Crestor pills 10mg, 126pcs

Composition

Each tablet contains an Active ingredient:

rosuvastatin 10 in the form of rosuvastatin calcium.

Auxiliary substances:

lactose monohydrate 89.50 mg;

microcrystalline cellulose 29.82 mg;

calcium phosphate 10.90 mg;

crospovidone 7.50 mg;

magnesium stearate 1.88 mg;

Tablet shell:

lactose monohydrate 1.80 mg;

hypromellose 1.26 mg;

triacetin (glycerol triacetate) 0.36 mg;

titanium dioxide 1.06 mg;

iron oxide red dye 0.02 mg

Pharmacological action

Pharmacotherapy group: Hypolipidemic agent-HMG-CoA reductase Inhibitor ATX Code: C10AAFarmacodynamics: Mechanism of 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 cholesterol synthesis and catabolism of low-density lipoproteins (LDL) are 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 the synthesis of very low-density lipoproteins (VLDL), thereby reducing the total amount of LDL and VLDL.

Pharmacodynamics

Crestor ® reduces elevated concentrations of LDL cholesterol (LDL-C) total triglyceride cholesterol (TG) increases the concentration of high-density lipoprotein cholesterol (HDL-C) and also reduces the concentration of apolipoprotein B (apoB) HDL-C VLDL-C TG-VLDL and increases the concentration of apolipoprotein A-1 (ApoA-1) (see Tables 1 and 2) reduces the ratio of LDL-C/HDL total cholesterol/HDL and HDL-C/HDL-C and the apoB/ApoA-1 ratio. The therapeutic effect develops within one week after starting therapy with Crestor® after 2 weeks of treatment 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.

Table 1. Dose-dependent effect in patients with primary hypercholesterolemia (Fredrickson type IIa and IIb) (mean adjusted percentage change compared to baseline).

Dosage	Number of patients	with cs-PNP	Total		Cholesterol HDL-C tg	HDL-C Non-HDL	ApoV	Apo A-1
Placebo	13-7-5			3-3-7-3				0
5 mg	17-45-33			13-35-44-38				4 ‘
10 mg	17-52-36			14-10-48-42				4
20 mg	17-55-40			8-23-51-46				5
40 mg	18-63-46			10-28-60-54				0

Table 2. Dose-dependent effect in patients with hypertriglyceridemia (Fredrickson type IIb and IV) (mean percentage change from baseline).

Dosage	Number of	patients with tg	-ldl-c	Total	Cholesterol HDL-C-Non-HDL	C-VLDL	tg-VLDL
Placebo	26	1	5	1-3		2	2	6
5 mg	-25	-21	-28	-24	3-29-25-24
10 mg	23-37-45-40				8-49-48-39
20 mg	27-37-31-34				22-43-49-40
40 mg	25-43-43-40				17-51-56-48

Clinical efficacy

Crestor® is 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 Fredrickson type IIa and IIb hypercholesterolemia (mean baseline LDL-C concentration of about 48 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 Crestor® at a dose of 20-80 mg, there is a positive dynamics of lipid profile indicators (a study involving 435 patients). After titration to a daily dose of 40 mg (12 weeks of therapy), the LDL-C concentration decreased by 53%. In 33% of patients, an LDL-C concentration of less than 3 mmol/l is achieved.

In patients with homozygous familial hypercholesterolemia taking Crestor® at a dose of 20 mg and 40 mg, the average decrease in LDL-C concentration is 22%. In patients with hypertriglyceridemia with an initial TG concentration of 273 to 817 mg / dl treated with Crestor® at a dose of 5 mg to 40 mg once a day for 6 weeks, the concentration of TG in blood plasma significantly decreased (see table 2). An additive effect is observed in combination with fenofibrate in relation to the content of triglycerides and with nicotinic acid in lipid-lowering doses in relation to the content of HDL-C (see also the section “Special instructions”).

In the METEOR study involving 984 patients aged 45-70 years with a low risk of developing coronary heart disease (CHD) (10-year Framingham scale risk of less than 10%) with an average LDL-C concentration of 40 mmol / L (1545 mg / dl) and subclinical atherosclerosis (which was assessed by the thickness of the carotid intima-media complex-MCI), the effect of rosuvastatin on the thickness of the intima-media complex was studied. Patients received either rosuvastatin 40 mg / day or placebo for 2 years. Rosuvastatin therapy significantly slowed the rate of progression.maximum IMI for 12 carotid artery segments compared to placebo with a difference of -00145 mm / year [95% confidence interval -00196 to-00093; p

Compared to baseline values, the maximum IMT value decreased by 00014 mm/yr (012%/yr (unreliable difference))in the rosuvastatin group compared to an increase of 00,131 mm / yr (112% / yr (p To date, no direct relationship has been demonstrated between a reduced IMT and a reduced risk of cardiovascular events. The METEOC study was conducted in patients with a low risk of coronary heart disease for whom the dose of Crestor® 40 mg is not recommended. The 40 mg dose should not be given to patients with severe hypercholesterolemia and a high risk of cardiovascular disease (CVD).

Results of the UPITER study (Justification for the use of statins for primary care. prevention: an interventional study evaluating rosuvastatin) in 17,802 patients showed that rosuvastatin significantly reduced the risk of developing cardiovascular complications (252 in the placebo group compared to 142 in the rosuvastatin group) (p The effectiveness of therapy was noted after the first 6 months of using the drug. There was a statistically significant 48% reduction in the combined criterion that included death from cardiovascular causes stroke and myocardial infarction (risk ratio: 052 95% confidence interval 040-068 p Overall mortality was reduced by 20% in the rosuvastatin group (risk ratio: 080 95% confidence interval 067-097 p=002). The safety profile of patients taking rosuvastatin 20 mg was generally similar to that of the placebo group.

Pharmacokinetics:

Absorption and distribution

The maximum concentration of rosuvastatin in blood plasma is reached approximately 5 hours after oral use. Absolute bioavailability is approximately 20%.

Rosuvastatin is primarily metabolized 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. 11 Approximately 90% of rosuvastatin is bound to plasma proteins, mainly albumin.

Metabolism

It undergoes a limited metabolism (about 10%). Rosuvastatin is a non-core substrate for metabolism by cytochrome P450 enzymes. The main isoenzyme involved in the metabolism of rosuvastatin is isoenzyme SUR 2 C 9. Isoenzymes SUR 2 C 19 SURZA 4 and SUR 206 are involved in the metabolism to a lesser extent. The main identified metabolites of rosuvastatin are N-desmethylrosuvastatin and lactone metabolites. N-desmethylrosuvastatin is approximately 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 and the rest by its metabolites.

Deduction

Approximately 90% of the rosuvastatin dose is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin).

The remaining part is excreted by the kidneys. The plasma half-life (T 1/2) is approximately 19 hours. The half-life does not change with increasing dose of the drug. The average geometric plasma clearance is approximately 50 l / h (coefficient of variation 217%). As in the case of other HMG-CoA reductase inhibitors, the process of”hepatic” uptake of rosuvastatin involves a membrane cholesterol transporter that plays an important role in the hepatic elimination of rosuvastatin.

Linearity

Systemic exposure to rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily use.

Special patient populations.

Age and gender

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

Ethnic groups

Pharmacokinetic studies showed an approximately twofold increase in the median AUC (area under the concentration-time curve) and Cmax (maximum plasma concentration) of rosuvastatin in patients of the Mongolian race (Japanese, Chinese, Filipino, Vietnamese, and Korean) compared with Caucasians; in Hindus, the median AUC and Cmax increased by 13 times. Pharmacokinetic analysis revealed no clinically significant differences in pharmacokinetics between Caucasians and Negroes.

Kidney failure

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

Liver failure

In patients with various stages of hepatic insufficiency, there was no increase in the half-life of rosuvastatin in patients with 7 points or lower on the Child-Pugh scale. In two patients with Child-Pugh scores 8 and 9, the elimination half-life was increased at least 2-fold. There is no experience of using rosuvastatin in patients with more than 9 points on the Child-Pugh scale.

Genetic polymorphism

HMG-CoA reductase inhibitors, including Crestor, bind to the transport proteins OATP 1 In 1 (an organic anion transport polypeptide involved in the uptake of statins by hepatocytes) and BCRP (an efflux transporter). Carriers of genotypes SLCO1 B 1 (OATR 1 B 1) p. 521 CC and ABSG2 (VCR) p. 421 AA showed an increase in exposure (AUC) to rosuvastatin by 16 and 24 times, respectively, compared with carriers of genotypes SLCO1 B 1 p. 521 TT and ABSG2 p. 421 CC.

Indications

-Fredrickson’s primary hypercholesterolemia (type IIa including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) 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 artery disease but with an increased risk of its development (the age of 50 years for men and over 60 years of age 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 concentration of HDL-C non-Smoking family history of early CHD).

Use during pregnancy and lactation

Crestor® is contraindicated during pregnancy and lactation.

Women of reproductive age should use adequate methods of contraception.

Since cholesterol and other products of cholesterol biosynthesis are important for fetal development, the potential risk of HMG-CoA reductase inhibition exceeds the benefit of using the drug in pregnant women.

If pregnancy occurs during therapy, the drug should be discontinued immediately.

There are no data on the excretion of rosuvastatin in breast milk, so the drug should be discontinued during breastfeeding.

Contraindications

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

– lactose intolerance lactase deficiency or glucose-galactose malabsorption (product contains lactose);

– children’s age up to 18 years;

– 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 renal dysfunction (CC less than 30 ml/min);

myopathy;

– concomitant use of cyclosporine;

– in women: pregnancy, lactation, the lack of adequate methods of contraception;

– patients predisposed to the development of myotoxicity complications.

With caution:

Risk of developing myopathy/rhabdomyolysis – renal insufficiency hypothyroidism personal or family history of hereditary muscle diseases and previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; age over-65 years; conditions with increased plasma concentrations of rosuvastatin; race (Mongoloid race); concomitant use with fibrates (see the section “Treatment with rosuvastatin”). Pharmacokinetics”); a history of liver disease; sepsis; hypotension; extensive surgery; severe metabolic endocrine or electrolyte disorders or uncontrolled seizures.

Side effects

Side effects observed when taking Crestor® 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.

The frequency of occurrence of undesirable effects is presented as follows:

common (> 1/100 >< 1/10); infrequent (> 1/1000 < 1/10); infrequent (>< 1/100); rare (> 1/10000 < 1/100); rare (>< 1/1000); very rare (

The immune system

Rarely: hypersensitivity reactions including angioedema

Endocrine System

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

From the musculoskeletal system

Often: myalgia

Rarely: myopathy (including myositis) rhabdomyolysis

Other

Frequently: asthenic syndrome

From the urinary system

Proteinuria may occur in patients treated with Crestor. 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, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or progressive existing kidney disease.

From the musculoskeletal system

The following effects on the musculoskeletal system have been reported with the use of Crestor® in all doses, and especially 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 is observed in a small number of patients taking rosuvastatin. In most cases, it was slightly 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 (see the section “Special instructions”).

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 slightly asymptomatic and temporary.

Laboratory parameters

When using Crestor®, the following changes in laboratory parameters were also observed: increased glucose bilirubin concentration gamma-glutamyltranspeptidase activity alkaline phosphatase thyroid function disorders.

Post-marketing application

The following side effects have been reported with post-marketing use of Crestor®::

From the hematopoietic system

Unspecified frequency: thrombocytopenia

From the digestive tract

Very rare: jaundice hepatitis

Rare: increased activity of “hepatic” transaminases

Unspecified frequency: diarrhea

From the musculoskeletal system

Very rare: arthralgia

Unspecified frequency: immuno-mediated necrotizing myopathy

From the central nervous system

Very rare: memory loss or decline

Unspecified frequency: peripheral neuropathy

Respiratory system disorders

Unspecified frequency: cough shortness of breath

From the urinary system

Very rare: hematuria

From the side of the skin and subcutaneous fat

Unspecified frequency: Stevens-Johnson syndrome

On the part of the reproductive system and breast

Unspecified frequency: gynecomastia

Other services

Unspecified frequency: peripheral edema

The following side effects have been reported with some statins: depression sleep disorders including insomnia and “nightmarish” dreams sexual dysfunction hyperglycemia increased concentration of glycosylated hemoglobin. Isolated cases of interstitial lung disease have been reported, especially with long-term drug use.

Interaction

Effect of other medications on rosuvastatin

Transport protein inhibitors: rosuvastatin binds to some transport proteins, in particular to OATP1 In 1 and OTP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in plasma and an increased risk of developing myopathy (see Table 3 and sections “Dosage and use” and “Special Instructions”).

Cyclosporine: with the simultaneous use of rosuvastatin and cyclosporine A, the rosuvastatin level was on average 7 times higher than that observed in healthy volunteers (see Table 3). It does not affect the plasma concentration of cyclosporine. Krsstor® is contraindicated in patients taking cyclosporine (see section “Contraindications”).

Human immunodeficiency virus (HIV)protease inhibitors: despite the fact that the exact mechanism of interaction is unknown, co-use of HIV protease inhibitors can lead to a significant increase in exposure to rosuvastatin (see Table 3). A pharmacokinetic study on the simultaneous use of 20 mg of rosuvastatin with a combination drug containing two HIV protease inhibitors (400 mg of lopinavir/100 mg of ritonavir) in healthy volunteers resulted in approximately a twofold and fivefold 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 use” and “Special instructions” in Table 3).

Gemfibrozil and other lipid-lowering agents: 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 (see the section “Special instructions”). Based on data on a specific interaction, no pharmacokinetically significant interaction with fenofibrate is expected. Possible pharmacodynamic interaction.

Gemfibrozil fenofibrate other fibrates and lipid-lowering doses of nicotinic acid increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy (see section “Special instructions”). 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 co-administered with fibrates (see the sections “Contraindications” “Method of use and doses” “Special instructions”).

Ezetimibe: concomitant use of Crestor® at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see Table 3). An increased risk of side effects due to the pharmacodynamic interaction between Crestor and ezetimibe cannot be excluded.

Antacids: concomitant use of rosuvastatin and antacid suspensions containing magnesium and aluminum 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: simultaneous use of rosuvastatin and erythromycin leads to a decrease in the AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by taking erythromycin.

Cytochrome P 450 isoenzymes: The results of in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P 450 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 SUR 2 A 9 and SURZA 4 isoenzymes) and ketoconazole (an inhibitor of the SUR 2 A 6 and SURZA 4 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 closely monitored. If necessary, it is possible to temporarily stop taking rosuvastatin.

Drug interactions that require dose adjustment of rosuvastatin (see table 3)

The dose of Crestor® should be adjusted if it is necessary to use it together with drugs that increase exposure to rosuvastatin. You should read the instructions for use of these drugs before prescribing them together with Crestor®. If exposure is expected to increase by a factor of 2 or more, the initial dose of Crestor should be 5 mg once daily. It is also necessary to adjust the maximum daily dose of Crestor® so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without simultaneous use of drugs interacting with rosuvastatin. For example, the maximum daily dose of Crestor® when used concomitantly with gemfibrozil is 20 mg (19-fold increase in exposure) with ritonavir/atazanavir-10 mg (31-fold increase in exposure).

Table 3. Effect of concomitant therapy on exposure to rosuvastatin (AUC data are given in descending order) – results of published clinical trials

Concomitant therapy regimen	Rosuvastatin treatment regimen	Change in the AUC of rosuvastatin
Cycloporin 75-200 mg 2 times a day. 6 months.	10 mg once a day for 10 days	71x increase
Atazanavir 300 mg / ritonavir 100 mg once daily for 8 days	10 mg once	31x increase
Simeprevir 150 mg once a day for 7 days	10 mg once	28x magnification
Lopinavir 400 mg / ritonavir 100 mg twice daily for 17 days	20 mg once daily for 7 days	21x increase
Clopidogrel 300 mg (loading dose) then 75 mg after 24 hours	20 mg once	2-fold increase
Gemfibrozil 600 mg 2 times daily for 7 days	80 mg once	19x increase
Eltrombopag 75 mg once a day for 10 days	10 mg once	16x magnification
Darunavir 600 mg / ritonavir 100 mg once daily for 7 days	10 mg once daily for 7 days	15x magnification
Tipranavir 500 mg / ritonavir 200 mg twice daily for 11 days	10 mg once	14x magnification
Dronedarone 400 mg 2 times a day.	No data available	14x magnification
Itraconazole 200 mg once a day for 5 days	10 mg or 80 mg once	14x magnification
Ezetimibe 10 mg once daily for 14 days	10 mg once daily for 14 days	12x magnification
Fosamprenavir 700 mg / ritonavir 100 mg 2 times a day for 8 days	10 mg once	No changes
Aleglitazar 03 mg 7 days	40 mg 7 days	No changes
Silymarin 140 mg 3 times a day for 5 days	10 mg once	No changes
Fenofibrate 67 mg 3 times a day 7 days	10 mg 7 days	No changes
Rifamiin 450 mg once a day for 7 days	20 mg once	No changes
Ketoconazole 200 mg 2 times a day for 7 days	80 mg once	No changes
Fluconazole 200 mg once a day for 11 days	80 mg once	No changes
Erythromycin 500 mg 4 times a day for 7 days	80 mg once	28% reduction
Baikalin 50 mg 3 times a day for 14 days	20 mg once	47% reduction

Effect of rosuvastatin on other medications

Vitamin K antagonists: starting rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin) It can lead to an increase in the International Normalized Ratio (INR). Discontinuation of rosuvastatin or a reduction in the dose of the drug may lead to a decrease in INR. In such cases, monitoring of INR is recommended.

Oral contraceptives/Hormone replacement 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.

There are no pharmacokinetic data on the concomitant use of Crestor® and hormone replacement therapy, so 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.

How to take, course of use and dosage

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 food intake. Before starting Crestor therapy, the patient should start following 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 Crestor® once a 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 to 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). patients who did not achieve the desired result of therapy when taking a dose of 20 mg and who will be under the supervision of a specialist. 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 when increasing the dose of Crestor®, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required).

Elderly patients

No dose adjustment is required.

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 Crestor® 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

Crestor® 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 Crestor® 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.

Genetic polymorphism

In carriers of the SLCO1 genotypes%^%B%^%1 (OATR%^%1%^%B%^% 1) p. 521%^%CC and ABSG2 (BCR) p. 421%^%AA showed an increase in exposure (AUC) to rosuvastatin compared to carriers of the SLCO1 genotypes%^%In%^%1 S. 521%^%TT and ABSG2 s.421 SS. For patients who are carriers of genotypes C. 521 CC or C. 421 AA The recommended maximum dose of Crestor is 20 mg once daily.

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, OATP1 In 1 and BCRP). Co-use of Crestor with medicinal products (such as cyclosporine, some 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). You should read the instructions for use of these drugs before prescribing them together with Crestor®. In such cases, the possibility of prescribing alternative therapy or temporarily stopping the use of Crestor®should be evaluated. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with Crestor® should be evaluated and the possibility of reducing its dose should be considered.

Overdose

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

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.

Description

10 mg tablets: round, biconvex tablets covered with a pink film shell, with the inscription “ZD4522 10” on one side.

Special instructions

Renal effects

In patients receiving high doses of Crestor® (mainly 40 mg), tubular proteinuria was observed, which in most cases was transient. Such proteinuria was not indicative of acute kidney disease or progressive 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

The following effects on the musculoskeletal system have been reported with the use of Crestor® in all doses and in particular with doses exceeding 20 mg: myalgia, myoathia, in rare cases, rhabdomyolysis.

Determination of creatine phosphokinase

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. 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

Caution should be exercised when prescribing Crestor®, as well as when prescribing other HMG-CoA reductase inhibitors, in patients with existing risk factors for myopathy/rhabdomyolysis (see section “With caution”), the risk-benefit ratio of therapy should be considered and clinical monitoring should be carried out.

During therapy

The patient should be informed of the need to immediately inform the doctor about cases 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 higher than the upper limit of normal) or if muscle symptoms are severe and cause daily discomfort (even if CKD activity is increased no more than 5 times higher than the upper limit of normal). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Crestor 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 immuno – mediated necrotizing myopathy with clinical manifestations of persistent weakness of the proximal muscles and increased activity of CPK in the blood serum were noted during treatment or upon discontinuation of statins, including rosuvastatin. Additional studies of the muscular and nervous system, serological studies, and immunosuppressive therapy may be required.

There were no signs of increased exposure to skeletal muscle when taking Crestor® and concomitant therapy. However, an increase in the incidence of myositis and myopathy has been reported in patients taking 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, concomitant use of Crestor and gemfibrozil is not recommended. The risk-benefit ratio should be carefully weighed when using Crestor® in combination with fibrates or lipid-lowering doses of nicotinic acid. It is contraindicated to take Crestor® at a dose of 40 mg together with fibrates (see the sections “Interaction with other drugs and other forms of drug interaction “”Contraindications”).

In 2-4 weeks after the start of treatment and/or when increasing the dose of Crestor®, monitoring of lipid metabolism parameters is necessary (and if necessary, dose adjustment is required).

The liver

It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. Taking Crestor® 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 Crestor®.

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 Caucasian patients (see the sections “Dosage and use” and “Pharmacokinetics”).

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 lactase deficiency, galactose intolerance and glucose-galactose malabsorption.

Interstitial lung disease

Isolated cases of interstitial lung disease have been reported with the use of certain statins, especially for a long time. Symptoms of the disease may include shortness of breath, 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 glucose concentrations between 56 and 69 mmol/L, Crestor therapy was associated with an increased risk of developing type 2 diabetes mellitus.

Influence on the ability to drive vehicles and mechanisms:

No studies have been conducted to investigate the effect of Crestor® on the ability to drive a vehicle and use mechanisms. Caution should be exercised when driving vehicles or working at work that requires increased concentration of attention and speed of psychomotor reactions (dizziness may occur during therapy).

Storage conditions

At a temperature not exceeding 30°C, out of the reach of children.

Shelf

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

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets