing an initial dose, one should take into account the level of cholesterol in each individual patient and take into account the possible risk of cardiovascular complications, as well as assess the potential risk of side effects. If necessary, after 4 weeks the dose can be increased.
Due to the possible development of side effects when using the drug at a dose of 40 mg, compared with lower doses of the drug, titration up to a maximum dose of 40 mg during 4 weeks of therapy can only be performed in patients with severe hypercholesterolemia and with a high risk of cardio -vascular complications (especially in patients with hereditary hypercholesterolemia), in which when using the drug in a dose of 20 mg, the desired effect of therapy was not achieved, and which will be under the supervision of a doctor.
When prescribing the drug in a dose of 40 mg, careful monitoring of the patient is recommended. The administration of the drug in a dose of 40 mg is not recommended for 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, monitoring of lipid metabolism is necessary, if necessary, the dose should be adjusted.
The dose of the drug should be adjusted if necessary, its combined use with drugs that increase the exposure of rosuvastatin. If an increase in exposure of 2 times or more is expected, the initial dose of the drug should be 5 mg 1 time / day. You should also adjust the maximum daily dose of the drug so that so that the expected exposure of rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs that interact with rosuvastatin (see Interaction with other drugs, see Table 1).
Elderly patients do not require dose adjustment.
In patients with mild or moderate renal failure, dose adjustment is not required. In patients with severe renal insufficiency (CC
The drug is contraindicated in patients with active liver disease.
In patients of the Mongoloid race, an increase in the systemic concentration of rosuvastatin is possible. This fact should be taken into account when prescribing the drug to these groups of patients. When prescribing the drug in doses of 10 mg and 20 mg, the recommended initial dose of the drug for patients of the Mongoloid race is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.
When prescribing the drug in doses of 10 mg and 20 mg, the recommended initial dose for patients with a predisposition to myopathy is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.
Side effects
Side effects associated with taking Rosistark ® are usually mild and go away on their own. The incidence of side effects is mainly dose-dependent in nature, as with other HMG-CoA reductase inhibitors.
The following classification is used to indicate the incidence of side effects: often (> 1/100 and 1/1000 and 1/10 000 and
On the part of the immune system: rarely – hypersensitivity, including angioedema.
From the side of the central nervous system: often – headache, dizziness very rarely – polyneuropathy, memory loss.
From the hemopoietic system: unspecified frequency – thrombocytopenia.
From the digestive system: often – constipation, nausea, abdominal pain rarely – pancreatitis.
From the liver: with the use of rosuvastatin, a dose-dependent increase in the activity of hepatic transaminases is observed in a small number of patients. In most cases, this increase is insignificant, asymptomatic and temporary.
From the endocrine system: often – type 2 diabetes mellitus, thyroid dysfunction.
From the musculoskeletal system: often – myalgia rarely – myopathy (including myositis), rhabdomyolysis of unspecified frequency – immuno-mediated necrotizing myopathy.
The effect on skeletal muscles that cause myalgia, myopathy (including myositis) and, in rare cases, rhabdomyolysis with or without the development of acute renal failure, was observed in patients taking any dose of rosuvastatin, especially when taking doses exceeding 20 mg. A dose-dependent increase in CPK activity was detected in patients taking rosuvastatin, but in most cases these manifestations were minor, asymptomatic and temporary. In the case of an increase in CPK activity by more than 5 times compared with VGN, therapy should be suspended.
From the urinary system: when taking rosuvastatin, proteinuria may be observed. Changes in urine protein content (from the absence or presence of trace amounts to ++ or higher) are observed in less than 1% of patients taking rosuvastatin at a dose of 10 mg and 20 mg, and in about 3% of patients taking the drug at a dose of 40 mg . A slight change in the amount of protein in the urine, expressed as a change from zero level or the presence of traces to level +, was observed when taking the drug at a dose of 20 mg. In most cases, proteinuria decreased and passed independently during treatment. An analysis of clinical trial data did not reveal a causal relationship between proteinuria and acute or progressive kidney disease.
From the skin: infrequently – itching, rash, urticaria.
From the reproductive system and mammary glands: unspecified frequency – gynecomastia.
Lab performance: increased concentration of glucose, bilirubin, activity of GGT, alkaline phosphatase.
Other: often – asthenic syndrome of unspecified frequency – peripheral edema.
The following side effects have been reported with some statins: depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction.
With prolonged use of rosuvastatin, isolated cases of interstitial lung disease have been reported.
Drug interactions
Transport protein inhibitors: rosuvastatin binds to certain transport proteins, in particular, OATP1B1 and BCRC. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in plasma concentration of rosuvastatin and an increased risk of myopathy (see Table 1 and sections Dosage and administration and special instructions).
Cyclosporine: with the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin increased by 7 times compared with the values obtained from healthy volunteers. Joint use leads to an increase in the concentration of rosuvastatin in blood plasma by 11 times. The simultaneous use of drugs does not affect the concentration of cyclosporine in blood plasma.
Vitamin K antagonists: as is the case with other HMG-CoA reductase inhibitors, initiating rosuvastatin therapy or increasing the dose in patients receiving simultaneously indirect anticoagulants (e.g. warfarin or other coumarin anticoagulants) can lead to an increase in prothrombin time and INR. Withdrawal of rosuvastatin or dose reduction may cause a decrease in INR. In such cases, an INR should be monitored.
