Rozistark pills 20mg №28

Indications

- 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 (for example, physical exercises, weight loss) are insufficient;

- a homozygous form of hereditary hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (for example, LDL-apheresis) or in cases when such therapy is not effective enough;

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

- 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;

- reducing the risk of major cardiovascular complications (cardiovascular death, stroke, heart attack, unstable stenocardia and arterial revascularization) in adult patients with risk factors for cardiovascular complications of atherosclerosis (such as elevated C-reactive protein, age, arterial hypertension, low concentration of HDL-HDL, smoking and a family history of early onset CHD);

- 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 (age over 50 years for men and over 60 years 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 hypertension, low concentrations of HD-C, HDL, smoking, family history of early development of CHD).

Dosage and administration

The drug is taken orally. The pill should be swallowed whole, washed down with water, not chewed or crushed. The drug can be taken at any time of the day, regardless of the meal.

Before starting treatment, the patient should begin to follow a diet with foods that are low in cholesterol, which should be continued throughout the entire period of treatment.

The dose of the drug should be selected individually depending on the goals of therapy and the response to treatment, taking into account modern generally accepted recommendations on target lipid concentrations.

If you need to use the drug in a dose of 5 mg, it is recommended to use Rosuvastatin in another dosage form or dosage, for example, 5 mg pills or 10 mg pills with a risk (a pill at a dose of 10 mg should be divided into two parts according to risk).

The recommended initial dose of the drug is 5 mg or 10 mg 1 time / day for patients who have not previously taken statins, and for patients transferred to the use of this drug after therapy with other HMG-CoA reductase inhibitors.When choosing the initial dose, cholesterol levels should be taken into account in each individual patient and the possible risk of cardiovascular complications should be taken into account, as well as the potential risk of side effects should be evaluated. If necessary, after 4 weeks the dose may be increased.

Due to the possible development of side effects with the use of the drug at a dose of 40 mg, compared with lower doses of the drug, titration to a maximum dose of 40 mg during 4 weeks of therapy can be carried out only in patients with severe hypercholesterolemia and with a high risk of cardiac vascular complications (especially in patients with hereditary hypercholesterolemia) in whom the desired effect of therapy was not achieved with the use of the drug at a dose of 20 mg, and which will be under the supervision of a physician.

When prescribing the drug in a dose of 40 mg, careful monitoring of the patient is recommended. The prescription of the drug in a dose of 40 mg is not recommended for patients who have not previously consulted a doctor.

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 time / day.The maximum daily dose of the drug should also be adjusted so that the expected exposure of rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous prescription of drugs interacting with rosuvastatin (see the section "Interaction with other drugs" Table 1).

Elderly patients no dose adjustment required.

Have patients with mild to moderate renal failure dose adjustment is not required. Have patients with severe renal failure (CC <30 ml / min) use of the drug is contraindicated. Patients with moderate renal impairment an initial dose of 5 mg is recommended. The drug at a dose of 40 mg is contraindicated in patients with moderate renal dysfunction (CC 30-60 ml / min).

The drug is contraindicated patients with liver disease in the active phase.

Have Mongoloid patients may increase the systemic concentration of rosuvastatin. This fact should be taken into account when prescribing the drug to these groups of patients. When prescribing the drug in doses of 10 mg 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 is contraindicated in such patients.

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

Side effect

Side Effects Associated with Taking Rozistark ^®usually moderately pronounced and pass on their own. The frequency of side effects is mainly dose-dependent in nature, as with the use of other HMG-CoA reductase inhibitors.

The following classification is used to indicate the frequency of side effects: often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10 000 and <1/1000), very rarely (<1/10 000), unspecified frequency (cannot be calculated from available data).

On the part of the immune system: rarely, hypersensitivity, including angioedema.

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

Hemic and lymphatic: unspecified frequency - thrombocytopenia.

Gastrointestinal: often - constipation, nausea, abdominal pain; rarely - pancreatitis.

Liver: with the use of 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.

On the part of the endocrine system: often - type 2 diabetes, thyroid dysfunction.

