Ro-statin capsules 10mg, 30pcs

Composition

Active ingredient:  rosuvastatin calcium – 10,420 mg, in terms of rosuvastatin -10,000 mg. Auxiliary substances: lactose monohydrate (milk sugar) -140,658 mg; microcrystalline cellulose -24,614 mg; croscarmellose sodium-9,154 mg; povidone-K 25 -5,274 mg;colloidal silicon dioxide -1,940 mg; magnesium stearate-1,940 mg. Capsule body composition:  iron oxide black dye – 0.05%, titanium dioxide-2%, gelatin up to 100%. Capsule cap composition:  iron oxide yellow dye – 0.1%, titanium dioxide-2%, gelatin up to 100%.

Pharmacological action

Mechanism of action Rosuvastatin is a selective, competitive inhibitor of GM G-CoAg reductase, an enzyme that converts Z-hydroxy-Z-methylglutaryl coenzyme A to mevalonate, a cholesterol precursor. The main target of rosuvastatin action is the liver, where the synthesis of cholesterol (cholesterol) and catabolism of low-density lipoproteins (LDL) is carried out. Rosuvastatin increases the number of “hepatic” LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of very low-density lipoprotein (VLDL) synthesis, thereby reducing the total amount of LDL and VLDL. Pharmacodynamics Rosuvastatin reduces elevated concentrations of LDL cholesterol (LDL-C), total cholesterol, triglycerides (GH), increases the concentration of high-density lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (apoB), HDL-C, VLDL-C, VLDL-TG and increases the level of apolipoprotein A-I (ApoA-1), reduces the ratio of LDL/HDL cholesterol, total cholesterol/HDL cholesterol and non-HDL/HDL cholesterol, and the apoB/ApoA-1 ratio. The therapeutic effect appears within one week after starting therapy with Ro-statin, after 2 weeks of treatment it reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by the 4th week and is maintained with regular use of the drug. Clinical efficacy Rosuvastatin is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender or age, including in patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia of Ha and lib type according to the Fredrickson classification (the average initial concentration of LDL-C is about 4.8 mmol/l) against the background of taking the drug at a dose of 10 mg, the concentration of LDL-C reaches values of less than 3 mmol/l. In patients with heterozygous familial hypercholesterolemia receiving rosuvastatin at a dose of 20-80 mg, a positive dynamics of lipid profile indicators is noted. After titration to a daily dose of 40 mg (12 weeks of therapy), the LDL-C concentration decreased by 53%. In patients with homozygous familial hypercholesterolemia, taking rosuvastatin at a dose of 20 mg and 40 mg, the average decrease in LDL-C concentration is 22%. An additive effect is observed in combination with fenofibrate in relation to the concentration of triglycerides and with nicotinic acid in lipid-lowering doses (more than 1 g / day)in relation to the concentration of HDL-C.

Indications

• Fredrickson’s primary hypercholesterolemia (type Ha, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type lib) as an adjunct to diet when diet and other non-drug treatments (such as exercise, weight loss) are insufficient.

• Familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (for example, LDL apheresis), or in cases where such therapy is not effective enough.

• Hypertriglyceridemia (Fredrickson type IV) as a dietary supplement.

• To slow the progression of atherosclerosis as an adjunct to diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL-C.

• Primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), but with an increased risk of its development (age over 50 years for men and over 60 years 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 HDL-C concentration, smoking, family history of early

Contraindications

• hypersensitivity to rosuvastatin or to any component of the drug;

• liver disease in the active phase, including a persistent increase in serum transaminases and any increase of transaminases in blood serum (more than 3 times compared with the upper limit of normal);

• severe impairment of renal function (QC less than 30 ml/min);

• myopathy;

• concomitant use of cyclosporine;

• childhood and adolescence to 18 years;

• in women: pregnancy, breastfeeding, lack of adequate methods of contraception;

• patients predisposed to the development of myotoxicity complications; lactose intolerance, lactase deficiency or glucose-galactose malabsorption (product contains lactose).

With caution

• The risk of myopathy/rhabdomyolysis, renal failure, hypothyroidism, personal or family history of hereditary muscular diseases and previous history of muscular toxicity with the use of other inhibitors of HMG-COA reductase inhibitors or fibrates;

• excessive alcohol use;

• age over 65 years;

• a condition in which increased plasma concentrations of rosuvastatin;

• race (Mongoloid race);

• simultaneous use with fibrates; 

• a history of liver disease; 

• sepsis;

• hypotension;

• extensive surgery, trauma, severe metabolic, endocrine, or electrolyte disturbances, or uncontrolled seizures.

Side effects

Side effects observed when taking rosuvastatin are usually mild and go away on their own. As with other HMG-CoA reductase inhibitors, the frequency of side effects is dose-dependent. The frequency of occurrence of undesirable effects is presented as follows, according to the WHO classification:  Often (>1/100, ><1/10); Infrequently (>1/1000, <1/10); Infrequently (><1/100); Rarely (>1/10 000, <1/100); Rarely (><1/1000); Very rarely ( Immune system Rarely: hypersensitivity reactions, including angioedema Endocrine disorders Common: type 2 diabetes mellitus. From the central nervous system Often: headache, dizziness From the digestive tract Often: constipation, nausea, abdominal pain Rarely: pancreatitis From the side of the skin Infrequently: pruritus, rash, urticaria br> Musculoskeletal disorders Common: myalgia Rare: myopathy (including myositis), rhabdomyolysis Other Common: asthenic syndrome From the urinary system Patients treated with rosuvastatin may develop progeinuria. Changes in the amount of protein in the urine (from no or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10-20 mg of the drug, and in approximately 3% of patients receiving 40 mg of the drug. A slight change in the amount of protein in the urine was observed when taking a dose of 20 mg. In most cases, progeinuria decreases or disappears during therapy and does not indicate the occurrence of acute or progressive existing kidney disease. From the musculoskeletal system The following effects on the musculoskeletal system have been reported with rosuvastatin in all dosages and, in particular, with doses exceeding 20 mg: myalgia, myopathy (including myositis), in rare cases rhabdomyolysis with or without acute renal failure. A dose-dependent increase in creatine phosphokinase (CPK) activity was observed in a small number of patients taking rosuvastatin. In most cases, it was minor, asymptomatic, and temporary. In case of an increase in CPK activity (more than 5 times compared to the upper limit of normal), therapy should be suspended. 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, it is minor, asymptomatic, and temporary. Laboratory parameters Increased concentration of glucose, billirubin, activity of gamma-glutamyltranspeptidase, alkaline phosphatase, thyroid function disorders. Post-marketing application The following side effects have been reported in post-marketing use of rosuvastatin: :  From the hematopoietic system:  Rare: thrombocytopenia. From the digestive tract Very rare: jaundice, hepatitis Rare: increased activity of “hepatic” transaminases Frequency not established: diarrhea From the musculoskeletal system Very rare: arthralgia Frequency not established: immune-mediated necrotizing myopathy. From the central nervous system Very rare: polyneuropathy, memory loss From the respiratory system, the frequency is not established: cough, shortness of breath. From the urinary system Very rare: hematuria. From the side of the skin and subcutaneous fat, the frequency is not established: Stevens-Johnson syndrome On the part of the reproductive system, the frequency is not established: gynecomastia. Other Frequency not established: peripheral edema. The following side effects have been reported with some statins: depression, sleep disorders including insomnia and nightmarish dreams, and sexual dysfunction. Isolated cases of interstitial lung disease have been reported, especially with long-term drug use.

Interaction

Transport protein inhibitors

Rosuvastatin binds to some transport proteins, in particular, to OATP1 In 1 and BCRP. Concomitant use of drugs that are inhibitors of transport proteins may be accompanied by an increase in the concentration of rosuvastatin in blood plasma and an increased risk of developing myopathy.

Cyclosporine: When rosuvastatin and cyclosporine were co-administered, the AUC of rosuvastatin was on average 7 times higher than that observed in healthy volunteers. It does not affect the plasma concentration of cyclosporine. The drug Ro-statin is contraindicated in patients taking cyclosporine.

Indirect anticoagulants: initiation of rosuvastatin therapy or an increase in the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in prothrombin time (International Normalized Ratio – MHO). Discontinuation of rosuvastatin or a reduction in the dose of the drug may lead to a decrease in MHO.

Gemfibrozil and other lipid-lowering agents are recommended in such cases: the combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in the maximum concentration of rosuvastatin in blood plasma and the AUC of rosuvastatin. Based on the specific interaction data, no pharmacokinetically significant interaction with fenofibrate is expected, and a pharmacodynamic interaction is possible.

Gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses of nicotinic acid (greater than 1 g / day) increased the risk of myopathy when co-administered with HMG-CoA reductase inhibitors, possibly due to the fact that they can also cause myopathy when used in monotherapy.