Ezetimibe: with the simultaneous use of rosuvastatin and ezetimibe, there is no change in AUC or Cmax of both drugs.
Gemfibrozil and other lipid-lowering drugs: the simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax and AUC of rosuvastatin. Based on the data of the study of specific interaction, no pharmacokinetically significant interaction with fenofibrate is expected, but pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates, and nicotinic acid in lipid lowering doses (1 g or more per day) while using with HMG-CoA reductase inhibitors increased the risk of myopathy, possibly due to the fact that they can also cause myopathy when used as monotherapy. Concomitant use of 40 mg of rosuvastatin and fibrates is contraindicated. With the simultaneous administration of the drug with gemfibrozil and other lipid-lowering drugs in a dose of more than 1 g / day, the initial dose of the drug RosistArc ® should not exceed 5 mg.
HIV protease inhibitors: Although the exact mechanism of interaction is unknown, concurrent administration of rosuvastatin with HIV protease inhibitors can lead to a significant increase in the exposure of rosuvastatin. In a pharmacokinetic study, while taking 20 mg of rosuvastatin and a combination drug containing two HIV protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir) in healthy volunteers, a 2-fold increase in AUC (0-24) and a 5-fold Cmax of rosuvastatin were revealed. Therefore, the simultaneous administration of rosuvastatin and HIV protease inhibitors in the treatment of HIV patients is not recommended.
Antacids: concomitant use of rosuvastatin and suspensions of antacids containing aluminum or magnesium hydroxide can lead to a decrease in the concentration of rosuvastatin in blood plasma 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: concomitant use of rosuvastatin and erythromycin can lead to a decrease in AUC (0-t) of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. Such an interaction can be caused by increased intestinal motility due to the administration of erythromycin.
Oral contraceptives / hormone replacement therapy: concomitant use of rosuvastatin and oral contraceptives can lead to an increase in AUC of ethinyl estradiol and norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be considered when choosing a dose of oral contraceptives. There are no pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy, therefore, a similar effect cannot be ruled out when using this combination. However, this combination of drugs was widely used in clinical trials and was well tolerated by patients.
Cytochrome P450 isoenzymes: the results of in vitro and in vivo studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a fairly weak substrate for these isoenzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes). The current use of rosuvastatin and itraconazole (an inhibitor of the CYP3A4 isoenzyme) increases the AUC of rosuvastatin by 28% (clinically significant). Therefore, any drug interaction associated with the metabolism of cytochrome P450 is not expected.
Other medicines: no clinically significant interaction is expected with the simultaneous use of rosuvastatin and digoxin.
Interaction with drugs that require dose adjustment of rosuvastatin
Table 1. Effect of concomitant therapy on exposure to rosuvastatin
Concomitant therapy regimen Rosuvastatin regimen Change in AUC of rosuvastatin
Cyclosporine 75-200 mg 2 times / day, 6 months 10 mg 1 time , 10 days 7.1-fold increase in
Atazanavir 300 mg / ritonavir 100 mg 1 time / day, 8 days 10 mg once 3-fold increase. 1 time
Lopinavir 400 mg / ritonavir 100 mg 2 times / day, 17 days 20 mg 1 time / day, 7 days Increase 2.1 times
Gemfibrozil 600 mg 2 times / day, 7 days 80 mg once 1.9 times increase
Eltrombopag 75 mg 1 time / day, 10 days 10 mg once a 1.6-fold increase
Darunavir 600 mg / ritonavir 100 mg 2 times / day, 7 days 10 mg 1 time / day, 7 days 1.5-fold increase
Tipranavir 500 mg / ritonavir 200 mg 2 times / day, 11 days 10 mg one-time increase 1.4 times
Dronedarone 400 mg 2 times / day no data 1.4-fold increase
Itraconazole 200 mg 1 time / day, 5 days 10 mg or 80 mg once 1.4 times increase
Ezetimibe 10 mg 1 time / day, 14 days 10 mg 1 time / day, 14 days Increase 1.2 times
Fosamprenavir 700 mg / ritonavir 100 mg 2 times / day, 8 days 10 mg once Unchanged
Aleglitazar 0.3 mg 7 days 40 mg, 7 days No change
Silymarin 140 mg 3 times / day, 5 days 10 mg once No change
Fenofibrate 67 mg 3 times / day, 7 days 10 mg, 7 days No change
Rifampin 450 mg 1 time / day, 7 days 20 mg once Unchanged
Ketoconazole 200 mg 2 times / day, 7 days 80 mg once Unchanged
Fluconazole 200 mg 1 time / day, 11 days 80 mg once Unchanged
Erythromycin 500 mg 4 times / day, 7 days 80 mg once Reduced by 28%
Baikalin 50 mg 3 times / day, 14 days 20 mg once Reduced by 47%
Overdose of
specific therapy for an overdose of rosuvastatin does not exist.
In case of overdose, symptomatic treatment and supporting functions of vital organs and systems of the event are recommended.
Liver function and CPK activity should be monitored. Hemodialysis in this case is probably ineffective.
Storage Conditions
The product should be stored out of the reach of children at a temperature not exceeding 25 ° C.
Expiration
Expiration is 3 years.
active substance
Rosuvastatin
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