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

Action on skeletal muscle causing myalgiamyopathy (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 in excess of 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 transient. In the case of increased activity of CPK more than 5 times compared with VGN therapy should be suspended.

From the urinary system: when receiving rosuvastatin, proteinuria can be observed. Changes in urine protein content (from the absence or presence of trace amounts to ++ and above) are observed in less than 1% of patients taking rosuvastatin at a dose of 10 mg and 20 mg, and 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 in a change from the zero level or the presence of traces to the level of +, was observed when taking the drug in a dose of 20 mg. In most cases, proteinuria decreased and independently passed on during the treatment. When analyzing data from clinical studies revealed no causal relationship between proteinuria and acute or progressive kidney disease.

From the skin: infrequently - pruritus, rash, urticaria.

From the reproductive system and mammary glands: unspecified frequency - gynecomastia.

Laboratory values: increasing the concentration of glucose, bilirubin, activity of GGT, alkaline phosphatase.

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

When using some statins, the following side effects were reported: depression, sleep disorders, including insomnia and nightmares, sexual dysfunction.

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

Contraindications

For pills 10 and 20 mg

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

- renal failure severe (CC <30 ml / min);

- myopathy;

- simultaneous administration of cyclosporine;

- patients predisposed to the development of myotoxic complications;

- women of reproductive age who do not use reliable contraceptives;

- pregnancy;

- lactation period (breastfeeding);

- age up to 18 years (efficacy and safety have not been established);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (since the preparation contains lactose);

- Hypersensitivity to rosuvastatin or any of the components of the drug.

For 40 mg tablets

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

- renal failure of moderate severity (CC <60 ml / min);

- myopathy;

- simultaneous administration of cyclosporine;

- myotoxicity against the background of taking other HMG-CoA reductase inhibitors or fibrates in history;

- hypothyroidism;

- personal or family history of muscular diseases;

- excessive use of alcohol;

- conditions that can lead to an increase in the concentration of rosuvastatin in the blood plasma;

- simultaneous reception of fibrates;

- women of childbearing age who do not use reliable contraceptives;

- pregnancy;

- lactation period (breastfeeding);

- age up to 18 years (efficacy and safety have not been established);

- patients of the Mongoloid race;

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (since the preparation contains lactose);

- Hypersensitivity to rosuvastatin or any of the components of the drug.

Carefully:

For pills 10 and 20 mg

The risk of developing myopathy / rhabdomyolysis - renal failure, hypothyroidism; an indication in a personal or family history of hereditary muscular diseases, an indication of a history of muscle toxicity in the use of other HMG-CoA reductase inhibitors or fibrates; excessive drinking; conditions in which there is an increase in the plasma concentration of rosuvastatin; age over 70 years; history of liver disease; sepsis; hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine, or water-electrolyte disorders; uncontrolled epilepsy; race (mongoloid race); simultaneous reception of fibrates.

For 40 mg tablets

Renal failure of moderate severity (CC> 60 ml / min); age over 70 years; history of liver disease; sepsis; hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine, or water-electrolyte disorders; uncontrolled epilepsy.

Use during pregnancy and lactation

Rosistark^® contraindicated in 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 important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of the use of the drug in pregnant women.

If pregnancy is diagnosed during therapy, the use of the drug should be stopped immediately.

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

Application for violations of the liver

Contraindicated in liver diseases in the active phase, including a persistent increase in the activity of hepatic transaminases and any increase in the activity of transaminases in the serum of more than 3 times compared with VGN.

With caution, the drug is prescribed for indications in a history of liver disease.

Application for violations of kidney function

Contraindicated in case of moderate renal failure (CC <60 ml / min) - for 40 mg tablets,severe (CC <30 ml / min) - for pills 10 and 20 mg.

The drug should be used with caution at a dose of 40 mg in CC> 60 ml / min.

Use in children

Use of the drug is contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).

Use in elderly patients

The drug should be used with caution in patients over the age of 70 years.

special instructions

Kidney

Proteinuria, predominantly of tubular origin, was observed in patients when taking rosuvastatin in high doses, especially 40 mg, which in most cases was periodic or short-term. Such proteinuria does not mean the occurrence of acute or progressive kidney disease. The frequency of serious impairment of kidney function is increased when taking 40 mg of rosuvastatin. In such patients during treatment with Rozistark^® It is recommended to monitor indicators of renal function.

Musculoskeletal system

When using the drug Rozistark^® in all dosages, and especially when taking the drug in a dose exceeding 20 mg, myalgia, myopathy and, in rare cases, rhabdomyolysis were revealed. In very rare cases, rhabdomyolysis occurred while taking ezetimibe and HMG-CoA reductase inhibitors. In this case, the pharmacological effects of drugs cannot be excluded; therefore, these drugs should be used with caution at the same time. When taking the drug Rozistark^® at a dose of 40 mg, the incidence of rhabdomyolysis increases.

Determination of the activity of CPK

Determination of CPK activity should not be carried out after intense physical exertion or in the presence of other possible causes of increased CPK activity, which can lead to incorrect interpretation of the results. If the initial level of CPK is significantly increased (more than 5 times higher than VGN), then after 5-7 days it is necessary to re-measure. You should not start therapy if repeated measurement confirms the initial level of CPK (5 times higher compared to VGN).

Before the start of therapy

Rosistark^®, like other HMG-CoA reductase inhibitors, should be used with caution in patients with myopathy / rhabdomyolysis risk factors. These factors include:

- renal failure;

- hypothyroidism (for a dose of 40 mg);

- an indication in personal or family history of the presence of muscular diseases (for a dose of 40 mg);

- an indication of a history of myotoxicity while taking other HMG-CoA reductase inhibitors or fibrates (for a dose of 40 mg);

- alcohol abuse (for a dose of 40 mg);

- age over 70 years;

- conditions accompanied by an increase in the concentration of the drug in the blood plasma (for a dose of 40 mg);

- simultaneous administration of fibrates (for a dose of 40 mg).

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 to inform patients about the need to immediately inform the doctor about cases of sudden onset of muscle pain, muscle weakness or spasms,especially in combination with indisposition or fever. In such patients, the activity of CPK should be monitored. Treatment should be discontinued if the activity of CPK is more than 5 times higher than VGN or if the symptoms from the muscles are pronounced and cause daily discomfort, even if the activity of CPK is 5 times less than VGN. If the symptoms disappear and the activity of CPK returns to normal, consider reappointment of Rozistark^® or other HMG-CoA reductase inhibitors in smaller doses with careful monitoring of the patient. Regular monitoring of CPK activity in the absence of symptoms is not appropriate.

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 activity of CPK in the blood serum during treatment or when discontinuation of statins, including, have been observed. Rosuvastatin. Additional studies of the muscular and nervous systems, serological studies, and therapy with immunosuppressive agents may be required.

There are no signs of increased effects on skeletal muscle with rosuvastatin and concomitant therapy. However, an increase in cases of myositis and myopathy was reported in patients taking other HMG-CoA reductase inhibitors together with fibric acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid, antifungal drugs,protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when used together with some HMG-CoA reductase inhibitors. Therefore, the concomitant use of rosuvastatin and gemfibrozil is not recommended. It is necessary to carefully evaluate the ratio of risk and possible benefit when rosuvastatin is combined with fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day). The concomitant use of rozuvastatin in a dose of 40 mg and fibrates is contraindicated. 2-4 weeks after the start of treatment and / or with increasing doses of the drug Rozistark^® control of lipid metabolism indices is necessary, dose adjustment is required if necessary.

It should not be prescribed to patients with acute, severe diseases suggesting myopathy, or with possible development of secondary renal failure (for example, sepsis, arterial hypertension, surgery, trauma, metabolic syndrome, convulsions, endocrine disorders, water electrolyte disorders).

Liver

Like other HMG-CoA reductase inhibitors, Rozistark^® should be given with particular caution to patients who abuse alcohol or have a history of liver disease. It is recommended to determine the indicators of liver function before the start of therapy and 3 months after the start of therapy. If the activity of hepatic transaminases in the serum is 3 times higher than VGN, you should stop taking Rozistark^® or reduce the dose of the drug. The frequency of severity of liver dysfunction, associated mainly with increased activity of hepatic transaminases, increases when taking 40 mg of the drug.

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 among patients of Chinese and Japanese origin was detected in comparison with the figures obtained among patients of the Europeoid race.

HIV protease inhibitors

The simultaneous use of rosuvastatin with HIV protease inhibitors is not recommended.

Lactose

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

Interstitial lung disease

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

Diabetes

For 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 ability to drive motor transport and control mechanisms

Studies on 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, however, it must be borne in mind that dizziness may occur during treatment.

Overdose

Treatment: There is no specific therapy for Rosuvastatin overdose. 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.

Drug interaction

Transport protein inhibitors: Rosuvastatin binds to certain transport proteins, in particular, to OATP1B1 and DSCR. The 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 and the sections "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 in healthy volunteers. The combined use leads to an increase in the concentration of rosuvastatin in the blood plasma 11 times.The simultaneous use of drugs does not affect the concentration of cyclosporine in the blood plasma.

Vitamin K Antagonists: As with other HMG-CoA reductase inhibitors, initiation of rosuvastatin therapy or increasing the drug dose in patients receiving both indirect anticoagulants (for example, Warfarin or other coumarin anticoagulants) may lead to an increase in prothrombin time and INR. Canceling rosuvastatin or reducing the dose may cause a decrease in INR. In such cases, an INR should be monitored.

Ezetimibe: with simultaneous use of rosuvastatin and ezetimiba, no changes in AUC or C are observed_max both drugs.

Gemfibrozil and other lipid-lowering drugs: simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase in C_max and Rosuvastatin AUC. Based on data from a specific interaction study, 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 being used with HMG-CoA reductase inhibitors increased the risk of myopathy, possibly due to the fact that they can cause myopathy and when used as monotherapy. Simultaneous intake of 40 mg of rosuvastatin and fibrates is contraindicated. At the same time taking the drug with gemfibrozil and other lipid-lowering agents in a dose of more than 1 g / day, the initial dose of the drug Rozistark^® should not exceed 5 mg.

HIV protease inhibitors: Although the exact mechanism of interaction is unknown, the simultaneous administration 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 rozuvastatin and a combined preparation containing two HIV protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir) in healthy volunteers, a 2-fold increase in AUC was detected_(0-24) and 5 times C_max Rosuvastatin. Therefore, concomitant use of rosuvastatin and HIV protease inhibitors in the treatment of patients with HIV is not recommended.

Antacids: the concomitant use of rosuvastatin and suspensions of antacids containing aluminum or Magnesium hydroxide can lead to a decrease in the concentration of rosuvastatin in the blood plasma 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: taking rosuvastatin and Erythromycin at the same time may reduce AUC_(0-t) Rosuvastatin by 20% and C_max Rosuvastatin - 30%. Such an interaction may be caused by increased intestinal motility due to the use of erythromycin.

Oral contraceptives / hormone replacement therapy: the concomitant use of rosuvastatin and oral contraceptives may lead to an increase in the 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. Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy are not available, therefore, a similar effect cannot be ruled out when using this combination. However, this combination of drugs was widely used in clinical trials and was well tolerated by patients.

Isoenzymes of cytochrome P450: 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 CYP2C9 and SUR3A4 isoenzymes) and Ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes). The current use of rosuvastatin and itraconazole (an inhibitor of the isoenzyme CYP3A4) increases the AUC of rosuvastatin by 28% (clinically significant). Therefore, any interaction of drugs associated with the metabolism of cytochrome P450 is not expected.

Other medicines: no clinically significant interaction is expected with simultaneous use of rosuvastatin and Digoxin .

Drug interactions that require dose adjustment of rosuvastatin

Table 1. The effect of concomitant therapy on the exposure of rosuvastatin