rosuvastatin | Rosucard tablets are covered.pl.ob. 20 mg, 60 pcs.

Pharmacological action

Hypolipidemic agent from the group of statins. Selective competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase-enzyme, converting HMG-CoA to mevalonate, a precursor of cholesterol (cholesterol).

Increases the number of low density lipoprotein receptors (LDL) on the surface of hepatocytes, which leads to increased uptake and catabolism of LDL, inhibition of very low density lipoprotein synthesis (VLDL), reducing the total concentration of LDL and VLDL. Reduces the concentration of LDL cholesterol, high-density non-lipiprotein cholesterol (non-HDL cholesterol), cholesterol-VLDL, total cholesterol, triglycerides (TG), TG-VLDL, apolipoprotein B (ApoV), reduces the ratio of LDL-C / LDL cholesterol Cholesterol-cholesterol-HDL, cholesterol-HDL / cholesterol-HDL, ApoV / apolipoprotein A-1 (ApoA-I), increases the concentration of HDL-cholesterol and ApoA-I.

Hypolipidemic effect is directly proportional to the size of the prescribed dose. The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks reaches 90% of the maximum, by 4 weeks reaches a maximum and after that remains constant. Effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender or age), including patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with type IIa and IIb hypercholesterolemia (Fredrickson classification) with an average initial concentration of LDL-C about 4.8 mmol / L while taking the drug at a dose of 10 mg, the concentration of LDL-C reaches less than 3 mmol / L. In patients with homozygous familial hypercholesterolemia, taking the drug at a dose of 20 mg and 40 mg, the average decrease in the concentration of LDL-C is 22%.

An additive effect is observed in combination with fenofibrate (in relation to a decrease in the concentration of TG and with nicotinic acid in lipid lowering doses (not less than 1 g / day) (in relation to a decrease in the concentration of HDL-C).

Pharmacokinetics

Absorption

Maximum concentration cstax in blood plasma is reached approximately 5 hours after taking the drug.The absolute bioavailability is approximately 20%. The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily m admission

Distribution

Penetrates through the placental barrier. Rosuvastatin is absorbed primarily by the liver, which is the main site of cholesterol synthesis and metabolism of LDL-C. Distribution volume - 134 l. Binding to plasma proteins (mainly with albumin) is approximately 90%.

Metabolism

Biotransformed in the liver to a small degree (about 10%), being a non-core substrate for isoenzymes of the cytochrome P450 system. As in the case of other HMG-CoA reductase inhibitors, a specific membrane carrier is involved in the process of hepatic uptake of the drug - a polypeptide transporting the organic anion (OATP) 1B1, which plays an important role in its hepatic elimination. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. Isoenzymes CYP2C19, CYP3A4, and CYP2D6 are less involved in metabolism.

The main metabolites of rosuvastatin are N-dismethyl and lactone metabolites. N-dismethyl is about 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is metabolites.

Excretion

About 90% of the dose of rosuvastatin is excreted unchanged through the intestines, the remainder by the kidneys. The half-life (T1 / 2) is approximately 19 hours, does not change with an increase in the dose of the drug. The average plasma clearance is approximately 50 l / h (coefficient of variation 21.7%).

In patients with mild to moderate renal failure, the plasma concentration of rosuvastatin or N-dysmethyl does not change significantly. In patients with severe renal failure (creatinine clearance (CC) less than 30 ml / min), the concentration of rosuvastatin in blood plasma is 3 times higher, and N-dismethyl - 9 times, than healthy volunteers. The concentration of rosuvastatin in plasma in patients on hemodialysis is approximately 50% higher than in healthy volunteers.

Patients with a score of 7 or lower on the Child-Pugh scale did not show an increase in T1 / 2 of rosuvastatin in patients with a score of 8 and 9 on the Child-Pugh scale, a 2-fold elongation of T1 / 2 was noted. There is no experience with the use of the drug in patients with more severe impaired liver function.

Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.

Ethnic groups

The pharmacokinetic parameters of rosuvastatin depend on race: the area under the concentration-time (AUC) curve of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese, and Koreans) is 2 times higher than that of the Caucasian race. In Indians, the average value of AUC and C max increased by 1.3 times.

Indications

Primary hypercholesterolemia (type IIa according to Fredrickson), including heterozygous hereditary hypercholesterolemia or mixed (combined) hypercholesterolemia (type IIb according to Fredrickson), as an addition to diet and other non-drug measures (physical activity and weight loss) with the ineffectiveness of diet therapy and non-drug measures

Homozygous form of hereditary hypercholesterolemia and with insufficient effectiveness of diet therapy and other types of treatment aimed at lowering lipids (for example, LDL apheresis), or if such treatments are not suitable for the patient.

Hypertriglyceridemia (type IV Fredrickson supplementation) as a diet supplement.

To slow the progression of atherosclerosis as a supplement to the diet in patients who are shown therapy to reduce the concentration of total cholesterol and cholesterol - LDL.

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 older than 50 years for men and older than 60 years for women, increased concentration of C-reactive protein ( 2 mg / l) with the presence of at least one of the additional risk factors, such as arterial hypertension, low concentration of HDL-C, smoking, a family history of early onset of coronary heart disease).

Contraindications

Hypersensitivity to rosuvastatin or other components of the

preparation Liver diseases in the active phase or a steady increase in serum activity of “liver” transaminases (more than 3 times compared with the upper limit of norm) of unclear origin, liver failure (severity from 7 up to 9 points on the Child-Pugh scale)

An increase in the concentration of creatinine phosphokinase (CPK) in the blood by more than 5 times compared with the upper limit of normal (VGN)

Inherited diseases such as to lactose intolerance, lactase deficiency or glucose-galactose malabsorption (due to the presence of lactose)

Expressed renal dysfunction (creatinine clearance less than 30 mL / min)

Myopathy

Patients predisposed to the development of myotoxic complications

Simultaneous use of cyclosporine

Joint use with HIV protease inhibitors

Women of reproductive age who do not use adequate methods of contraception

Pregnancy and lactation

Age up to 18 years (efficacy and safety have not been established).

Use during pregnancy and lactation

The use of Rosucard in women of reproductive age is possible only if reliable contraception methods are used and if the patient is informed about the possible risk of treatment for the fetus.

Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefits of using the drug during pregnancy. Rosucard is contraindicated in pregnancy and lactation. If pregnancy is diagnosed during the course of drug therapy, Rosucard should be stopped immediately, and the patient should be warned of the potential risk to the fetus.

If necessary, use the drug during lactation, given the possibility of adverse events in infants, the question of stopping breastfeeding should be decided.

Special instructions

During treatment, especially during the dose adjustment period of the drug RosucardВ®, every 2-4 weeks should monitor the lipid profile and, if necessary, change the dose of the drug.

It is recommended that liver function tests be determined prior to initiation of therapy and 3 months after initiation of therapy. The use of the drug RosucardВ® should be discontinued or the dose of the drug should be reduced if the level of activity of hepatic transaminases in the blood serum is 3 times higher than VGN.

When using RosucardВ® at a dose of 40 mg, it is recommended to monitor renal function.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of underlying diseases should be carried out before treatment with RosucardВ®.

In patients with existing risk factors for rhabdomyolysis, it is necessary to consider the ratio of expected benefits and potential risks and conduct clinical observation throughout the course of treatment.

Inform patient that immediate medical attention should be given to cases of muscle pain, muscle weakness, or cramping, especially in combination with malaise and fever.

In such patients, CPK activity should be determined. Therapy should be discontinued if the activity of CPK is significantly increased (more than 5 times compared with VGN) or muscle symptoms are pronounced and cause daily discomfort. If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing RosucardВ® or other HMG-CoA reductase inhibitors in lower doses with careful monitoring of the patient.

Determination of CPK activity should not be carried out after intense physical exertion or if there are other possible reasons for its increase, which may lead to an incorrect interpretation of the results. If the initial activity of CPK is significantly increased, after 5-7 days, a second measurement should be carried out - you can not start therapy if a second test confirms the initial activity of CPK (5 times higher than normal).

Routine monitoring of CPK activity in the absence of the above symptoms is impractical.

An increase in the incidence of myositis and myopathy in patients taking other HMG-CoA reductase inhibitors in combination with fibrates (including gemfibrozil), cyclosporine, nicotinic acid, azole antifungal drugs, protease inhibitors and macrolide antibiotics. The ratio of the expected benefit and potential risk should be carefully weighed when the rosucardВ® drug is combined with fibrates or nicotinic acid (in lipid-lowering doses - 1 g / day), the simultaneous administration of gemfibrozil is not recommended.

In most cases, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or exacerbation of an existing kidney disease. Assessment of renal function should be performed during routine examination of patients receiving a dose of 40 mg.

Statin drugs can cause an increase in blood glucose. In some patients at high risk of developing diabetes, such changes can lead to its manifestation, which is an indication for the appointment of hypoglycemic therapy. However, the decrease in the risk of vascular diseases with statins increases the risk of developing diabetes mellitus, therefore, this factor should not serve as a basis for canceling statin treatment. Patients at risk (fasting blood glucose concentration of 5.6–6.9 mmol / L, BMI> 30 kg / m2, history of hypertriglyceridemia, history of arterial hypertension) should be monitored and biochemical parameters monitored regularly.

Co-administration of rosuvastatin and HIV protease inhibitors is not recommended.

With prolonged use of rosuvastatin, isolated cases of interstitial lung disease have been reported. If you suspect an interstitial lung disease, you must stop therapy with RosucardВ®.

When studying the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was observed in representatives of the Mongoloid race (see "Pharmacokinetics"). This fact should be taken into account when prescribing RosucardВ® to these patients.

Influence on the ability to drive vehicles and work with mechanisms. Caution should be exercised when driving vehicles and activities that require an increased concentration of attention and speed of psychomotor reactions (dizziness may occur during therapy).

Composition

Each 20 mg film-coated tablet contains: Active ingredient: rosuvastatin - 20,000 mg (in the form of calcium rosuvastatin - 20,800 mg)

Excipients: core: lactose monohydrate - 120,000 mg, microcrystalline cellulose - 90.8 - 90.8 mg 2,400 mg, colloidal silicon dioxide - 1,200 mg, magnesium stearate - 4,800 mg

film coating: hypromellose 2910/5 - 5,000 mg, macrogol 6000 - 0,800 mg, titanium dioxide - 0,650 mg, talc - 0,950 mg, iron dye red oxide - 0 , 065 mg.

Dosage and Administration

Inside, without chewing or grinding, swallow whole, washed down with water, at any time of the day, regardless of food intake.

Before starting therapy with Rosucard, the patient should begin to follow a standard lipid-lowering diet and continue to follow it during treatment. The dose of the drug should be selected individually depending on the indications and therapeutic response, taking into account current generally accepted recommendations for target lipid levels. If it is necessary to take the drug in a dose of 5 mg, a 10 mg tablet should be divided into two parts at risk.

The recommended starting dose of Rosucard for patients starting to take the drug, or for patients transferred from other HMG-CoA reductase inhibitors, is 5 or 10 mg once daily. When choosing an initial dose, one should be guided by the patient’s cholesterol content and take into account the risk of developing cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, after 4 weeks the dose of the drug can be increased.

Due to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug (see section “Side effects”), final titration to a maximum dose of 40 mg should be performed only in patients with severe hypercholesterolemia and a high risk of cardiovascular vascular complications (especially in patients with hereditary hypercholesterolemia), in which, at a dose of 20 mg, the target cholesterol level was not achieved, and which will be under medical supervision.

Patients with hepatic insufficiency

In patients with hepatic insufficiency with values ​​on the Child-Pugh scale below 7 Rosucard dose adjustment points are not required.

Patients with renal failure

Dose adjustment is not required in patients with mild renal failure. The recommended initial dose of Rosucard is 5 mg per day.

In patients with severe renal failure (CC less than 30 ml / min), the use of Rosucard is contraindicated.

In patients with moderate renal insufficiency (CC 30 - 60 ml / min), the use of Rosucard at a dose of 40 mg per day is contraindicated (see section "Contraindications").

Special Populations. Elderly

patients Dose adjustment is not required in patients over 65 years of age.

Patients with a predisposition to myopathy

The use of rosucard at a dose of 40 mg per day is contraindicated in patients with a predisposition to myopathy (see section "Contraindications"). When prescribing doses of 10 mg and 20 mg per day, the recommended initial dose of Rosucard for this group of patients is 5 mg per day.

Ethnic groups

When studying the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was observed in representatives of the Mongoloid race (see the section “Pharmacokinetics”). This fact should be taken into account when prescribing Rosucard to patients of the Mongoloid race. When prescribing doses of 10 and 20 mg, the recommended initial dose of Rosucard for this group of patients is 5 mg per day. The use of Rosucard at a dose of 40 mg per day in representatives of the Mongoloid race is contraindicated (see section "Contraindications).

When prescribing Rosucard with gemfibrozil, the dose should not exceed 10 mg per day.

Side effects

The frequency of adverse reactions was determined according to the following gradation (World Health Organization classification):

very often - more than 1/10,

often - more than 1/100 to less than 1/10,

infrequently - more than 1/1000 to less than 1/100,

rarely - from more than 1/10000 to less than 1/1000,

very rarely - from less than 1/10000, including individual messages.

unspecified frequency.

From the central nervous system: often - headache, dizziness, asthenic syndrome is very rare - peripheral neuropathy, memory impairment.

From the digestive system: often - nausea, constipation, abdominal pain is rare - vomiting is rare - pancreatitis is very rare - hepatitis, jaundice of unspecified frequency - diarrhea.

From the respiratory system: infrequently - cough, dyspnea.

From the endocrine system: often - type 2 diabetes.

From the musculoskeletal system: often - myalgia is very rare - arthralgia is rare - myopathy (including myositis), rhabdomyolysis.

Allergic reactions: infrequently - skin itching, urticaria, rash rarely - angioedema.

Skin and subcutaneous tissue: unspecified frequency - Stevens-Johnson syndrome, peripheral edema.

From the urinary system: often - proteinuria (with a frequency of more than 3% in patients receiving a dose of 40 mg), decreasing during therapy and not related to the occurrence of kidney disease, urinary tract infection is very rare - hematuria.

Laboratory indicators: infrequently - a transient dose-dependent increase in serum creatine phosphokinase (CPK) activity, with an increase of more than 5 times compared with the upper limit of normal therapy should be temporarily suspended rarely - a transient increase in the activity of aspartate aminotransferase and alanine aminotransferase.

As with other HMG-CoA reductase inhibitors, the incidence is dose-dependent, side effects are usually mild and go away on their own.

When using ROSUKARDAά changes in the following laboratory parameters were noted: an increase in the concentration of glucose, bilirubin, alkaline phosphatase activity, gamma-glutamyl transferase.

When using other statins, the following side effects have been reported: depression, insomnia, decreased potency.

With prolonged use of rosuvastatin, isolated cases of interstitial lung disease have been reported.

Overdose of

With the simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.

Treatment: there is no specific treatment, symptomatic therapy is carried out to maintain the functions of vital organs and systems. It is necessary to monitor indicators of liver function and CPK activity. Hemodialysis is ineffective.

Storage conditions

At a temperature not exceeding 25 oС in the original packaging.

Expiration

2 years.

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rosuvastatin

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tablets