Instruction for use: Rosuvastatin 10mg

International Nonproprietary Name (INN): Rosuvastatin

Pharmaceutic group: lipid-lowering agents

Presentation:

Film-coated tablets of 5 mg, 10 mg and 20 mg. 10 tablets in packings Valium planimetric. 3 or 6 packages Valium planimetric along with instructions for use are placed in a pile of cardboard.

Indications for Rosuvastatin

Rosuvastatin - a drug prescribed by a doctor, therapist, cardiologist or other expert if the patient has certain cardiovascular problems and situations related to high cholesterol levels, or low or very low density lipoprotein.

Rosuvastatin is a hypolipidemic drug, a selective competitive inhibitor of the enzyme HMG CoA reductase which converts 3-hydroxy-3-metilglutarilKoA to mevalonate, a precursor of cholesterol (LDL). The primary target of action of rosuvastatin is the liver where it is carried out the synthesis and catabolism of cholesterol low density lipoprotein (LDL). Rosuvastatin reduces elevated concentrations of LDL-cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), increases the concentration of high-density lipoprotein-cholesterol (HDL-C). As a result of rosuvastatin observed reduction coefficient (index) atherogenic that characterizes the improvement of the lipid profile in patients with hypercholesterolemia.

= atherogenic index (total cholesterol - LDL-HDL) / HDL-C.

The therapeutic effect is within one week after initiation of treatment with rosuvastatin. Maximum therapeutic effect is usually achieved by the fourth week of therapy and is maintained at a regular intake of the drug.

Effective in adult patients with hypercholesterolemia, hypertriglyceridemia with or without, including patients with diabetes and familial hypercholesterolemia.

Our company already produces drugs from the statins, such as simvastatin and atorvastatin. It should be noted that all of these drugs, though combined in pharmacological action from the chemical point of view they are very diverse and little in common with one another in terms of chemical structure.

Rosuvastatin is taken once a day, a long course of treatment. One feature of this drug is its pharmacokinetic characteristics in patients Mongoloid race (Japanese, Chinese, Filipino, Vietnamese and Koreans) compared with Caucasians. It should be considered when selecting the dosage. Also, when selecting the dose should be considered function of the liver and kidneys.

Rosuvastatin belongs to a new generation of statins with good tolerability, low toxicity and high safety in case of overdose. Not recommended the appointment of a dose of 40 mg and higher in patients not previously go to the doctor.

Trade name of the drug – Rosuvastatin

Dosage Form: tablets

A film-coated tablet 5 mg comprises:

Active ingredient: calcium rosuvastatin - 5.21 mg (equivalent to 5.00 mg of rosuvastatin);

Excipients: Microcrystalline cellulose - 49.19 mg pregelatinized starch - 24,00 mg colloidal silicon dioxide (Aerosil) - 0.80 mg magnesium stearate - 0.80 mg;

shell Tablets: Opadry Pink 3.20 mg (lactose monohydrate - 1.28 mg hypromellose - 0.90 mg titanium dioxide - 0.75 mg Triacetin - 0.25 mg carmine red dye - 0.02 mg).

A film-coated tablet 10 mg contains:

Active ingredient: calcium rosuvastatin - 10.42 mg (calculated as rosuvastatin 10.00 mg);

Excipients: Microcrystalline cellulose - 98.38 mg pregelatinized starch - 48,00 mg colloidal silicon dioxide (Aerosil) - 1.60 mg magnesium stearate - 1.60 mg;

coated tablets: Opadry Pink 6.40 mg (lactose monohydrate - 2.56 mg, Valium - 1.80 mg titanium dioxide - 1.50 mg triacetin - 0.50 mg coloring agent carmine red - 0.04 mg).

A film-coated tablet 20 mg contains:

Active ingredient: calcium rosuvastatin - 20.84 mg (calculated as rosuvastatin 20.00 mg);

Excipients: microcrystalline cellulose - 196.76 mg, pregelatinised starch - 96.00 mg colloidal silicon dioxide (Aerosil) - 3.20 mg of magnesium stearate - 3,20 mg;

coated tablets: Opadry Pink 12.80 mg (lactose monohydrate - 5.12 mg, Valium - 3.60 mg of titanium dioxide - 3.00 mg triacetin - 1.00 mg coloring agent carmine red - 0.08 mg).

Description:

Round biconvex tablets, film-coated from light pink to pink. On cross-section - the inner layer of white or nearly white.

Pharmacotherapeutic group: lipid-lowering agents

ATX code: Ñ10ÀÀ07

Pharmacological Properties of Rosuvastatin

Pharmacodynamics

Lipid-lowering drugs, a selective competitive inhibitor of the enzyme HMG-CoA reductase that converts 3-hydroxy-3-metilglutarilKoA to mevalonate, a precursor of cholesterol (LDL). The primary target of action of rosuvastatin is the liver where it is carried out the synthesis and catabolism of cholesterol low density lipoprotein (LDL). Rosuvastatin increases the number of LDL receptors on the surface of liver cells, increasing the catabolism of LDL and a seizure, which in turn leads to inhibition of the synthesis of very low density lipoproteins (VLDL), thereby reducing the total amount of VLDL and LDL.

Rosuvastatin reduces elevated concentrations of LDL cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), increases the concentration of high-density-lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (apoB), LDL-VLDL , VLDL-TG and increases the concentration of apolipoprotein A-I (ApoA-I). As a result of rosuvastatin observed reduction coefficient (index) atherogenic that characterizes the improvement of the lipid profile in patients with hypercholesterolemia.

= atherogenic index (total cholesterol - LDL-HDL) / HDL-C.

The therapeutic effect is within one week after initiation of treatment with rosuvastatin. Maximum therapeutic effect is usually achieved by the fourth week of therapy and is maintained at a regular intake of the drug.

Effective in adult patients with hypercholesterolemia, hypertriglyceridemia with or without, including patients with diabetes and familial hypercholesterolemia.

An additive effect was observed in combination with fenofibrate (in respect of concentrations of TG) and nicotinic acid in the lipid-lowering doses (in relation to the concentration of HDL-C), but the very possibility of such combinations should be decided by the attending physician taking into account the potential risks (see. Also section "Special instructions ").

Pharmacokinetics

Absorption and distribution

Maximum concentration in plasma rosuvastatin (Cmax) is reached after approximately 5 hours after ingestion. The absolute bioavailability is approximately 20%.

Rosuvastatin is metabolized primarily by the liver, which is the main site of cholesterol synthesis and LDL-C metabolism. The volume of distribution of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin is bound to plasma proteins, mainly albumin.

Metabolism

Treated limited metabolism (approximately 10%). Rosuvastatin is a non-core substrate for the metabolism of cytochrome P450 isoenzymes system. The main isoenzyme involved in the metabolism of rosuvastatin is isoenzyme CYP2C9. Isozymes CYP2C19, CYP2D6 and CYP3A4 in the metabolism are involved to a lesser extent.

The main metabolites identified are the N-rosuvastatin desmetilrozuvastatin and lactone metabolites. N-desmetilrozuvastatin approximately 50% less active than the original rosuvastatin lactone metabolites are pharmacologically inactive. Over 90% of the pharmacological activity inhibiting circulating HMG-CoA reductase inhibitor rosuvastatin is provided, the rest - its metabolites.

breeding

About 90% of the dose of rosuvastatin is excreted unchanged through the intestines (including unabsorbed and absorbed rosuvastatin). The rest of the excreted by the kidneys. The plasma elimination half-life (T?) Is approximately 19 hours. The half-life does not change with increasing dose. The geometric mean plasma clearance of approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase, a process of "hepatic" capture membrane transporter involved rosuvastatin cholesterol performs important role in hepatic elimination of rosuvastatin.

Linearity

Systemic exposure of rosuvastatin increases in proportion to dose. Pharmacokinetic parameters did not change when taken daily.

Specific patient populations.

Age and sex

Gender and age did not have a clinically meaningful effect on the pharmacokinetics of rosuvastatin.

Ethnic groups

Pharmacokinetic studies have shown approximately a two-fold increase in AUC median (area under "concentration-time" curve) and the Cmax (maximum plasma concentration) of rosuvastatin in patients Mongoloid race (Japanese, Chinese, Filipino, Vietnamese and Koreans) compared with Caucasians; Indian patients have shown an increase in AUC and Cmax median 1.3 times. Pharmacokinetic analysis revealed no clinically relevant differences in the pharmacokinetics of rosuvastatin among Caucasians and blacks.

kidney failure

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

Liver failure

In patients with different stages of liver failure is not revealed an increase in half-life of rosuvastatin in patients with 7 points or less on the scale of Child-Pugh. In two patients with the 8-th and 9-th points on the Child-Pugh an increase in half-life at least 2 times. Experience in the use of rosuvastatin in patients with more than 9 th scores on the Child-Pugh is absent.

Genetic polymorphism

HMG-CoA reductase inhibitors, including Rosuvastatin, transport proteins bind OATR1V1 (organic anion transport polypeptide involved in the capture of statins hepatocytes) and BCRP (efflux transporter). Carriers genotypes SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA marked increase exposure (AUC) to rosuvastatin in 1.6 and 2.4 times, respectively, compared with native genotypes SLCO1B1 c.521TT and ABCG2 c .421CC.

Indications for Rosuvastatin

Primary Hypercholesterolemia Fredrickson classification (type IIa of, including heterozygous familial hypercholesterolaemia) or mixed hypercholesterolaemia (type IIb) as an adjunct to diet when diet and other non-pharmacological treatments (eg exercise, weight loss) are insufficient;

· Homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (eg, LDL-apheresis), or when such treatment is not effective enough;

· Hypertriglyceridemia (type IV classification Fredrickson) as an adjunct to diet;

· To slow the progression of atherosclerosis as an adjunct to diet in patients undergoing therapy shown to reduce concentrations of total cholesterol and LDL-C;

· Primary prevention of major cardiovascular events (stroke, heart attack, arterial revascularization) in adult patients without clinical evidence of coronary heart disease but with an increased risk of its development (age over 50 years for men and over 60 for women), increased concentration of C-reactive protein (≥ 2 mg / l) in the presence of at least one additional risk factors such as hypertension, low concentrations of HDL-C, smoking, family history of early onset coronary artery disease.

Contraindications for Rosuvastatin

For preparation at a daily dose of 5 mg, 10 mg and 20 mg:

• Hypersensitivity to rosuvastatin or any of the components;
• Lactose intolerance, lactase deficiency or glucose-galactose malabsorption (product contains lactose);
• Children up to age 18;
• Liver disease in its active phase, including persistent elevation of serum transaminases and any increase in transaminase activity in serum (more than 3 times the upper limit of normal);
• Severe renal dysfunction (creatinine clearance less than 30 mL / min);
• Myopathy and predisposition to develop miotoksicheskih complications;
• Concomitant use of cyclosporin;
• Women: pregnancy, breast-feeding, the lack of adequate methods of contraception;

For preparation at a daily dose of 40 mg:

• Hypersensitivity to rosuvastatin or any of the components;
• Lactose intolerance, lactase deficiency or glucose-galactose malabsorption (product contains lactose);
• Children up to age 18;
• Simultaneous appointment of cyclosporine;
• Women: pregnancy, breast-feeding, the lack of adequate methods of contraception;
• Liver disease in its active phase, including persistent elevation of serum transaminases and any increase in transaminase activity in serum (more than 3 times the upper limit of normal) patients with risk factors for myopathy / rhabdomyolysis, namely:
• Renal failure, moderate (creatinine clearance less than 60 mL / min);
• Hypothyroidism;
• A personal or family history of muscle disease;
• Miotoksichnost to patients receiving other HMG-CoA reductase inhibitors or fibrates in history;
• Excessive drinking;
• Conditions which can lead to increased plasma concentrations of rosuvastatin;
• Simultaneous reception of fibrates;
• Use in patients Mongoloid race.

Precautions: For preparation at a daily dose of 5 mg, 10 mg and 20 mg:

The presence of the risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, personal or family history of hereditary muscular diseases and previous history of muscular toxicity with other HMG-CoA reductase inhibitors (statins) or fibrates; excessive alcohol consumption; age over 65 years; a condition in which the observed increase in plasma concentrations of rosuvastatin; race (Mongoloid race); co-administration with fibrates (see "Pharmacokinetics" section.) history of liver disease; sepsis; hypotension; extensive surgery, trauma, severe metabolic, endocrine, or water-electrolyte disorders, or uncontrolled seizures.

For preparation at a daily dose of 40 mg:

Renal insufficiency mild severity (creatinine clearance 60 mL / min); age over 65 years; history of liver disease; sepsis; hypotension; extensive surgery, trauma, severe metabolic, endocrine, or water-electrolyte disorders, or uncontrolled seizures.

Patients with hepatic insufficiency

Data or experience with the drug in patients with more than 9 th scores on the Child-Pugh is absent (see. Forums "Pharmacodynamics" and "Cautions").

Pregnancy and during breastfeeding

Rosuvastatin is contraindicated in pregnancy and during breastfeeding.

Women of childbearing age should use adequate contraception methods.

Since cholesterol and other products of cholesterol biosynthesis are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase inhibitors outweigh the benefits of the drug in pregnant women.

In the case of diagnosis of pregnancy during therapy, the drug should be discontinued immediately.

Data on the allocation of rosuvastatin with breast milk are not available, so it is necessary to stop (see. "Contraindications") during breast-feeding taking the drug.

Rosuvastatin Dosage and Administration

Inside, do not chew or crush the tablet, swallowed whole with water. The drug can be administered at any time regardless of mealtime.

Before starting therapy with Rosuvastatin patient must begin to comply with a standard hypocholesterolemic diet and continue to observe her during treatment. The dose should be individualized depending on the goals of therapy and the therapeutic response to treatment, taking into account the current recommendations for the target concentration of lipids.

The recommended initial dose for patients who start taking the drug, or for patients transferred from receiving other HMG-CoA reductase inhibitors, should be 5 or 10 mg Rosuvastatin 1 time per day. When selecting the starting dose should be guided by the individual cholesterol and take into account the possible risk of cardiovascular complications, as well as the need to evaluate the potential risk of side effects. If necessary, the dose may be increased to greater after 4 weeks (see., "Pharmacodynamics" section).

Due to the possibility of side effects while taking a 40 mg dose compared with lower doses of the drug (see. See "Side effect"), increasing the dose to 40 mg after supplementation doses above the recommended starting dose for 4 weeks therapy can be performed only in patients with severe hypercholesterolaemia and at high risk for cardiovascular complications (especially in patients with familial hypercholesterolaemia), who do not have the desired result of therapy was achieved by administration of a dose of 20 mg, and which will be under the supervision of a specialist ( see. "Special instructions" section). Recommended especially careful monitoring of patients receiving the drug at a dose of 40 mg.

Not recommended the appointment of a 40 mg dose in patients not previously go to the doctor.

After 2-4 weeks of treatment and / or increasing the dose of the drug Rosuvastatin need to control lipid metabolism (Dosage adjustment, if necessary). Use of the drug at a higher dose than 40 mg is not justified in view of the increasing side effects in most cases and is not recommended.

Elderly patients

No dose adjustment is required.

Patients with renal failure

In patients with renal insufficiency, mild or moderate dose adjustment is required. In patients with severe renal insufficiency (creatinine clearance less than 30 ml / min.), Use of the drug Rosuvastatin is contraindicated. Do not use this drug at a dose of 40 mg in patients with moderate renal impairment (creatinine clearance 30-60 ml / min.) (See. "Special Instructions" section "Pharmacodynamics"). Patients with moderate renal impairment is recommended initial dose of 5 mg.

Patients with hepatic insufficiency

Rosuvastatin is contraindicated in patients with liver disease in the active phase (see. "Contraindications").

Special populations. Ethnic groups

In the study of rosuvastatin pharmacokinetic parameters in patients belonging to different ethnic groups, noted an increase in systemic concentrations of rosuvastatin among Japanese and Chinese (see. "Special Instructions" section). Keep in mind this fact when administering the drug Rosuvastatin patient data groups. At doses of 10 and 20 mg of the recommended initial dose for patients Mongoloid race is 5 mg. Contraindicated use of the drug at a dose of 40 mg to patients Mongoloid race (see. "Contraindications").

Genetic polymorphism

Carriers genotypes SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) s.421AA was an increase in exposure (AUC) for rosuvastatin, compared with native genotypes SLCO1B1 c.521TT and ABCG2 c.421CC. For patients carrying genotypes s.521CC or s.421AA the recommended maximum dose of the drug Rosuvastatin is 20 mg once daily (see. Forums "Pharmacokinetics", "Special Instructions" and "Interaction with other medicinal products and other forms of drug interactions") .

Patients predisposed to myopathy

Contraindicated use of the drug at a dose of 40 mg in patients with factors that may indicate a predisposition for the development of myopathy (see. "Contraindications"). At doses of 10 and 20 mg of the recommended initial dose for this group of patients is 5 mg (See. "Contraindications").

concomitant therapy

Rosuvastatin is associated with various transport proteins (in particular OATR1V1 and BCRP). When combined drug Rosuvastatin with drugs (such as cyclosporine, some HIV protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and / or tipranavir), increases the concentration of rosuvastatin in the plasma due to interaction with transport proteins, may increase the risk of myopathy (including rhabdomyolysis ) (see. sections "Special instructions" and "interaction with other medicinal products and other forms of drug interactions"). In such cases it is necessary to evaluate the possibility of appointing an alternative therapy or temporary discontinuation of drug Rosuvastatin. If the application of the above-mentioned drugs is necessary, it should weigh the benefits and risks of concomitant therapy with Rosuvastatin and consider reducing the dose ( "Interaction with other medicinal products and other forms of drug interactions," see. Section).

Side effect ofRosuvastatin

Side effects seen when taking Rosuvastatin medication, usually expressed slightly and tested independently. As with other HMG-CoA reductase, the incidence of side effects is essentially dose-dependent.

The incidence of undesirable effects are presented in accordance with the World Health Organization classification: common (> 1/100, <1/10); uncommon (> 1/1000, <1/100); rare (> 1/10000, <1/1000); very rare (<1/10000), unspecified frequency (can not be calculated from the available data).

The immune system:

Rare: hypersensitivity reactions, including angioedema

Endocrine system:

Common: diabetes mellitus type 2

On the part of the central nervous system:

Common: headache, dizziness

On the part of the digestive tract:

Common: constipation, nausea, abdominal pain

Rare: pancreatitis

For the skin:

Uncommon: pruritus, rash, urticaria

From the musculoskeletal system:

Common: myalgia;

Rare: myopathy (including myositis), rhabdomyolysis

other

Common: asthenic syndrome

From the urinary system:

Patients treated with Rosuvastatin can be detected proteinuria. Changes in the amount of protein in the urine (from no or trace amounts to ++ or more) occur in less than 1% of patients treated with 10-20 mg, and about 3% of patients receiving 40 mg. Slight change in the amount of protein in urine observed when receiving a dose of 20 mg. In most cases, proteinuria is reduced or disappears during therapy and means of acute or progression of existing kidney disease.

From the musculoskeletal system:

In applying the drug Rosuvastatin at all doses and in particular when receiving doses greater than 20 mg, reported the following effects on the musculoskeletal system: myalgia, myopathy (including myositis), in rare cases, - rhabdomyolysis with acute renal failure or without .

Dose-dependent increase in the activity of creatine phosphokinase (CPK) was observed in a small number of patients taking rosuvastatin. In most cases it was slight, temporary and asymptomatic. In case of increase of CPK therapy should be stopped (more than 5 times compared with the upper limit of normal) (cm. "Special instructions" section).

Liver

When using rosuvastatin observed a dose-dependent increase in the activity of "liver" transaminases in a small number of patients. In most cases, it is slightly and temporarily asymptomatic.

Laboratory findings

In applying the drug Rosuvastatin also observed the following changes in laboratory parameters: increase of the concentration of glucose, bilirubin, gamma-glutamyl activity, alkaline phosphatase, thyroid dysfunction.

post-marketing use

It reported the following side effects in post-marketing use of the drug Rosuvastatin:

Hematopoietic system

Unspecified frequency: thrombocytopenia

On the part of the digestive tract

Very rare: jaundice, hepatitis

Rare: increased activity of "liver" transaminases

Unspecified frequency: diarrhea

On the part of the musculoskeletal system

Very rare: arthralgia

Unspecified frequency: immune-mediated necrotizing myopathy

Central nervous system

Very rare: loss or reduction of the memory; unspecified frequency - peripheral neuropathy.

The respiratory system

Unspecified frequency: cough, shortness of breath

From the urinary system

Very rare: haematuria

For the skin and subcutaneous fat

Unspecified frequency: Stevens-Johnson syndrome

Reproductive system and breast:

Unspecified frequency - Gynecomastia

other

Unspecified frequency: peripheral edema

With some statins reported the following side effects:

depression, sleep disorders, including insomnia and "nightmarish" dream, sexual dysfunction, hyperglycemia, increasing the concentration of glycated hemoglobin. It was reported about rare cases of interstitial lung disease, especially with long-term use of drugs (see. "Special Instructions" section).

Overdose

At the same time taking multiple daily doses of rosuvastatin pharmacokinetic parameters are not changed.

Symptoms typical for rosuvastatin symptoms are not observed. They represent the effects enhanced and such as those described in "Side effect".

Treatment: No specific treatment of overdosage with rosuvastatin or a specific antidote exists. Recommended timely gastric lavage and symptomatic treatment is necessary to monitor liver function and CK activity, as well as measures aimed at maintaining the function of vital organs and systems; Hemodialysis is ineffective.

Interaction

Inhibitors of transport proteins: rosuvastatin binds to certain transport proteins, in particular, and OATR1V1 VSRP. Concomitant use of drugs that are inhibitors of these transport proteins can be accompanied by an increase in plasma rosuvastatin concentrations and an increased risk of myopathy (see. Table 1 and sections "Dosage and Administration" and "special instructions").

Cyclosporin: while the use of cyclosporin and rosuvastatin rosuvastatin AUC was on average 7-fold higher than the value which is observed in healthy volunteers (see Table 1). No effect on the plasma concentration of cyclosporine. Rosuvastatin is contraindicated in patients receiving tacrolimus (see. "Contraindications").

Protease inhibitors of human immunodeficiency virus (HIV): although the exact mechanism of the interaction is unknown, co-administration of HIV protease inhibitors can cause a considerable increase in exposure to rosuvastatin (see table 1.). Pharmacokinetic Study the simultaneous application of 20 mg of rosuvastatin with a combined preparation comprising two HIV protease inhibitor (400 mg lopinavir / ritonavir 100 mg) in healthy volunteers resulted in approximately two-fold and five-fold increase in AUC (0-24) and Cmax of rosuvastatin, respectively. Therefore, concomitant use of rosuvastatin and HIV protease inhibitors is not recommended (see. Sections "Dosage and administration", "Special Instructions", Table 1).

Gemfibrozil and other lipid-lowering agents: the combined use of gemfibrozil and rosuvastatin increases to 2 times the maximum rosuvastatin concentrations in blood and plasma rosuvastatin AUC (see "Special Instructions" section.). Based on data from specific interaction is not expected pharmacokinetic significant interaction with fenofibrate may pharmacodynamic interaction.

Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g / day) increased risk of myopathy while the use of inhibitors of HMG-CoA reductase, possibly due to the fact that they can cause myopathy when used as monotherapy (see . "Special instructions" section). At the same time taking the drug with gemfibrozil, fibrates, nicotinic acid lipid-lowering doses (more than 1 g / day) in patients recommended initial dose of 5 mg, receive a dose of 40 mg is contraindicated in concomitant use with fibrates (see. Sections "Contraindications", "method dosage and administration "," Special instructions ").

Ezetimibe: simultaneous administration of the drug Rosuvastatin 10 mg of ezetimibe and 10 mg of rosuvastatin AUC accompanied by an increase in patients with hypercholesterolemia (see table 1.). We can not exclude an increased risk of side effects due to the pharmacodynamic interaction between the drug Rosuvastatin and ezetimibe.

Antacids: simultaneous application of rosuvastatin and antacid suspensions containing magnesium and aluminum hydroxide, resulting in decreased plasma rosuvastatin concentrations of about 50%. This effect is less pronounced, if applied through antacids 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin: simultaneous application of erythromycin and rosuvastatin reduces rosuvastatin on AUC and Cmax 20% 30% rosuvastatin. Such interaction may occur due to increased intestinal motility caused by taking erythromycin.

Cytochrome P450 isozymes: results of studies in vivo and in vitro have shown that rosuvastatin is neither an inhibitor or inducer of cytochrome P450 isoenzymes. Furthermore, rosuvastatin is poor substrate for these isoenzymes. It is therefore not expected to interact with rosuvastatin other drugs on the metabolism level, with the participation of cytochrome P450. There were no clinically significant interactions of rosuvastatin with fluconazole (inhibitor of CYP2C9 isoenzymes and CYP3A4) and ketoconazole (inhibitor of CYP2A6 isoenzyme and CYP3A4).

Fusidic acid: studies of the interaction between rosuvastatin and fusidic acid is not carried out; As with other statins, have been received postmarketing reports of rhabdomyolysis with the concomitant use of rosuvastatin and fusidic acid; patients must be monitored and, if necessary, may be a temporary discontinuation of rosuvastatin.

Effect of rosuvastatin on the use of other drugs

Vitamin K antagonists: initiation of therapy with rosuvastatin or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (eg, warfarin), may result in increased international normalized ratio (INR). Cancel rosuvastatin or a reduction in dose may lead to a decrease in INR. In such cases, control of INR.

Oral contraceptives / hormone replacement therapy: the simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and norgestrel AUC of 26% and 34%, respectively. This increase in plasma concentrations should be considered when selecting oral contraceptive doses. Pharmacokinetic data on the simultaneous use of the drug Rosuvastatin and hormone replacement therapy are not available, therefore we can not exclude a similar effect and the application of the combination. However, this combination was widely used during the clinical trials and was well tolerated by patients.

Other drugs: no clinically significant interaction is expected rosuvastatin with digoxin.

special instructions for Rosuvastatin

Renal effects

In patients receiving high doses of the drug Rosuvastatin (generally 40 mg) tubular proteinuria was observed that in most cases was transient. This is not proteinuria showed an acute kidney disease or progression of kidney disease. Patients taking the drug at a dose of 40 mg is recommended to monitor renal function during treatment.

On the part of the musculoskeletal system

In applying the drug Rosuvastatin at all doses and in particular when receiving doses greater than 20 mg, reported the following effects on the musculoskeletal system: myalgia, myopathy, rhabdomyolysis in rare cases.

Determination of creatine kinase activity

Determination of activity of CK should not be carried out after intense exercise or when there are other possible reasons for the increased activity of CK, which may lead to misinterpretation of the results. If the initial activity of CK significantly increased (5 times higher than the upper limit of normal) should be a re-measurement after 5-7 days. Do not start treatment, if a second test confirms the initial activity of CK (higher by more than 5 times the upper limit of normal).

Prior to initiating therapy

In appointing the drug Rosuvastatin, as well as for the appointment of other inhibitors of HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis (sm. see "Precautions") it is necessary to consider the balance of risk and potential benefits of therapy and to conduct the clinical observation.

During therapy

It is necessary to inform the patient about the need for immediate medical posts about cases of sudden appearance of muscle pain, muscle weakness or cramps, especially in combination with malaise and fever. These patients should be to determine the activity of CK. Therapy should be discontinued if CPK activity was significantly increased (more than 5 times compared with the upper limit of normal) or if by muscle symptoms pronounced and cause daily discomfort (even if CK activity increased by no more than 5 times compared upper limit of normal). If the symptoms disappear, and the activity of CK returns to normal, you should consider re-appointment of the drug rosuvastatin, or other inhibitors of HMG-CoA reductase in smaller doses with careful observation of the patient. Routine monitoring of CK activity is not appropriate in the absence of symptoms.

Very rare cases of immune-mediated necrotising myopathy with clinical manifestations of persistent weakness of the proximal muscles and increase the activity of CK in serum during treatment or discontinuation of statins, including rosuvastatin. You may need to conduct additional studies of muscle and nervous system, serology, and immunosuppressive agents therapy.

There was no evidence of increased exposure on skeletal muscle while taking the drug Rosuvastatin and concomitant therapy. However, the reported increase in the number of cases of myositis and myopathy in patients taking other inhibitors of HMG-CoA reductase inhibitor in combination with a fibric acid derivatives including gemfibrozil, cyclosporin, nicotinic acid as lipid-lowering doses (more than 1 g / d.), Azole antifungals, HIV protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with some HMG-CoA reductase. Thus, it is not recommended the simultaneous use of the drug Rosuvastatin and gemfibrozil. It should be carefully weighed balance of risk and potential benefits in the combined use of the drug Rosuvastatin and fibrates or lipid-lowering doses of niacin. Rosuvastatin is contraindicated taking the drug at a dose of 40 mg in conjunction with fibrates (see. Forums "Interaction with other medicinal products and other forms of drug interactions", "Contraindications").

After 2-4 weeks of treatment and / or by increasing the dose required Rosuvastatin control lipid metabolism (dose required correction if necessary).

Liver

It is recommended that the definition of indicators of liver function before treatment and at 3 months after initiation of therapy. Admission Rosuvastatin drug should be discontinued or the dose reduced if the activity of "liver" in serum transaminases exceeding 3 times the upper limit of normal.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the underlying disease therapy should be carried out prior to the start of treatment with Rosuvastatin.

Special populations. Ethnic groups

During pharmacokinetic studies among the Chinese and Japanese patients showed an increase in systemic concentration of rosuvastatin compared with those obtained among Caucasians patients (see. Sections "Dosage and Administration" and "Pharmacokinetics").

HIV protease inhibitors

We do not recommend the combined use of the drug to HIV protease inhibitors ( "see." Interaction with other medicinal products and other forms of interaction "section).

Lactose

The drug should not be used in patients with lactase deficiency patients intolerant to lactose and glucose-galactose malabsorption.

Interstitial lung disease

With some statins, especially for a long time, it was reported a few cases of interstitial lung disease. Manifestations of the disease may be shortness of breath, non-productive cough and deterioration in general health (fatigue, weight loss and fever). For suspected interstitial lung disease should discontinue statin therapy.

Type 2 diabetes

In patients with a glucose concentration of 5.6 to 6.9 mmol / l therapy with Rosuvastatin was associated with an increased risk of developing type 2 diabetes.

Effects on ability to drive and use other mechanisms

There has been no research on the effect of Rosuvastatin drug on ability to drive and use machinery. Caution must be exercised (dizziness, weakness may occur during therapy) while driving or work requiring high concentration and speed of psychomotor reactions.

Release form of Rosuvastatin

Film-coated tablets of 5 mg, 10 mg and 20 mg.

10 tablets in blisters of PVC film and aluminum foil printed patent.

At 3 or 6 contour cell package, along with instructions for use are placed in a pile of cardboard.

Storage conditions of Rosuvastatin

In a dry, dark place at a temperature no higher than 25 ° C.

Keep out of the reach of children.

Shelf life of Rosuvastatin

2 years.

Do not use beyond the expiration date printed on the package.

Conditions of supply of Rosuvastatin from pharmacies

With prescription.