When taking the drug simultaneously with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), patients are recommended an initial dose of 5 mg, taking a dose of 40 mg is contraindicated when administered simultaneously with fibrates.

Ezetimibe: concomitant use of 10 mg rosuvastatin and 10 mg ezetimibe was associated with an increase in rosuvastatin AUC in patients with hypercholesterolemia. An increased risk of side effects due to the pharmacodynamic interaction between Ro-statin and ezetimibe cannot be excluded.

HIV protease inhibitors (human immunodeficiency virus): Although the exact mechanism of interaction is unknown, co-use of HIV protease inhibitors can lead to a significant increase in rosuvastatin exposure.

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 and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 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 leads to a decrease in the AUC of rosuvastatin by 20% and the Cmax of rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by taking erythromycin.

Oral contraceptives/gyurmonosametive therapy: concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives.

Pharmacokinetic data on the concomitant use of the drug Ro-statin and hormone replacement therapy are not available, therefore, it is impossible to exclude a similar effect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients. Other medicinal products: no clinically significant interaction of rosuvastatin with digoxin is expected.

Cytochrome P450 isoenzymes: In vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes.

Therefore, rosuvastatin is not expected to interact with other drugs at the level of metabolism involving cytochrome P450 isoenzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 and CYP3A4 isoenzymes).

Drug interactions that require dose adjustment of rosuvastatin

The dose of Ro-statin should be adjusted if it is necessary to use it simultaneously with drugs that increase exposure to rosuvastatin. If exposure is expected to increase by a factor of 2 or more, the initial dose of Ro-statin should be 5 mg once a day.

It is also necessary to adjust the maximum daily dose of Ro-statin so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without simultaneous use of drugs that interact with rosuvastatin.

For example, the maximum daily dose of Ro-statin when used concomitantly with gemfibrozil is 20 mg (1.9-fold increase in exposure), with ritonavir/atazanavir-10 mg (3.1-fold increase in exposure).

How to take, course of use and dosage

Inside, do not chew or open the capsule, swallow whole with water. The drug can be prescribed at any time of the day, regardless of the time of eating. Before starting therapy with Ro-statin, the patient should begin to follow a standard hypocholesterolemic 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 current recommendations for the target concentration of lipids. 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 Ro-statin 1 time per day. When choosing the initial dose, you should be guided by the individual cholesterol concentration and take into account the possible risk of cardiovascular complications, as well as the potential risk of side effects. If necessary, the dose can be increased to a larger one after 4 weeks. Due to the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug, an increase in the dose to 40 mg, after an additional dose above the recommended initial dose 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 familial hypercholesterolemia), Especially 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 Ro-statin, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required). Elderly patients The initial recommended dose for patients over 70 years of age is 5 mg, otherwise no dose adjustment is required depending on age. Patients with renal insufficiency No dose adjustment is required in patients with mild or moderate renal insufficiency. The use of all dosages of Ro-statin is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min). It is contraindicated to use the drug in a dosage of 40 mg in patients with moderate renal impairment (creatinine clearance less than 60 ml / min). Patients with moderate renal impairment (creatinine clearance less than 60 ml / min) An initial dose of 5 mg is recommended. Patients with hepatic insufficiency Ro-statin 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 Japanese and Chinese was noted. This fact should be taken into account when prescribing Ro-statin to these groups of patients. When prescribing doses of 10 and 20 mg, the recommended starting dose for patients of the Mongolian race is 5 mg. It is contraindicated to prescribe the drug at a dose of 40 mg to patients of the Mongolian race. Patients predisposed to myopathycontradiction of the drug at a dose of 40 mg 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. Genetic polymorphism of carriers of genotypes SLC01B1 (OATR 1 In 1) c. 521CChABCG2 (BCRP) p. 421 AA showed an increase in exposure (AUC) to rosuvastatin compared with carriers of genotypes SLC01B1 p. 521 TT and ABCG2 p. 421 CC. For patients with C. 521 CC or C. 421 AA genotypes, the recommended maximum dose of Ro-statin is 20 mg once a day. Concomitant therapy Rosuvastatin binds to various transport proteins (in particular, OATP1 In 1 and BCRP). Concomitant use of Ro-statin with medications (such as cyclosporine, certain HIV protease inhibitors, including ritonavir/atazanavir, lopinavir, and / or tipranavir) that increase the plasma concentration of rosuvastatin due to interaction with transport proteins may increase the risk of myopathy (including rhabdomyolysis). In such cases, the possibility of prescribing alternative therapy or temporarily stopping the use of Ro-statin should be evaluated. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with Ro-statin should be evaluated and the possibility of reducing its dose should be considered.

Overdose

Symptoms: the pharmacokinetic parameters of rosuvastatin do not change with simultaneous use of several daily doses. Treatment: There is no specific treatment for rosuvastatin overdose. In case of overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. Monitoring of liver function and CKD levels is necessary. It is unlikely that hemodialysis will be effective.

Special instructions

From the urinary system

Patients receiving high doses of rosuvastatin (mainly 40 mg) experienced tubular proteinuria, which in most cases was transient. Such proteinuria did not indicate acute kidney disease or progression of kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor the indicators of renal function during treatment.

From the musculoskeletal system

When using rosuvastatin in all dosages and, in particular, when taking doses of the drug exceeding 20 mg, the following effects on the musculoskeletal system have been reported: myalgia, myopathy, and in rare cases rhabdomyolysis.

Determination of creatine phosphokinase activity

Determination of CKD activity should not be performed after intense physical exertion or in the presence of other possible causes of increased CKD activity, which may lead to misinterpretation of the results obtained. If the initial CPK activity is significantly increased (5 times higher than the upper limit of normal), a second measurement should be performed after 5-7 days.

You should not start therapy if a repeated test confirms the initial CPK activity (more than 5 times higher than the upper limit of normal).

Before starting therapy

When prescribing Ro-statin, as well as when prescribing other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy/rhabdomyolysis, it is necessary to consider the risk – benefit ratio of therapy and conduct clinical monitoring.

During therapy

The patient should 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 and fever. In such patients, CPK activity should be determined.

Therapy should be discontinued if CKD activity is significantly increased (more than 5 times higher than the upper limit of normal) or if muscle symptoms are severe and cause daily discomfort (even if CKD activity is 5 times lower than the upper limit of normal).

If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Po-statin or other HMG-CoA reductase inhibitors in lower doses, with careful monitoring of the patient. Routine monitoring of CPK activity in the absence of symptoms is impractical.

Very rare cases of immune-mediated necrotizing myopathy have been reported with clinical manifestations of persistent weakness of the proximal muscles and increased serum creatinine clearance during treatment or upon discontinuation of statins, including rosuvastatin.

Additional studies of the muscular system and nervous system, serological studies, and immunosuppressive therapy may be required.

There were no signs of increased effects on skeletal muscle when taking Ro-statin and concomitant therapy. However, an increase in myositis and myopathy has been reported in patients treated with other HMG-CoA reductase inhibitors in combination with fibrinic acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g/day), azole antifungal agents, HIV protease inhibitors, and macrolide antibiotics.

Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Therefore, the concomitant use of Ro-statin and gemfibrozil is not recommended. The risk-benefit ratio should be carefully weighed when using Ro-statin together with fibrates or lipid-lowering doses of nicotinic acid (more than 1 g/day).

It is contraindicated to take the drug Ro-statin in a dose of 40 mg together with fibrates. In 2-4 weeks after the start of treatment and/or with an increase in the dose of Ro-statin, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required).

Effects on liver function

It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. Taking the drug Ro-statin should be discontinued or the dose of the drug should be reduced if the activity of “hepatic” transaminases in the blood serum is 3 times higher than the upper limit of normal.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying diseases should be performed before starting treatment with Ro-statin.

Special populations.

Ethnic groups

In the course of pharmacokinetic studies among Chinese and Japanese patients, an increase in the systemic concentration of rosuvastatin was noted compared with the indicators obtained among European patients.

HIV protease inhibitors

Concomitant use of the drug with HIV protease inhibitors is not recommended.

Lactose

The drug should not be used in patients with lacgas insufficiency, 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, an unproductive cough, and poor overall health (weakness, weight loss, and fever).

If interstitial lung disease is suspected, statin therapy should be discontinued.

Type 2 diabetes mellitus

In patients with a glucose concentration of 5.6 to 6.9 mmol / L, rosuvastatin therapy was associated with an increased risk of developing type 2 diabetes. HMG-CoA reductase inhibitors, including Ro-statin, may increase blood glucose concentrations.

Influence on the ability to drive vehicles and other mechanisms

No studies have been conducted to study the effect of rosuvastatin on the ability to drive a vehicle and use mechanisms. Caution should be exercised when driving vehicles or working with increased concentration and psychomotor response (dizziness may occur during therapy).

Storage conditions

Store in a dark place at a temperature not exceeding 25° C. Keep out of the reach of children.

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Capsules