Rozistark pills 20mg, 28pcs

Composition

of 1 tab. rosuvastatin calcium 20.8 mg, which corresponds to the content of rosuvastatin 20 mg

Auxiliary substances:

lactose monohydrate – 179.28 mg,

microcrystalline cellulose-85.37 mg,

crospovidone-12 mg,

magnesium stearate-2.55 mg.

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

Pharmacological action

Hypolipidemic agent from the statin group, HMG-CoA reductase inhibitor. According to the principle of competitive antagonism, the statin molecule binds to the part of the coenzyme A receptor where this enzyme is attached. Another part of the statin molecule inhibits the conversion of hydroxymethylglutarate to mevalonate, an intermediate in the synthesis of the cholesterol molecule. Inhibition of HMG-CoA reductase activity leads to a series of sequential reactions, which result in a decrease in the intracellular cholesterol content and a compensatory increase in the activity of LDL receptors and, accordingly, an acceleration of LDL cholesterol (Xc) catabolism.

The hypolipidemic effect of statins is associated with a decrease in the level of total cholesterol due to LDL-C. The decrease in LDL levels is dose-dependent and is not linear, but exponential.

Statins do not affect the activity of lipoprotein and hepatic lipases, do not significantly affect the synthesis and catabolism of free fatty acids, so their effect on TG levels is secondary and mediated through their main effects on lowering LDL-C levels. A moderate decrease in TG levels during statin treatment appears to be associated with the expression of remnant (apo E) receptors on the surface of hepatocytes involved in the catabolism of STDs, which comprise approximately 30% of TG.

In addition to the hypolipidemic effect, statins have a positive effect on endothelial dysfunction (a preclinical sign of early atherosclerosis), on the vascular wall, the state of atheroma, improve the rheological properties of blood, have antioxidant, antiproliferative properties.

The therapeutic effect manifests itself within 1 week after the start of therapy and after 2 weeks of treatment is 90% of the maximum possible effect, which is usually achieved by 4 weeks and remains constant after that.

Indications

— primary hypercholesterolemia (type IIa according to Fredrickson, including family heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb according to Fredrickson) as an adjunct to diet when diet and other non-pharmacological treatments (e. g. exercise, weight reduction) are insufficient;

homozygous form of familial hypercholesterolemia as an adjunct to diet and other Lipetskaya therapy (e. g., LDL apheresis) or if such therapy is not effective enough;

hypertriglyceridemia (type IV according to Fredrickson) as a Supplement to the diet;

— to slow the progression of atherosclerosis as an adjunct to diet in patients who have shown therapy to reduce the concentration of total Cholesterol and Cholesterol-LDL;

— reducing the risk of major cardiovascular complications (cardiovascular death, stroke, heart attack, unstable angina and arterial revascularization) in adult patients with the presence of high-risk cardiovascular complications of atherosclerosis (like increased concentration of C-reactive protein, age, hypertension, low concentration of HDL-C, Smoking or a family history of early CHD);

— primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease, but with an increased risk of its development (the age of 50 years for men and over 60 years for women, the increased concentration of C-reactive protein (>2 mg/l) in the presence of at least one additional risk factors such as arterial hypertension, a low concentration of HDL-C, Smoking, family history of early coronary heart disease).

Contraindications

— liver disease in the active phase, including a persistent increase in liver transaminases and any increase of transaminases in blood serum more than 3 times compared to the ULN;

— renal failure severe (CC

— myopathy;

— concomitant use of cyclosporine;

— patients predisposed to the development myotoxicity complications;

women of reproductive age not using reliable contraception;

— pregnancy;

— lactation (breastfeeding);

— age under 18 years (effectiveness and safety not established);

— lactose intolerance, lactase deficiency or glucose-galactose malabsorption (because the drug contains lactose);

— hypersensitivity to rosuvastatin or to any of the components of the drug.

With caution:

Risk of developing myopathy/rhabdomyolysis – renal failure, hypothyroidism; personal or family history of hereditary muscle diseases, a history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; conditions with increased plasma concentrations of rosuvastatin; age over 70 years; a history of liver disease; sepsis; hypotension; extensive surgical interventions * injuries; severe metabolic, endocrine or water-electrolyte disorders; uncontrolled epilepsy; race (Mongoloid race); simultaneous intake of fibrates.

Side effects

Side effects associated with taking Rosistark® are usually moderate and go away on their own. The frequency of side effects is mainly dose-dependent, as with other HMG-CoA reductase inhibitors.

To indicate the frequency of side effects, the following classification is used: often (>1/100 and 1/1000 and 1/10 000 and>

From the immune system:  rarely – hypersensitivity, including angioedema.

From the central nervous system:  often – headache, dizziness; very rarely-polyneuropathy, memory loss.

From the hematopoietic system:  unspecified frequency-thrombocytopenia.

From the digestive system:  often-constipation, nausea, abdominal pain; rarely-pancreatitis.

From the liver:  when using 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 minor, asymptomatic, and temporary.

From the endocrine system:  often – type 2 diabetes mellitus, thyroid disorders.

Musculoskeletal disorders:  often – myalgia; rarely-myopathy (including myositis), rhabdomyolysis; unspecified frequency-immune-mediated necrotizing myopathy.

Effects on skeletal muscles that cause myalgia, myopathy (including myositis) and, in rare cases, rhabdomyolysis with or without acute renal failure have been 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 insignificant, asymptomatic and temporary. In the case of an increase in CK activity by more than 5 times compared to ULN, therapy should be suspended.

From the urinary system:  when taking rosuvastatin, proteinuria may occur. Changes in the protein content in the urine (from the absence or presence of trace amounts to ++ and higher) are observed in less than 1% of patients taking rosuvastatin at a dose of 10 mg and 20 mg, and in approximately 3% of patients taking the drug at a dose of 40 mg. A slight change in the amount of protein in the urine, expressed in a change from zero or traces to+, was observed when taking the drug at a dose of 20 mg. In most cases, proteinuria decreased and passed independently during treatment. No causal association between proteinuria and acute or progressive kidney disease was found in the analysis of clinical trials.

From the side of the skin:  infrequently – skin pruritus, rash, urticaria.

From the side of the reproductive system and mammary glands:  unspecified frequency-gynecomastia.

Laboratory parameters:  increased concentration of glucose, bilirubin, GGT activity, alkaline phosphatase.

Other services:  often-asthenic syndrome; unspecified frequency-peripheral edema.

The following side effects have been reported with some statins: depression, sleep disorders including insomnia and nightmares, and sexual dysfunction.

Isolated cases of interstitial lung disease have been reported with prolonged use of rosuvastatin.

Interaction

Transport protein inhibitors:  rosuvastatin binds to some transport proteins, in particular, to OATP1 In 1 and OTP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in plasma and an increased risk of developing myopathy (see Table 1 and sections “Dosage and administration” and “Special Instructions”).

Cyclosporine:  when rosuvastatin and cyclosporine were co-administered, the AUC of rosuvastatin increased 7-fold compared to the values obtained in healthy volunteers. Combined use leads to an 11-fold increase in the concentration of rosuvastatin in blood plasma. Concomitant use of the drugs does not affect the concentration of cyclosporine in the blood plasma.

Vitamin K antagonists: as with other HMG-CoA reductase inhibitors, starting rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant indirect anticoagulants (for example, warfarin or other coumarin anticoagulants) may lead to an increase in prothrombin time and INR. Discontinuation of rosuvastatin or reduction of the dose may cause a decrease in INR. In such cases, INR should be monitored.

Ezetimibe: when rosuvastatin and ezetimibe are co-administered, there is no change in the AUC or Cmax of either drug.

Gemfibrozil and other lipid-lowering agents: simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax and AUC of rosuvastatin. Based on the data of the specific interaction study, no pharmacokinetically significant interaction with fenofibrate is expected, but a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates, and nicotinic acid in lipid-lowering doses (1 g or more per day) when co-administered with HMG-CoA reductase inhibitors increased the risk of myopathy, possibly due to the fact that they can cause myopathy and when used as monotherapy. Concomitant use of 40 mg of rosuvastatin and fibrates is contraindicated. When taking the drug simultaneously with gemfibrozil and other lipid-lowering agents at a dose of more than 1 g/day, the initial dose of Rozistark® should not exceed 5 mg.

HIV protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant use of rosuvastatin with HIV protease inhibitors may lead to a significant increase in rosuvastatin exposure. A pharmacokinetic study with simultaneous use of 20 mg of rosuvastatin and a combination drug containing two HIV protease inhibitors (400 mg of lopinavir/100 mg of ritonavir) in healthy volunteers revealed a 2-fold increase in AUC(0-24) and 5-fold Cmax of rosuvastatin. Therefore, concomitant use of rosuvastatin and HIV protease inhibitors in the treatment of patients with HIV is not recommended.

Antacids: concomitant use of rosuvastatin and antacid suspensions containing aluminum or magnesium hydroxide may lead to a decrease in the concentration of rosuvastatin in blood plasma by about 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin: concomitant use of rosuvastatin and erythromycin may lead to a decrease in AUC (0-t) rosuvastatin by 20% and rosuvastatin Cmax by 30%. Such an interaction may be caused by increased intestinal motility due to the intake of erythromycin.

Oral Contraceptives/Hormone replacement therapy:concomitant use of rosuvastatin and oral contraceptives may increase the AUC of ethinyl estradiol and norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be considered when choosing the dose of oral contraceptives. There are no pharmacokinetic data on the concomitant use of rosuvastatin and hormone replacement therapy, therefore, a similar effect cannot be excluded when using this combination. However, this combination of drugs was widely used in clinical trials and was well tolerated by patients.

Cytochrome P 450 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 rather 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). Current use of rosuvastatin and itraconazole (an inhibitor of the CYP3A4 isoenzyme) increases the AUC of rosuvastatin by 28% (clinically significant). Therefore, no drug interaction associated with cytochrome P450 metabolism is expected.

Other medicinal products: no clinically significant interaction is expected when rosuvastatin and digoxin are co-administered.

Drug interactions that require dose adjustment of rosuvastatin

Table 1. Effect of concomitant therapy on rosuvastatin exposure

Mode concomitant tarpeisiin reception rosuvastatina the AUC rosuvastatin 75-200 mg 2 times/day,6 months 10 mg 1 time/day,10 neuveritelne in 7.1 rajatanavin 300 mg/ritonavir 100 mg 1 time/day,8 days 10 mg odnocratno. sochetanie in 3.1 rosalpina 400 mg/ritonavir 100 mg 2 times/day,17 days,20 mg 1 time/day,7 neuveritelne in 2.1 resiential 600 mg 2 times/day,7 days 80 mg odnocratno. sochetanie in 1.9 resultaba 75 mg 1 time/day,10 days 10 mg odnocratno. sochetanie in 1.6 Roadrunner 600 mg/ritonavir 100 mg 2 times/day,7 days 10 mg 1 time/day,7 neuveritelne in 1.5 resetiranje 500 mg/ritonavir 200 mg 2 times/day,11 days 10 mg odnocratno. sochetanie in 1.4 risedronate 400 mg 2 times/will SATNET dennyhamlin in 1.4 researcher 200 mg 1 time/day,5 days 10 mg or 80 mg odnocratno. sochetanie 1.4 rathauseck 10 mg 1 time/day,14 days 10 mg 1 time/day,14 neuveritelne in 1.2 resetserver 700 mg/ritonavir 100 mg 2 times/day,8 days 10 mg onocrotalus essentialiter 0.3 mg,7 days 40 mg,7 dnases of izmeneniyami 140 mg 3 times/day,5 days 10 mg onocrotalus identifiziert 67 mg 3 times/day,7 days 10 mg,7 dnases of izmenenijami 450 mg 1 time/day,7 days 20 mg onocrotalus identications 200 mg 2 times/day,7 days 80 mg onocrotalus identiflyer 200 mg 1 time/day,11 days 80 mg onocrotalus essentialtravel 500 mg 4 times/day,7 days 80 mg odnocratno. sochetanie 28%Baicalin 50 mg 3 times/day,14 days 20 mg odnocratno. sochetanie 47%

How to take, course of use and dosage

The drug is taken orally. The tablet should be swallowed whole, washed down with water, without chewing or grinding. The drug can be taken at any time of the day, regardless of food intake.

Before starting treatment, the patient should begin to follow a diet with low cholesterol products, which should be continued throughout the entire treatment period.

The dose of the drug should be selected individually, depending on the goals of therapy and response to treatment, taking into account current generally accepted recommendations for target lipid concentrations.

If it is necessary to use the drug at 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 a risk (a tablet at a dose of 10 mg should be divided into two parts according to risk).

The recommended starting dose of the drug is 5 mg or 10 mg 1 time/day for both patients who have not previously taken statins, and for patients transferred to the use of this drug after therapy with other HMG-CoA reductase inhibitors. When choosing the initial dose, the cholesterol level in each individual patient should be taken into account and the possible risk of cardiovascular complications should be taken into account, as well as the potential risk of side effects should be assessed. If necessary, the dose can be increased after 4 weeks.

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 to a maximum dose of 40 mg for 4 weeks of therapy can only be carried out in patients with severe hypercholesterolemia and at high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia), who did not achieve the desired effect of therapy when using the drug at a dose of 20 mg, and who will be under medical supervision.

When prescribing the drug at a dose of 40 mg, careful monitoring of the patient is recommended. It is not recommended to prescribe the drug at a dose of 40 mg to patients who have not previously consulted a doctor.

After 2-4 weeks of therapy and/or when increasing the dose of the drug, it is necessary to monitor the parameters of lipid metabolism, if necessary, the dose should be adjusted.

The dose of the drug should be adjusted if it is necessary to use it together with drugs that increase the exposure of rosuvastatin. If exposure is expected to increase by a factor of 2 or more, the initial dose of the drug should be 5 mg 1 time / day. It is also necessary to adjust the maximum daily dose of the drug so that the expected exposure of rosuvastatin does not exceed that for a dose of 40 mg taken without simultaneous use of drugs that interact with rosuvastatin (see the section “Interaction with other drugs” Table 1).

Elderly patients do not require dose adjustment.

No dose adjustment is required in patients with mild or moderate renal insufficiency. In patients with severe renal insufficiency (CC

The drug is contraindicated in patients with liver diseases in the active phase.

In patients of the Mongolian 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 Mongolian 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.

Overdose

There is no specific therapy for rosuvastatin overdose.

In case of overdose, it is recommended to carry out symptomatic treatment and measures that support the functions of vital organs and systems.

Liver function and CKD activity should be monitored. Hemodialysis is probably ineffective in this case.

Special instructions

Kidneys

Proteinuria, mainly of tubular origin, was observed in patients receiving high doses of rosuvastatin, especially 40 mg, which in most cases was intermittent or short-term. Such proteinuria does not mean the occurrence of acute or progressive kidney disease. The incidence of serious renal impairment increases with 40 mg of rosuvastatin. In these patients, monitoring of renal function is recommended during treatment with Rosistark®.

Musculoskeletal system

Myalgia, myopathy and, in rare cases, rhabdomyolysis have been reported when Rosistark® is used in all dosages, and especially when the drug is taken at a dose exceeding 20 mg. In very rare cases, rhabdomyolysis has occurred when ezetimibe and HMG-CoA reductase inhibitors were co-administered. In this case, the pharmacological effects of drugs cannot be excluded, so these drugs should be used with caution at the same time. When taking Rozistark® at a dose of 40 mg, the incidence of rhabdomyolysis increases.

Determination of CKD activity

Determination of CKD activity should not be performed after intense physical activity or in the presence of other possible causes of increased CKD activity, which may lead to misinterpretation of the results. If the initial CPK level is significantly elevated (more than 5 times higher than ULN), then a second measurement should be performed after 5-7 days. Do not start therapy if repeated measurement confirms the initial CPK level (5 times higher than ULN).

Before starting 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 of personal or family history of muscle diseases (for a dose of 40 mg);

— note in the history of myotoxicity in patients receiving other inhibitors of HMG-COA reductase inhibitors or fibrates (for a dose of 40 mg);

— alcohol (for a dose of 40 mg);

— age over 70 years;

— state, accompanied by an increase in the concentration of the drug in the blood plasma (for a dose of 40 mg);

— concurrent use of fibrates (for doses of 40 mg).

In such patients, the risk-benefit ratio of therapy should be evaluated and clinical monitoring 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 about cases of unexpected muscle pain, muscle weakness or spasms, especially in combination with malaise or fever. In such patients, CPK activity should always be monitored. Treatment should be discontinued if CPK activity is more than 5 times higher than ULN or if muscle symptoms are severe and cause daily discomfort, even if CPK activity is 5 times lower than ULN. If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Rozistark® or other HMG-CoA reductase inhibitors in smaller doses, with careful monitoring of the patient. Regular monitoring of CKD 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 increased activity of CPK in the blood serum have been noted during treatment or upon discontinuation of statins, including rosuvastatin. Additional studies of the muscular and nervous systems, serological studies, and immunosuppressive therapy may be required.

There were no signs of increased effects on skeletal muscle with rosuvastatin and concomitant therapy. However, an increase in 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 macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Therefore, simultaneous use of rosuvastatin and gemfibrozil is not recommended. The risk-benefit ratio should be carefully evaluated when rosuvastatin is co-administered with fibrates or nicotinic acid in lipid-lowering doses (more than 1 g/day). Concomitant use of rosuvastatin at a dose of 40 mg and fibrates is contraindicated. In 2-4 weeks after the start of treatment and/or when increasing the dose of Rosistark®, monitoring of lipid metabolism parameters is necessary, if necessary, dose adjustment is required.

Do not prescribe the drug to patients with acute, severe diseases that suggest myopathy, or with the possible development of secondary renal failure (for example, sepsis, arterial hypertension, surgery, trauma, metabolic syndrome, seizures, endocrine disorders, water and electrolyte disorders).

The liver

Like other HMG-CoA reductase inhibitors, Rosistark® should be used with extreme caution in patients who abuse alcohol or have a history of liver disease. It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. If the activity of hepatic transaminases in the blood serum is 3 times higher than the ULN, you should stop taking Rosistark® or reduce the dose of the drug. The frequency of severity of liver function disorders, mainly associated with increased activity of hepatic transaminases, increases when taking 40 mg of the drug.

In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the underlying disease should be treated before starting treatment with rosuvastatin.

Ethnic groups

Pharmacokinetic studies revealed an increase in the systemic concentration of rosuvastatin among patients of Chinese and Japanese origin compared to the indicators obtained among patients of the Caucasian race.

HIV protease inhibitors

Concomitant use of rosuvastatin with HIV protease inhibitors is not recommended.

Lactose

Do not use the drug in patients with lactase deficiency, galactose intolerance and glucose-galactose malabsorption.

Interstitial lung disease

Isolated cases of interstitial lung disease have been reported with the use of certain statins, especially for a long time. Symptoms of the disease may include shortness of breath, dry cough, and poor overall health (weakness, weight loss, and fever). If interstitial lung 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 developing type 2 diabetes.

Influence on the ability to drive motor vehicles and manage mechanisms

Studies on 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 should be borne in mind that dizziness may occur during treatment.

Form of production

Tablets, film-coated from light yellow to yellow in color, round, biconvex, with the inscription “20” on one side and ” 15 ” on the other side.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Expiration date

Shelf life-3 years.

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets