Rosistark® (Rozistark) – instructions for use, composition, drug analogues, dosages, side

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

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

It is subject to limited metabolism (approximately 10%). Rosuvastatin is a rather non-core substrate for metabolism by isoenzymes of the cytochrome P450 system. CYP2C9 is the main isoenzyme involved in the metabolism of rosuvastatin, while the isoenzymes CYP2C19, CYP3A4 and CYP2D6 are less involved in the metabolism.

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

Approximately 90% of the dose taken of rosuvastatin is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin), the remainder is excreted by the kidneys.

The half-life (T1 / 2) is approximately 19 hours.

The half-life does not change with an increase in the dose of the drug. The geometric mean plasma clearance is approximately 50 l / h (coefficient of variation 21,7%). As with other HMG-CoA reductase inhibitors, the cholesterol membrane transporter, which plays an important role in the hepatic elimination of rosuvastatin, is involved in the process of hepatic uptake of rosuvatin.

The systemic exposure of rosuvastatin increases in proportion to the dose. Changes in pharmacokinetic parameters when taking the drug several times a day is not observed.

Absorption and distribution

Cmax of rosuvastatin in plasma is reached 5 hours after ingestion. Absolute bioavailability is approximately 20%.

Rosuvastatin is metabolized primarily by the liver, which is the main site for the synthesis of Chs and the metabolism of Chs-LDL. Vd of rosuvastatin is approximately 134 liters. About 90% of rosuvastatin binds to plasma proteins, mainly with albumin.

It is subject to limited metabolism (approximately 10%). Rosuvastatin is a rather non-core substrate for metabolism by isoenzymes of the cytochrome P450 system. CYP2C9 is the main isoenzyme involved in the metabolism of rosuvastatin, while the isoenzymes CYP2C19, CYP3A4 and CYP2D6 are less involved in the metabolism.

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

Approximately 90% of the dose taken of rosuvastatin is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin), the remainder is excreted by the kidneys. T1 / 2 is approximately 19 hours, does not change with increasing dose. The geometric mean plasma clearance is approximately 50 l / h (coefficient of variation – 21,7%).

Age and gender. Do not have a clinically significant effect on the pharmacokinetic parameters of rosuvastatin.

Ethnic groups. Comparative pharmacokinetics studies showed an approximately twofold increase in the mean plasma AUC and Cmax values ​​in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with those in the Caucasian race. Indians showed an increase in the average values ​​of AUC and Cmax by about 1,3 times. Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics among representatives of the Caucasian and Negroid races.

Liver failure. In patients with various stages of liver failure with 7 points or lower on the Child-Pugh scale, no increase in T1 / 2 of rosuvastatin was detected. However, in 2 patients with 8 and 9 points on the Child-Pugh scale, an increase of T1 / 2 was observed by about 2 times. There is no experience with rosuvastatin in patients with more than 9 Child-Pugh scores.

Genetic polymorphism. HMG-CoA reductase inhibitors, including Rosistark® binds to the transport proteins OATP1B1 (transport polypeptide of organic anions involved in the capture of statins by hepatocytes) and BCRP (efflux transporter). Carriers of genotypes SLCO1B1 (OATP1B1) s.521CC and ABCG2 (BCRP) s.421AA showed an increase in exposure (AUC) to rosuvastatin 1,6 and 2,4 times, respectively, compared with carriers of genotypes SLCO1B1 c.521TT and ABCG2 c.421CC .

Shelf life of the drug Rosistark®

prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease, but with an increased risk of its development (over 50 years old for men and over 60 years old for women, increased concentration of C-reactive protein (≥2 mg / L) in the presence of at least one of the additional risk factors, such as arterial hypertension, low concentration of HDL-C, smoking, a family history of early development of coronary heart disease);

to slow the progression of atherosclerosis as a supplement to the diet in patients who have been shown therapy to reduce the concentration of total Xc and Xc-LDL;

primary hypercholesterolemia (type IIa according to Fredrickson, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb according to Fredrickson) as a supplement to the diet when diet and other non-drug therapies (eg exercise, weight loss) are insufficient;

hypertriglyceridemia (type IV according to Fredrickson) as a supplement to the diet;

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

For tablets 10 and 20 mg

hypersensitivity to rosuvastatin or any of the components of the drug;

liver disease in the active phase, including a persistent increase in the activity of serum transaminases and any increase in the activity of transaminases in the serum by more than 3 times as compared with VGN;

severe renal failure (Cl creatinine lt; 30 ml / min);

simultaneous administration of cyclosporine;

predisposition to the development of myotoxic complications;

childbearing age in women who do not use reliable contraception;

increased blood CPK concentration more than 5 times compared with VGN;

concomitant use with HIV protease inhibitors;

lactose intolerance, lactase deficiency or glucose-galactose malabsorption (because the drug contains lactose);

age up to 18 years (efficacy and safety not established).

moderate renal failure (creatinine Cl lt; 60 ml / min);

myotoxicity in patients receiving other HMG-CoA reductase inhibitors or a history of fibrates;

personal or family history of muscular disease;

conditions that can lead to increased plasma concentrations of rosuvastatin;

simultaneous reception of fibrates;

women of childbearing age who do not use reliable contraception;

With caution: for tablets of 10 and 20 mg – the presence of a risk of myopathy / rhabdomyolysis – renal failure, hypothyroidism; personal or family history of hereditary muscle disease and a previous history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption;

conditions in which there is an increase in the plasma concentration of rosuvastatin; age over 70 years; a history of liver disease; sepsis; arterial hypotension; extensive surgical interventions; injuries severe metabolic, endocrine or water-electrolyte disturbances; uncontrolled epilepsy; race (Mongoloid race); concomitant use of fibrates; simultaneous use with colchicine and ezetimibe;

Patients with liver failure. There are no data on the use of the drug in patients with more than 9 Child-Pugh scores.

At a temperature not higher than 25 ° C.

Keep out of the reach of children.

Do not use after the expiry date printed on the package.

Synonyms of nosological groups

Heading ICD-10ICD-10 disease synonyms
E78.0 Pure HypercholesterolemiaHeterozygous hereditary hypercholesterolemia
Heterozygous non-family hypercholesterolemia
Heterozygous familial hypercholesterolemia
Hypercholesterolemia
Primary hypercholesterolemia
Homozygous familial hypercholesterolemia
Homozygous sitosterolemia
Isolated endogenous hypercholesterolemia
Primary hypercholesterolemia
High cholesterol
High blood cholesterol
Familial hypercholesterolemia
Mixed familial hypercholesterolemia
Phytosterolemia
Endogenous Hypercholesterolemia
E78.1 Pure HyperglyceridemiaHyperglyceridemia
Hypertriglyceridemia
Essential hypertriglyceridemia
Primary hyperlipidemia
Familial endogenous hypertriglyceridemia
Endogenous hypertriglyceridemia
E78.2 Mixed HyperlipidemiaCombined hyperlipidemia
Combined hypercholesterolemia and hypertriglyceridemia
Combined Hypercholesterolemia and Triglyceridemia
E78.5 Hyperlipidemia, unspecifiedAssociated Hypercholesterolemia
Secondary hyperlipoproteinemia
Hyperlipidemia
Type II hyperlipidemia
Hyperlipidemia IIa
Type IIa hyperlipidemia
Hyperlipoproteinemia
Type IIa Hyperlipoproteinemia
Type IIb hyperlipoproteinemia
Combined hypercholesterolemia and hypertriglyceridemia
Correction of lipid metabolism disorders
Increased LDL
I10 Essential (primary) hypertensionHypertension
Arterial hypertension
Crisis arterial hypertension
Arterial hypertension complicated by diabetes
Hypertension
Sudden increase in blood pressure
Hypertensive circulatory disorders
Hypertensive state
Hypertensive crises
Hypertension
Arterial hypertension
Malignant hypertension
Essential hypertension
Hypertonic disease
Hypertensive crises
Hypertensive crisis
Hypertension
Malignant hypertension
Malignant hypertension
Isolated systolic hypertension
Hypertensive crisis
Exacerbation of hypertension
Primary arterial hypertension
Transient arterial hypertension
Essential arterial hypertension
Essential arterial hypertension
Essential hypertension
Essential hypertension
I15 Secondary hypertensionHypertension
Arterial hypertension
Crisis arterial hypertension
Arterial hypertension complicated by diabetes
Hypertension
Vasorenal hypertension
Sudden increase in blood pressure
Hypertensive circulatory disorders
Hypertensive state
Hypertensive crises
Hypertension
Arterial hypertension
Malignant hypertension
Symptomatic hypertension
Hypertensive crises
Hypertensive crisis
Hypertension
Malignant hypertension
Malignant hypertension
Hypertensive crisis
Exacerbation of hypertension
Renal hypertension
Renovascular arterial hypertension
Renovascular hypertension
Symptomatic arterial hypertension
Transient arterial hypertension
I20.0 Unstable AnginaHeberden’s disease
Unstable angina
Angina pectoris unstable
I21 Acute myocardial infarctionLeft ventricular infarction
Q-wave myocardial infarction
Acute myocardial infarction
Non-transmural myocardial infarction (subendocardial)
Acute myocardial infarction
Myocardial infarction with a pathological Q wave and without it
Myocardial infarction transmural
Myocardial infarction complicated by cardiogenic shock
Non-transmural myocardial infarction
The acute phase of myocardial infarction
Acute myocardial infarction
Subacute stage of myocardial infarction
Subacute period of myocardial infarction
Subendocardial myocardial infarction
Coronary Artery Thrombosis (Arteries)
Threatening myocardial infarction
I25.9 Chronic ischemic heart disease, unspecifiedCHD
Coronary atherosclerosis in patients with coronary heart disease
Coronary circulatory failure
I64 Stroke, not specified as hemorrhage or heart attackCulminating stroke
Stroke
Stroke on the go
Microstroke
Brain strokes
Primary stroke
I70 AtherosclerosisAtherosclerosis
Atherosclerosis of peripheral vessels
Atherosclerotic changes
Atherosclerotic vascular changes
Atherosclerotic Disorders
Gangrene spontaneous
Thrombangism obliterans
Frinlander’s disease
Z72.0 Tobacco UseSmoking
Smoking

Indications for use of the drug

– Primary hypercholesterolemia according to the classification of Fredrickson (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet, when diet and other non-drug therapies (for example, exercise, weight loss) are insufficient.

– Family homozygous hypercholesterolemia as a supplement to diet and other lipid lowering therapy (for example, LDL apheresis) or in cases where such therapy is not effective enough.

– Hypertriglyceridemia (type IV according to the classification of Fredrickson) as an addition to the diet.

– 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 LDL cholesterol.

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

: Hypersensitivity to rosuvastatin or any of the components of the drug; liver disease in the active phase, including a persistent increase in the activity of serum transaminase activity and any increase in serum transaminase activity by more than 3 times compared with the upper limit of normal; severe renal failure (CC less than 30 ml / min); myopathy

concomitant use of cyclosporine; in patients predisposed to the development of myotoxic complications; pregnancy and lactation; in women of childbearing age who do not use reliable contraceptives; an increase in the concentration of creatine phosphokinase (CPK) in the blood by more than 5 times compared with the upper limit of the norm;

Pharmacological group

Heading ICD-10ICD-10 disease synonyms
E78.0 Pure HypercholesterolemiaHeterozygous hereditary hypercholesterolemia
Heterozygous non-family hypercholesterolemia
Heterozygous familial hypercholesterolemia
Hypercholesterolemia
Primary hypercholesterolemia
Homozygous familial hypercholesterolemia
Homozygous sitosterolemia
Isolated endogenous hypercholesterolemia
Primary hypercholesterolemia
High cholesterol
High blood cholesterol
Familial hypercholesterolemia
Mixed familial hypercholesterolemia
Phytosterolemia
Endogenous Hypercholesterolemia
E78.1 Pure HyperglyceridemiaHyperglyceridemia
Hypertriglyceridemia
Essential hypertriglyceridemia
Primary hyperlipidemia
Familial endogenous hypertriglyceridemia
Endogenous hypertriglyceridemia
E78.2 Mixed HyperlipidemiaCombined hyperlipidemia
Combined hypercholesterolemia and hypertriglyceridemia
Combined Hypercholesterolemia and Triglyceridemia
E78.5 Hyperlipidemia, unspecifiedAssociated Hypercholesterolemia
Secondary hyperlipoproteinemia
Hyperlipidemia
Type II hyperlipidemia
Hyperlipidemia IIa
Type IIa hyperlipidemia
Hyperlipoproteinemia
Type IIa Hyperlipoproteinemia
Type IIb hyperlipoproteinemia
Combined hypercholesterolemia and hypertriglyceridemia
Correction of lipid metabolism disorders
Increased LDL
I10 Essential (primary) hypertensionHypertension
Arterial hypertension
Crisis arterial hypertension
Arterial hypertension complicated by diabetes
Hypertension
Sudden increase in blood pressure
Hypertensive circulatory disorders
Hypertensive state
Hypertensive crises
Hypertension
Arterial hypertension
Malignant hypertension
Essential hypertension
Hypertonic disease
Hypertensive crises
Hypertensive crisis
Hypertension
Malignant hypertension
Malignant hypertension
Isolated systolic hypertension
Hypertensive crisis
Exacerbation of hypertension
Primary arterial hypertension
Transient arterial hypertension
Essential arterial hypertension
Essential arterial hypertension
Essential hypertension
Essential hypertension
I15 Secondary hypertensionHypertension
Arterial hypertension
Crisis arterial hypertension
Arterial hypertension complicated by diabetes
Hypertension
Vasorenal hypertension
Sudden increase in blood pressure
Hypertensive circulatory disorders
Hypertensive state
Hypertensive crises
Hypertension
Arterial hypertension
Malignant hypertension
Symptomatic hypertension
Hypertensive crises
Hypertensive crisis
Hypertension
Malignant hypertension
Malignant hypertension
Hypertensive crisis
Exacerbation of hypertension
Renal hypertension
Renovascular arterial hypertension
Renovascular hypertension
Symptomatic arterial hypertension
Transient arterial hypertension
I20.0 Unstable AnginaHeberden’s disease
Unstable angina
Angina pectoris unstable
I21 Acute myocardial infarctionLeft ventricular infarction
Q-wave myocardial infarction
Acute myocardial infarction
Non-transmural myocardial infarction (subendocardial)
Acute myocardial infarction
Myocardial infarction with a pathological Q wave and without it
Myocardial infarction transmural
Myocardial infarction complicated by cardiogenic shock
Non-transmural myocardial infarction
The acute phase of myocardial infarction
Acute myocardial infarction
Subacute stage of myocardial infarction
Subacute period of myocardial infarction
Subendocardial myocardial infarction
Coronary Artery Thrombosis (Arteries)
Threatening myocardial infarction
I25.9 Chronic ischemic heart disease, unspecifiedCHD
Coronary atherosclerosis in patients with coronary heart disease
Coronary circulatory failure
I64 Stroke, not specified as hemorrhage or heart attackCulminating stroke
Stroke
Stroke on the go
Microstroke
Brain strokes
Primary stroke
I70 AtherosclerosisAtherosclerosis
Atherosclerosis of peripheral vessels
Atherosclerotic changes
Atherosclerotic vascular changes
Atherosclerotic Disorders
Gangrene spontaneous
Thrombangism obliterans
Frinlander’s disease
Z72.0 Tobacco UseSmoking
Smoking

Dosing and Administration

take orally, do not chew or grind the tablet, swallow whole, washed down with water.

The drug can be used at any time of the day, regardless of food intake.

Before starting treatment, the patient should start a diet with low cholesterol products, which should be continued during the entire treatment period.

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 generally accepted recommendations for target lipid concentrations.

If it is necessary to take the drug in a dose of 5 mg, it is possible to use the drug rosuvastatin in another dosage form or dosage, for example, 5 mg tablets or 10 mg tablets with risk (tablet at a dose of 10 mg should be divided into two parts at risk).

The recommended initial dose of the drug is 5 mg or 10 mg once a day for patients who have not previously taken statins, and for patients transferred to receive this drug after treatment with other HMG-CoA reductase inhibitors. When choosing an initial dose, one should take into account the level of cholesterol in each individual patient and take into account the possible risk of cardiovascular complications, as well as assess the potential risk of side effects. If necessary, after 1 weeks the dose may be increased.

Due to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug, increasing the dose to 40 mg, after an additional dose is higher than the recommended initial dose for 4 weeks of therapy, can be carried out only in patients with severe hypercholesterolemia and with a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia), who, when taking a dose of 20 mg, did not achieve the desired result of therapy, and which will be under the supervision of a doctor (see

After 2-4 weeks of therapy and / or with an increase in the dose of the drug, monitoring of lipid metabolism is necessary, if necessary, the dose should be adjusted.

The dose of the drug should be adjusted if necessary, its combined use with drugs that increase the exposure to rosuvastatin.

If an increase in exposure of 2 times or more is expected, the initial dose of the drug should be 5 mg once a day. You should also adjust the maximum daily dose of the drug so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs that interact with rosuvastatin.

Patients with renal insufficiency

In patients with mild or moderate renal failure, dose adjustment is not required.

In patients with severe renal failure (CC less than 30 ml / min), the use of the drug is contraindicated. The drug at a dose of 40 mg is contraindicated in patients with moderate impaired renal function (CC 30-60 ml / min). For patients with moderate impaired renal function, an initial dose of 5 mg is recommended.

Rosuvastatin binds to various transport proteins, in particular OATP1B1 and BCRP. When the Rosistark drug is used in conjunction with drugs such as cyclosporine, some HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and / or tipranavir, which increase the concentration of rosuvastatin in plasma due to interaction with transport proteins, the risk of myopathy, including rhabdomyolysis ( see sections “Special Instructions” and “Interaction with Other Medicines”).

In such cases, you should evaluate the possibility of prescribing alternative therapy or temporarily stop taking Rosistark. If the use of the above drugs is necessary, you should evaluate the ratio of the benefit and risk of concomitant therapy with Rosistark and consider the possibility of reducing its dose.

Inside, do not chew or grind the tablet, swallow whole, washed down with water. The drug can be used at any time of the day, regardless of food intake.

Before starting treatment, the patient should begin to follow a diet with the use of products with a low content of Xc, which must be continued during the entire treatment period. 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 generally accepted recommendations for target lipid concentrations.

If you need to take the drug in a dose of 5 mg, you can use the drug rosuvastatin in another dosage form or dosage, for example, tablets 5 mg or tablets 10 mg with risk (tablet 10 mg should be divided into two parts according to the risk).

The recommended initial dose of the drug is 5 or 10 mg once a day, both for patients who have not previously taken statins, and for patients transferred to receive this drug after treatment with other HMG-CoA reductase inhibitors. When choosing an initial dose, the level of Xc for each particular patient should be taken into account and the possible risk of cardiovascular complications should be taken into account, as well as the potential risk of side effects. If necessary, after 1 weeks the dose may be increased.

Due to the possible development of side effects when taking a dose of 40 mg (see “Side effects”), increasing the dose to 40 mg, after an additional dose is higher than the recommended initial dose for 4 weeks of therapy, can only be carried out under the supervision of a doctor in patients with severe form of hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia), who, when taking a dose of 20 mg, did not achieve the desired result of therapy and who will be under doctor observance (see.

After 2 – 4 weeks of therapy and / or with an increase in the dose of the drug, monitoring of lipid metabolism indices is necessary; if necessary, the dose should be adjusted.

The dose of the drug should be adjusted if necessary, its joint use with drugs that increase the exposure of rosuvastatin. If exposure is expected to increase by 2 times or more, the initial dose of the drug should be 5 mg 1 once a day. The maximum daily dose of the drug should also be adjusted so that the expected exposure of rosuvastatin does not exceed that for the dose of 40 mg taken without the simultaneous prescription of drugs interacting with rosuvastatin (see “Interaction”, table 1).

Elderly patients. No dose adjustment required.

Patients with liver failure. The drug is contraindicated in patients with liver disease in the active phase (see. “Contraindications”).

Ethnic groups. In patients of the Mongoloid race, an increase in the systemic concentration of rosuvastatin is possible. This fact should be taken into account when prescribing the drug to these groups of patients. When prescribing doses of 10 and 20 mg, the recommended initial dose of the drug for patients of the Mongoloid race is 5 mg. The use of the drug in a dose of 40 mg in such patients is contraindicated (see. “Contraindications”).

Genetic polymorphism. Carriers of genotypes SLCO1B1 (OATP1B1) s.521CC and ABCG2 (BCRP) s.421AA showed an increase in exposure (AUC) to rosuvastatin compared to carriers of genotypes SLCO1B1 C.521TT and ABCG2 C.421CC. For patients carriers of s.521SS or s.421AA genotypes, the recommended maximum dose of Rosistark® is 20 mg once a day (see “Pharmacokinetics”, “Special Instructions” and “Interaction”).

Patients predisposed to myopathy. When prescribing doses of 10 and 20 mg, the recommended initial dose of the drug for patients with a predisposition to myopathy is 5 mg. The use of the drug in a dose of 40 mg in such patients is contraindicated.

Concomitant therapy. Rosuvastatin binds to various transport proteins, in particular OATP1B1 and BCRP. When combined with the use of Rosistark® with drugs (such as cyclosporine, some HIV protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and / or tipranavir), which increase the concentration of rosuvastatin in plasma due to interaction with transport proteins, the risk of myopathy, including rhabdomyolysis, may increase (cm.

“Special Instructions” and “Interaction”). In such cases, the possibility of prescribing alternative therapy or temporarily discontinuing the drug Rosistark® should be assessed. If the use of the above drugs is necessary, you should evaluate the ratio of the benefit and risk of concomitant therapy with Rosistark® and consider the possibility of reducing its dose (see “Interaction”).

Side effects

Side effects associated with taking Rosistark® are usually mild and go away on their own. The incidence of side effects is mainly dose-dependent, as with other HMG-CoA reductase inhibitors.

From the skin: infrequently – itching, rash, urticaria of unspecified frequency – Stevens-Johnson syndrome.

From the digestive tract: often – constipation, nausea, abdominal pain; rarely – pancreatitis very rarely – jaundice, hepatitis; unspecified frequency – diarrhea.

From the side of the central nervous system: often – headache, dizziness; very rarely – polyneuropathy, memory loss.

From the immune system: rarely – hypersensitivity, including angioedema.

From the endocrine system: often – type 2 diabetes mellitus.

Other: often – asthenic syndrome; unspecified frequency – peripheral edema.

From the musculoskeletal system: often – myalgia; rarely – myopathy (including myositis), rhabdomyolysis; unspecified frequency – immune-mediated necrotizing myopathy.

The effect on skeletal muscle causing myalgia, myopathy (including myositis) and, in rare cases, rhabdomyolysis with or without the development of acute renal failure, was observed in patients taking any dose of rosuvastatin, especially when taking doses exceeding 20 mg. A dose-dependent increase in CPK activity was detected in patients taking rosuvastatin, but in most cases these manifestations were minor, asymptomatic and temporary. In the case of an increase in CPK activity by more than 5 times compared with VGN, therapy should be suspended (see. “Special Instructions”).

From the urinary system: when taking rosuvastatin, proteinuria can be observed. Changes in the protein content in the urine (from the absence or presence of trace amounts to a level and above) are observed in less than 1% of patients taking rosuvastatin at a dose of 10 and 20 mg, and in about 3% of patients taking the drug at a dose of 40 mg.

A slight change in the amount of protein in the urine (from the absence or presence of trace amounts to the level) was observed when taking the drug in a dose of 20 mg. In most cases, proteinuria decreased and passed independently during treatment. An analysis of clinical trial data did not reveal a causal relationship between proteinuria and acute or progressive kidney disease. Very rarely – hematuria, microhematuria.

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, this increase is insignificant, asymptomatic and temporary.

Laboratory indicators: when using rosuvastatin, the following changes in laboratory parameters were observed: an increase in the concentration of glucose, bilirubin, activity of GGT, alkaline phosphatase, impaired thyroid function.

From the hemopoietic system: unspecified frequency – thrombocytopenia.

From the respiratory system: unspecified frequency – cough, shortness of breath.

From the reproductive system and the mammary gland: unspecified frequency – gynecomastia.

The following side effects have been reported with some statins: depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction.

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

Side effects associated with taking the drug

are usually mild and go away on their own. The incidence of side effects is mainly dose-dependent in nature, as with other HMG-CoA reductase inhibitors.

On the part of the skin: infrequently: skin itching, rash, urticaria; unspecified frequency: Stevens-Johnson syndrome.

From the digestive tract: often: constipation, nausea, abdominal pain; rarely: pancreatitis; very rarely: jaundice, hepatitis; unspecified frequency: diarrhea.

On the part of the central nervous system: often: headache, dizziness; very rare: polyneuropathy, memory loss.

From the immune system: rarely: hypersensitivity, including angioedema.

From the endocrine system: often: type 2 diabetes.

Other: often: asthenic syndrome; unspecified frequency: peripheral edema.

From the musculoskeletal system: often: myalgia; rarely: myopathy (including myositis), rhabdomyolysis; very rarely: arthralgia; unspecified frequency: immuno-mediated necrotizing myopathy.

Effects on skeletal muscles that cause myalgia, myopathy (including myositis) and, in rare cases, rhabdomyolysis with or without the development of acute renal failure, were observed in patients taking any dose of rosuvastatin, especially when taking doses exceeding 20 mg.

A dose-dependent increase in the activity of creatine phosphokinase (CPK) was detected in patients taking rosuvastatin, but in most cases these manifestations were minor, asymptomatic and temporary. In the case of an increase in CPK activity by more than 5 times compared with the upper limit of the norm, therapy should be suspended (see the section “Special Instructions”).

From the urinary system. When taking rosuvastatin, proteinuria may occur. Changes in the protein content in the urine (from the absence or presence of trace amounts to a level or higher) are observed in less than 1% of patients taking rosuvastatin at a dose of 10 mg and 20 mg, and in about 3% of patients taking the drug at a dose of 40 mg.

A slight change in the amount of protein in the urine, expressed as a change from zero level or the presence of traces to the level, was observed when taking the drug at a dose of 20 mg. In most cases, proteinuria decreased and passed independently during treatment. An analysis of clinical trial data did not reveal a causal relationship between proteinuria and acute or progressive kidney disease.

Very rarely: hematuria, microhematuria.

From the liver. When using rosuvastatin, a dose-dependent increase in the activity of “liver” transaminases is observed in a small number of patients. In most cases, this increase is insignificant, asymptomatic and temporary.

When using rosuvastatin, the following changes in laboratory parameters were observed: an increase in the concentration of glucose, bilirubin, the activity of gamma-glutamyl transpeptidase, alkaline phosphatase, and dysfunction of the thyroid gland.

From the hemopoietic system: unspecified frequency: thrombocytopenia.

From the respiratory system: unspecified frequency: cough, shortness of breath.

From the reproductive system and mammary gland: unspecified frequency: gynecomastia.

When using certain statins, the following side effects were reported: depression, sleep disturbances, including insomnia and “nightmare” dreams, sexual dysfunction.

contraindications

: the presence of a risk of developing myopathy / rhabdomyolysis – renal failure, hypothyroidism; personal or family history of hereditary muscle disease and a previous history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; conditions in which there is an increase in the plasma concentration of rosuvastatin;

age over 70 years; a history of liver disease; sepsis; arterial hypotension; extensive surgical interventions; injuries severe metabolic, endocrine or water-electrolyte disturbances; uncontrolled epilepsy; race (Mongoloid race); concomitant use of fibrates; simultaneous use with colchicine and ezetimibe.

: moderate renal failure (CC more than 60 ml / min); age over 70 years; a history of liver disease; sepsis; arterial hypotension; extensive surgical interventions; injuries severe metabolic, endocrine or water-electrolyte disturbances; uncontrolled epilepsy; simultaneous use with colchicine and ezetimibe.

Composition

Tablets, film-coated1 table.
active substance:
rosuvastatin10 mg
20 mg
40 mg
(in the form of rosuvastatin calcium – 10,4; 20,8 or 41,6 mg, respectively)
excipients: lactose monohydrate – 89,64 / 179,28 / 229,645 mg; MCC – 42,685 / 85,37 / 109,355 mg; crospovidone – 6/12/16 mg; magnesium stearate – 1,275 / 2,55 / 3,4 mg
film sheath: lactose monohydrate – 1,8 / 3,6 / 4,8 mg; hypromellose – 1,26 / 2,52 / 3,36 mg; titanium dioxide – 1,0778 / 2,1555 / 2,874 mg; triacetin – 0,36 / 0,72 / 0,96 mg; quinoline yellow – 0,0022 / 0,0045 / 0,006 mg

contains the active substance: rosuvastatin 10 mg, 20 mg or 40 mg in the form of calcium rosuvastatin 10,4000 mg, 20,8000 mg or 41,6000 mg, respectively.

Excipients: lactose monohydrate – 89,6400 / 179,2800 / 229,6450 mg, microcrystalline cellulose – 42,6850 / 85,3700 / 109,3550 mg, crospovidone – 6,0000 / 12,0000 / 16,0000 mg, magnesium stearate – 1,2750 / 2,5500 / 3,4000 mg;

tablet shell: lactose monohydrate – 1,8000 / 3,6000 / 4,8000 mg, hypromellose – 1,2600 / 2,5200 / 3,3600 mg, titanium dioxide – 1,0778 / 2,1555 / 2,8740 mg, triacetin – 0,3600 / 0,7200 / 0,9600 mg, quinoline yellow – 0,0022 / 0,0045 / 0,0060 mg.

Pregnancy

Rosistark® is contraindicated during pregnancy and during breastfeeding.

Women of reproductive age should use reliable and adequate methods of contraception.

Since cholesterol and other products of cholesterol biosynthesis are of great importance for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase exceeds the use of the drug in pregnant women.

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

There is no data on the release of rosuvastatin with breast milk, therefore, during breastfeeding, the use of the drug should be discontinued.

contraindicated during pregnancy and during breastfeeding.

Since cholesterol and other cholesterol biosynthesis products are of great importance for the development of the fetus, the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of using the drug in pregnant women.

Form of issue

Film-coated tablets, 10 mg: round, biconvex, from light yellow to yellow, engraved with “10” on one side and “15” on the other side.

Film-coated tablets, 20 mg: round, biconvex, from light yellow to yellow, engraved with “20” on one side and “15” on the other side.

Film-coated tablets, 40 mg: round, biconvex, from light yellow to yellow, engraved with “40” on one side and “15” on the other side.

Effect of the use of other drugs on rosuvastatin

Inhibitors of transport proteins: rosuvastatin binds to certain transport proteins, in particular OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in plasma concentration of rosuvastatin and an increased risk of myopathy (see table 1, “Dosage and administration” and “Special instructions”).

Cyclosporine: with the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin increased by 7 times compared with the values ​​obtained from healthy volunteers (see “Contraindications”). Joint use leads to an increase in the concentration of rosuvastatin in blood plasma by 11 times. The simultaneous use of drugs does not affect the concentration of cyclosporine in blood plasma.

Ezetimibe: with the simultaneous use of rosuvastatin and ezetimibe, no changes in the AUC or Cmax of both drugs are observed.
However, the risk of side effects due to the pharmacodynamic interaction between rosuvastatin and ezetimibe cannot be ruled out.

Gemfibrozil and other hypolipidemic agents: the simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax and AUC of rosuvastatin (see “Special instructions”). Based on data from a study of specific interactions, a pharmacokinetically significant interaction with fenofibrate is not expected, but pharmacodynamic interaction is possible.

Gemfibrozil, fenofibrate, other fibrates, and nicotinic acid in lipid lowering doses (1 g / day or more), when used together with HMG-CoA reductase inhibitors, increased the risk of myopathy, possibly due to the fact that they can also cause myopathy when used in as monotherapy. The concomitant use of 40 mg of rosuvastatin and fibrates is contraindicated (see

HIV protease inhibitors: although the exact mechanism of interaction is unknown, the concomitant use of rosuvastatin with HIV protease inhibitors can lead to a significant increase in the exposure of rosuvastatin. In a pharmacokinetic study, while taking 20 mg of rosuvastatin and a combination drug containing two HIV protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir) in healthy volunteers, a 2-fold increase in AUC0-24 and a 5-fold Cmax of rosuvastatin were revealed. Therefore, the simultaneous administration of rosuvastatin and HIV protease inhibitors in the treatment of HIV patients is not recommended.

Antacids: the simultaneous administration of rosuvastatin and suspensions of antacids containing aluminum or magnesium hydroxide can lead to a decrease in the concentration of rosuvastatin in blood plasma by about 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin: concomitant use of rosuvastatin and erythromycin can lead to a decrease in AUC0 – t of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. Such an interaction can be caused by increased intestinal motility due to the administration of erythromycin.

Cytochrome P450 isoenzymes: the results of in vitro and in vivo studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a fairly weak substrate for these isoenzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of the isoenzymes CYP2C9 and CYP3A4) and ketoconazole (an inhibitor of the isoenzymes CYP2A6 and CYP3A4).

Colchicine: cases of myopathy, including rhabdomyolysis, have been reported with the simultaneous use of HMG-CoA reductase inhibitors, including rosuvastatin, and colchicine.

The effect of rosuvastatin on other drugs

Vitamin K antagonists: as with other HMG-CoA reductase inhibitors, starting rosuvastatin therapy or increasing the dose of a drug in patients receiving simultaneously indirect anticoagulants (e.g. warfarin or other coumarin anticoagulants) can lead to an increase in PV (INR). Withdrawal of rosuvastatin or dose reduction may cause a decrease in INR. In such cases, an INR should be monitored.

Oral contraceptives / hormone replacement therapy: concomitant use of rosuvastatin and oral contraceptives can lead to an increase in AUC of ethinyl estradiol and norgestrel by 26 and 34%, respectively. Such an increase in plasma concentration should be considered when choosing a dose of oral contraceptives.

There are no pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy, so a similar effect cannot be ruled out when this combination is used. However, this combination of drugs was widely used in clinical trials and was well tolerated by patients.

Other drugs: no clinically significant interaction is expected with the simultaneous use of rosuvastatin and digoxin.

Interaction with drugs that require dose adjustment of rosuvastatin (see table 1)

The dose of the drug Rosistark® should be adjusted if necessary, its combined use with drugs that increase the exposure of rosuvastatin. If an increase in exposure of 2 times or more is expected, the initial dose of Rosistark® should be 5 mg 1 time per day. You should also adjust the maximum daily dose of Rosistark® so that the expected exposure of rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs that interact with rosuvastatin.

Effect of concomitant therapy on the exposure of rosuvastatin (AUC, data are given in descending order) – results of published clinical studies

Mode of concomitant therapyRosuvastatin regimenChange in AUC of Rosuvastatin
Cyclosporine, 75 – 200 mg 2 times per day, 6 months10 mg 1 once a day, 10 daysIncrease 7,1 times
Atazanavir, 300 mg / ritonavir, 100 mg 1 once a day, 8 days10 mg onceIncrease 3,1 times
Lopinavir, 400 mg / ritonavir, 100 mg 2 times per day, 17 days20 mg 1 once a day, 7 daysIncrease 2,1 times
Gemfibrozil, 600 mg 2 times per day, 7 days80 mg onceIncrease 1,9 times
Eltrombopag, 75 mg 1 once a day, 10 days10 mg onceIncrease 1,6 times
Darunavir, 600 mg / ritonavir 100 mg 2 times per day, 7 days10 mg 1 once a day, 7 daysIncrease 1,5 times
Tipranavir, 500 mg / ritonavir 200 mg 2 times per day, 11 days10 mg onceIncrease 1,4 times
Dronedarone, 400 mg 2 times per dayNo dataIncrease 1,4 times
Itraconazole, 200 mg 1 once a day, 5 days10 or 80 mg onceIncrease 1,4 times
Ezetimibe, 10 mg 1 once a day, 14 days10 mg 1 once a day, 14 daysIncrease 1,2 times
Fosamprenavir, 700 mg / ritonavir, 100 mg 2 times per day, 8 days10 mg onceUnchanged
Aleglitazar, 0,3 mg, 7 days40 mg, 7 daysUnchanged
Silymarin, 140 mg 3 times per day, 5 days10 mg onceUnchanged
Fenofibrate, 67 mg 3 times per day, 7 days10 mg, 7 daysUnchanged
Rifampin, 450 mg 1 once a day, 7 days20 mg onceUnchanged
Ketoconazole, 200 mg 2 times per day, 7 days80 mg onceUnchanged
Fluconazole, 200 mg 1 once a day, 11 days80 mg onceUnchanged
Erythromycin, 500 mg 4 times per day, 7 days80 mg once28% reduction
Baicalin, 50 mg 3 times per day, 14 days20 mg once47% reduction

Film-coated tablets, 10 mg, 20 mg, 40 mg. In a blister of polyamide / aluminum / PVC foil, in consumer packaging made of cardboard, containing 14, 28, 56 or 70 tablets.

Inhibitors of transport proteins: rosuvastatin binds to certain transport proteins, in particular, OATP1B1 and BCRP.

Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in plasma and an increased risk of developing myopathy.

Cyclosporine: with the simultaneous use of rosuvastatin and cyclosporin, the AUC of rosuvastatin increased 7 times compared with the values ​​obtained from healthy volunteers. Joint use leads to an increase in the concentration of rosuvastatin in blood plasma by 11 times. The simultaneous use of drugs does not affect the concentration of cyclosporine in blood plasma.

Ezetimibe: with the simultaneous use of rosuvastatin and ezetimibe, there is no change in AUC or Cmax of both drugs. However, the risk of side effects due to the pharmacodynamic interaction between rosuvastatin and ezetimibe cannot be ruled out.

Gemfibrozil and other lipid-lowering drugs: the simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax and AUC of rosuvastatin. Based on the data of the study of specific interactions, no pharmacokinetically significant interaction with fenofibrate is expected, but pharmacodynamic interaction is possible.

Gemfibrozil, fenofibrate, other fibrates, and nicotinic acid in lipid lowering doses (1 g or more per day) while using HMG-CoA reductase inhibitors increased the risk of myopathy, possibly due to the fact that they can also cause myopathy when used as monotherapy. Concomitant use of 40 mg of rosuvastatin and fibrates is contraindicated.

Overdose

There is no specific treatment for an overdose of rosuvastatin. In case of overdose, it is recommended to carry out symptomatic treatment and support functions of vital organs and systems of the event. Liver function and CPK activity should be monitored. Hemodialysis in this case is probably ineffective.

Specific treatment for drug overdose

does not exist. In case of overdose, it is recommended to carry out symptomatic treatment and supporting functions of vital organs and systems of the event. Liver function and CPK activity should be monitored. Hemodialysis in this case is probably ineffective.

Pharmacodynamics

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, which is a precursor of cholesterol. The main target of the action of rosuvastatin is the liver, where the synthesis of cholesterol (Chs) and LDL catabolism are carried out.

Rosuvastatin increases the number of liver LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which leads to inhibition of the synthesis of VLDL, thereby reducing the total amount of LDL and VLDL.

Rosuvastatin reduces the elevated content of LDL-C, total cholesterol and triglycerides (TG), increases the concentration of HDL-C, and also reduces the concentration of apolipoprotein B (ApoV), Xc-non-HDL, Xc-VLDL, TG-VLDL and increases the concentration of apolipoprotein A (ApoA-I), reduces the ratio of Xs-LDL / Xs-HDL, total Xs / Xs-HDL and Xs-non-HDL / Xs-HDL and the ratio of ApoV / ApoA-I.

The therapeutic effect develops within one week after the start of drug therapy, through 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved through 4 weeks of treatment and is maintained with further regular use of the drug.

Clinical efficacy. Rosuvastatin is effective in adult patients with hypercholesterolemia with or without symptoms of hypertriglyceridemia, regardless of race, gender or age, as well as in the treatment of patients with diabetes mellitus and a hereditary form of familial hypercholesterolemia.

Rosuvastatin is effective in patients with type IIa and IIb hypercholesterolemia according to Fredrickson (the average initial concentration of LDL-C is about 4,8 mmol / l). In 80% of these patients receiving 10 mg of rosuvastatin, the concentration reaches the target values ​​of the level of LDL-C established by the European Atherosclerosis Research Community – less than 3 mmol / L.

As a result of titration of doses to a daily dose of 40 mg (12 weeks of therapy), a decrease in the concentration of LDL-C by 53% is noted. In 33% of patients, an LDL-C concentration of less than 3 mmol / L is achieved that meets the target guidelines of the European Atherosclerosis Study Guide.

In patients with homozygous familial hypercholesterolemia who took rosuvastatin in doses of 20 and 40 mg, the average decrease in the concentration of LDL-C is 22%. In patients with hypertriglyceridemia with an initial concentration of TG from 273 to 817 mg / dl, taking rosuvastatin at a dose of 5 mg to 40 mg once a day for 1 weeks, the concentration of TG in the blood plasma was significantly reduced.

An additive effect is observed in combination with fenofibrate in relation to the content of TG and with nicotinic acid (more than 1 g / day) in relation to the content of HDL-C. In patients with a low risk of developing CHD (a 10-year risk on the Framingham scale is less than 10%), with an average concentration of LDL-C 4 mmol / l (154,5 mg / dl) and subclinical atherosclerosis, which was assessed by the thickness of the intima complex -Media ”of the carotid arteries (TCIM), rosuvastatin at a dose of 40 mg / day significantly slowed the progression rate of maximum TCIM for 12 segments of the carotid artery compared with placebo with a difference of −0,0145 mm / year (95% confidence interval (CI): from −0,0196 to −0,0093; p lt; 0,001).

The study was conducted in patients with a low risk of coronary heart disease, for which a dose of 40 mg is not recommended. A dose of 40 mg should be prescribed only to patients with severe hypercholesterolemia and a high risk of cardiovascular disease.

The results of a study on the use of statins for primary prevention showed that rosuvastatin significantly reduced the risk of developing cardiovascular complications with a relative risk reduction of 44%.

The effectiveness of therapy was noted after 6 months of using the drug. There was a statistically significant decrease of 48% in the combined criterion, including death from cardiovascular diseases, stroke and myocardial infarction, a 54% decrease in the occurrence of fatal or nonfatal myocardial infarction and by 48% in fatal or nonfatal stroke.

special instructions

Renal effects. Proteinuria, mainly of calcium origin, was observed in patients taking high doses of rosuvastatin, in particular 40 mg, which in most cases was periodic or short-term. Such proteinuria does not mean the occurrence of acute or progressive kidney disease.

From the musculoskeletal system. When using the drug Rosistark® in all dosages, and especially when taking the drug in a dose exceeding 20 mg, myalgia, myopathy and, in rare cases, rhabdomyolysis were revealed.

Determination of CPK activity. The study should not be carried out after intense physical exertion or if there are other possible reasons for the increase in CPK activity, which can lead to an incorrect interpretation of the results. If the initial level of CPK is significantly increased (more than 5 times higher than VGN), after 5-7 days, a second measurement should be carried out. Therapy should not be started if a repeated measurement confirms the initial level of CK (5 times higher compared with VGN).

Before starting therapy. Rosistark®, like other HMG-CoA reductase inhibitors, should be used with caution in patients with existing risk factors for myopathy / rhabdomyolysis.

In such patients, the ratio of risk to potential benefit of therapy should be assessed and clinical observation should be carried out throughout the course of treatment.

During therapy. It is recommended that patients be informed of the need to immediately inform the doctor of cases of sudden onset of muscle pain, muscle weakness or cramping, especially in combination with malaise or fever. In such patients, it is necessary to monitor the activity of CPK.

Treatment should be discontinued if CPK activity is more than 5 times higher than VGN or muscle symptoms are pronounced and cause daily discomfort, even if KFK activity is 5 times less than VGN. If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Rosistark® or other HMG-CoA reductase inhibitors in lower doses with careful monitoring of the patient. Regular monitoring of CPK activity in the absence of symptoms is impractical.

Very rare cases of immune-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of the proximal muscles and an increase in the level of CPK in the blood serum during treatment or when discontinuation of statins, including Rosuvastatin. Additional studies of the muscular and nervous systems, serological studies, and therapy with immunosuppressive agents may be required.

There were no signs of increased effects on skeletal muscle when using rosuvastatin and concomitant therapy. However, an increase in cases of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in conjunction with fibric acid derivatives, including gemfibrozil, cyclosporin, nicotinic acid, antifungal drugs, protease inhibitors and macrolide antibiotics.

Gemfibrozil increases the risk of myopathy when used together with certain HMG-CoA reductase inhibitors. Therefore, the simultaneous administration of rosuvastatin and gemfibrozil is not recommended. The ratio of risk and possible benefit should be carefully evaluated when combined with the use of rosuvastatin with fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day).

The concomitant use of rosuvastatin in a dose of 40 mg and fibrates is contraindicated (see “Interaction” and “Side Effects”). 2–4 weeks after the start of treatment and / or with an increase in the dose of the Rosistark® preparation, monitoring of lipid metabolism is necessary, and dose adjustment is necessary if necessary.

Liver. Like other HMG-CoA reductase inhibitors, Rosistark® should be used with extreme caution in patients with a history of alcohol abuse or liver disease. It is recommended to determine liver function indices before the start of therapy and 3 months after the start of therapy. If the activity of hepatic transaminases in blood serum is 3 times higher than VGN, you should stop taking the drug Rosistark® or reduce the dose of the drug (see “Dosage and Administration”).

In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying disease should be carried out before starting treatment with rosuvastatin.

Ethnic groups. In the course of pharmacokinetic studies, an increase in the systemic concentration of rosuvastatin in patients of Chinese and Japanese origin was revealed compared with the indices obtained in patients of the Caucasian race (see “Dosage and Administration” and “Pharmacokinetics”).

HIV protease inhibitors. The simultaneous use of rosuvastatin with HIV protease inhibitors is not recommended (see “Interaction”).

Lactose. The drug should not be used in patients with lactase deficiency, galactose intolerance and glucose-galactose malabsorption.

Interstitial lung disease. When using certain statins, especially for a long time, isolated cases of interstitial lung disease have been reported. Manifestations of the disease can include shortness of breath, dry cough, and general well-being (weakness, weight loss, and fever). If interstitial pulmonary disease is suspected, statin therapy should be discontinued.

Type 2 diabetes mellitus. In patients with a glucose concentration of 5,6 to 6,9 mmol / L, the use of rosuvastatin leads to an increased risk of developing type 2 diabetes.

Influence on the ability to drive vehicles and mechanisms. Studies to study the effect of rosuvastatin on the ability to drive vehicles and mechanisms have not been conducted. Based on the pharmacodynamic properties of the drug, it can be assumed that rosuvastatin should not have such an effect, but it should be borne in mind that dizziness may occur during treatment.

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Svetlana Borszavich

General practitioner, cardiologist, with active work in therapy, gastroenterology, cardiology, rheumatology, immunology with allergology.
Fluent in general clinical methods for the diagnosis and treatment of heart disease, as well as electrocardiography, echocardiography, monitoring of cholera on an ECG and daily monitoring of blood pressure.
The treatment complex developed by the author significantly helps with cerebrovascular injuries and metabolic disorders in the brain and vascular diseases: hypertension and complications caused by diabetes.
The author is a member of the European Society of Therapists, a regular participant in scientific conferences and congresses in the field of cardiology and general medicine. She has repeatedly participated in a research program at a private university in Japan in the field of reconstructive medicine.

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