Rosuvastatin pills 10mg, 90pcs

Composition

Active ingredient:  rosuvastatin calcium-10.4 mg (in terms of rosuvastatin-10.0 mg); excipients:  lactose monohydrate-109.8 mg, microcrystalline cellulose-36.0 mg, calcium hydrophosphate dihydrate-13.0 mg, crospovidone-9.0 mg, magnesium stearate-1.8 mg; film coating: [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 mixture 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

Pharmacological action

Rosuvastatin is a selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, a cholesterol precursor. The main target of rosuvastatin action is the liver, where the synthesis of cholesterol (Ch) and catabolism of low-density lipoprotein cholesterol (LDL-C) is carried out. 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-C), thereby reducing the total amount of LDL-C and VLDL-C. Rosuvastatin reduces elevated concentrations of LDL-C, total cholesterol, and 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), VLDL-C, and TG, and increases the concentration of apolipoprotein A I (ApoA-I), reduces the ratio of cholesterol to cholesterol. LDL/HDL-C, total cholesterol/HDL-C and non-LDL/ HDL-C, and the apoB/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 use of the drug. Rosuvastatin is effective in adult patients with hypercholesterolemia, with or without hypertriglyceridemia, including those with diabetes mellitus and familial hypercholesterolemia. The additive effect is observed in combination with fenofibrate (in relation to the concentration of TG) and nicotinic acid in lipid-lowering doses (in relation to the concentration of HDL-C), but the possibility of such combinations should be evaluated by the attending physician, taking into account possible risks.

Indications

– Primary hypercholesterolemia according to the classification of Fredrickson (type IIA including heterozygous family hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other non-pharmacological treatments (e. g. exercise, weight reduction) are insufficient; family homozygous hypercholesterolemia as an adjunct to diet and other lepidosauria therapy (e. g. LDL-apheresis), or in cases where such treatment is not effective enough, hypertriglyceridemia (type IV according to the classification of 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; – primary prevention of major cardiovascular complications (stroke, myocardial infarction, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), 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 (more than 2 mg/l) in the presence of at least one additional risk factors, such as hypertension, low concentration of HDL-C, Smoking, family history of early CHD).

Use during pregnancy and lactation

Rosuvastatin is contraindicated during pregnancy and lactation. Women of reproductive age should use adequate methods of contraception. Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of HMG-CoA reductase inhibition for the fetus exceeds the benefit of using rosuvastatin during pregnancy. In case of pregnancy during therapy, the use of the drug should be stopped 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), so the use of the drug should be discontinued during breast-feeding. Category of action on the fetus according to the FDA-X.

Recommendations for use

Inside, do not chew or crush the tablet, 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 Rosuvastatin, 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 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 the initial dose, you should be guided by the individual cholesterol content 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 (see section “Side effects”), 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 Rosuvastatin, monitoring of lipid metabolism parameters is necessary (if necessary, 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 Do not require dose adjustment. Patients with renal insufficiency : No dose adjustment is required in patients with mild or moderate renal insufficiency. In patients with severe renal insufficiency (creatinine clearance less than 30 ml/min), the use of Rosuvastatin is contraindicated. It is contraindicated to use the drug at a dose of 40 mg in patients with moderate renal impairment (creatinine clearance 30-60 ml / min). In patients with moderate renal impairment, an initial dose of 5 mg is recommended. Patients with hepatic insufficiency: Rosuvastatin is contraindicated in patients with active liver disease in the general population. 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 (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 Mongolian race is 5 mg. It is contraindicated to prescribe the drug at a dose of 40 mg to patients of the Mongolian race (see the section “Contraindications”). Genetic polymorphism In carriers of genotypes SLCO1B1 (OATP1B1) c. 521CC and ABCG2 (BCRP) c. 421%%AA The recommended maximum dose of Rosuvastatin is 20 mg once a day. Patients predisposed to myopathy It is contraindicated to prescribe the drug at a dose of 40 mg to 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, to OATP%%B%^%1 and BCRP). Co-administration of Rosuvastatin with medicinal products (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 alternative therapy or temporary discontinuation of Rosuvastatin should be evaluated. If the use of the above drugs is necessary, the benefit-risk ratio 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 diseases in the active phase (including a persistent increase in the activity of hepatic transaminases and an increase in the activity of hepatic transaminases in blood serum by more than 3 times compared to ULN); severe renal insufficiency (creatinine clearance. Daily dose of 30 mg or more: hypersensitivity to rosuvastatin; liver diseases in the active phase (including a persistent increase in the activity of hepatic transaminases and an increase in the activity of hepatic transaminases in blood serum by more than 3 times compared to ULN); moderate to severe renal insufficiency (creatinine clearance)

Side effects

Side effects observed with the use of rosuvastatin are usually mild and go away on their own. As with other HMG-CoA reductase inhibitors, the frequency of side effects is mainly dose-dependent. WHO classification of the frequency of side effects: very common (≥1/10); common (≥1/100, From the blood and lymphatic system: frequency unknown-thrombocytopenia. Immune system disorders: 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 loss of memory; frequency unknown-peripheral neuropathy. Respiratory, thoracic and mediastinal disorders: frequency 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 blood plasma is observed in a small number of patients. In most cases, it is minor, asymptomatic, and temporary. From the skin and subcutaneous tissues: infrequently-pruritus, skin rash, urticaria; frequency unknown-Stevens-Johnson syndrome. Musculoskeletal and connective tissue disorders: common-myalgia; rare-myopathy (including myositis), rhabdomyolysis (with or without acute renal failure); very rare — arthralgia; frequency unknown — immune-mediated necrotizing myopathy. A dose-dependent increase in CPK activity in blood plasma is observed in a small number of patients taking rosuvastatin. In most cases, it is minor, asymptomatic, and temporary. If the activity of CPK in blood plasma is more than 5 times higher than the ULN, therapy should be suspended. From the side of the kidneys and urinary tract: proteinuria may occur in patients receiving rosuvastatin therapy. 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 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 observed when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or progressive existing kidney disease; very rarely, hematuria. Genital and breast disorders: frequency unknown-gynecomastia. General disorders and disorders at the injection site: often-asthenic syndrome; frequency unknown-peripheral edema. Laboratory parameters: hyperglycemia, increased bilirubin concentration in blood plasma, GGTP activity, ALP in blood plasma, changes in the serum concentration of thyroid hormones. The following side effects have been reported with some HMG-CoA reductase inhibitors (statins): depression, sleep disorders, including insomnia and nightmares, sexual dysfunction, and increased glycosylated hemoglobin concentrations. Isolated cases of interstitial lung disease have been reported, especially with prolonged use of these agents

Interaction

Inhibitors of transport proteins: rosuvastatin binds to some transport proteins, in particular, to OATP1 In 1 and BCRP. Concomitant use of drugs that are inhibitors of these 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. 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-use of HIV protease inhibitors and rosuvastatin may result in a significant increase in rosuvastatin AUC. A pharmacokinetic study on the concomitant use of 20 mg rosuvastatin with a combination drug containing two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in an increase in the AUC(0-24) and Cmax of rosuvastatin by approximately 2 and 5 times, respectively. Therefore, simultaneous 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 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 cause myopathy and when used as monotherapy (see section “Special instructions”). When taking Rosuvastatin concomitantly 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 co-administered 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 (see table). An increased risk of side effects due to the pharmacodynamic interaction between Rosuvastatin and ezetimibe cannot be excluded. 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 resulted in a 20% decrease in rosuvastatin AUC and a 30% decrease in rosuvastatin cmax. This interaction may occur as a result of increased intestinal motility caused by taking erythromycin. 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 of rosuvastatin with fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the 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 rhabdomyolysis with co-use of rosuvastatin and fusidic acid. Patients should be carefully monitored. If necessary, it is possible to temporarily stop taking the drug Rosuvastatin.

Overdose

Symptoms: the clinical picture of overdose is not described. The pharmacokinetic parameters of rosuvastatin do not change with simultaneous use of several daily doses. Treatment: symptomatic, monitoring of liver function and CKD activity is necessary; there is no specific antidote, and hemodialysis is ineffective.

Special instructions

Impaired renal function. In patients receiving high doses of rosuvastatin (in particular,40 mg/day), tubular proteinuria was observed, which was detected using test strips and in most cases was periodic or short-term. Such proteinuria does not indicate an acute disease or progression of concomitant kidney disease. The incidence of serious renal impairment observed in the post-marketing study 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 the indicators of renal function during treatment (at least once every 3 months). Influence on the musculoskeletal system. The following effects on the musculoskeletal system have been reported with rosuvastatin at all doses, but especially at doses exceeding 20 mg / day: myalgia, myopathy, and in rare cases rhabdomyolysis. Very rare cases of rhabdomyolysis have been reported with concomitant use of HMG-CoA reductase inhibitors and ezetimibe. This combination should be used with caution, as a pharmacodynamic interaction cannot be excluded.As with other HMG-CoA reductase inhibitors, the incidence of rhabdomyolysis with post-marketing use of rosuvastatin is higher with a dose of 40 mg / day Determination of CKD activity. CPK activity cannot be determined after intense physical exertion and in the presence of other possible reasons for its increased activity; this may lead to incorrect interpretation of the results obtained. If the initial CPK activity is significantly exceeded (5 times higher than ULN), a second analysis should be performed after 5-7 days. You should not start therapy if the results of repeated analysis confirm the initial high activity of CKK (more than 5 times the 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); myotoxic events when taking other HMG-CoA reductase inhibitors or fibrates in the anamnesis; excessive alcohol consumption; age over 65 years; 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 benefit of therapy. Clinical monitoring is also recommended. If the initial CPK activity is more than 5 times higher than the ULN, rosuvastatin therapy should not be initiated. During rosuvastatin therapy, the patient should be informed about the need for immediate medical attention in case of unexpected occurrence of 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 the ULN) or muscle symptoms are severe and cause daily discomfort (even if CKD activity is not more than 5 times 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 careful medical supervision. Monitoring CPK activity in the absence of symptoms is impractical. Very rare cases of immuno-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 were noted during therapy or upon discontinuation of HMG-CoA reductase inhibitors, including rosuvastatin. Additional studies of the muscular and nervous system, 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 treated with other HMG-CoA reductase inhibitors in combination with fibroic acid derivatives (e. g. gemfibrozil), cyclosporine, nicotinic acid in lipid — lowering doses (more than 1 g/day), antifungal agents such as azole derivatives, HIV protease inhibitors, and macrolide antibiotics. When used concomitantly with certain HMG-CoA reductase inhibitors, gemfibrozil increases the risk of developing myopathy. Therefore, the concomitant use of rosuvastatin and gemfibrozil is not recommended. The benefits of further changes in plasma lipid concentrations when combined with fibrates or nicotinic acid in lipid-lowering doses should be carefully weighed against the possible risk. Rosuvastatin 30 mg / day is contraindicated in combination therapy with fibrates. Due to the increased risk of rhabdomyolysis, rosuvastatin should not be used in patients with acute conditions that may lead to myopathy, or conditions predisposing to the development of renal failure (for example, sepsis, hypotension, extensive surgery, trauma, severe metabolic, endocrine and electrolyte disorders, 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 a history of liver disease (see “Contraindications”, “Restrictions on use”). It is recommended to determine liver function tests before the start of therapy and 3 months after its start. The use of rosuvastatin should be discontinued or the dose of this drug 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, treatment of the underlying diseases should be performed before starting treatment with rosuvastatin. Ethnic features. In the course of pharmacokinetic studies, an increase in the plasma concentration of rosuvastatin was observed in representatives of the Mongolian race compared with representatives of the Caucasian race. Interstitial lung disease. Isolated cases of interstitial lung disease have been reported with the use of certain HMG-CoA reductase inhibitors, 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, HMG-CoA reductase inhibitors 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 mellitus. Effects on the ability to drive a car or perform work requiring increased speed of physical and mental reactions. Studies on the effect of rosuvastatin on the ability to drive vehicles and work with mechanisms have not been conducted. However, given the possibility of dizziness and other side effects, caution should be exercised 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 reach of children.

Shelf life

2 years

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets