Rozistark pills 10mg №28

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 Rosuvastatin is the liver, where cholesterol (cholesterol) synthesis and LDL catabolism are performed.
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 elevated levels of cholesterol-cholesterol, total cholesterol and triglycerides (TG), increases the concentration of cholesterol-HDL cholesterol, decreases the concentration of apolipoprotein B (ApoB), cholesterol-LPVP, cholesterol-VLDLP, TG-VLPA and increases the concentration of apolipoprotein A (ApoA-I), reduces the ratio of XC-LDL / XC-HDL, total XC / XC-HDL and HS-non-LPVP / XC-HDL and the ratio ApoV / ApoA-I.
The therapeutic effect develops within one week after the start of therapy with the drug, after 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved after 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 their race, gender, or age, as well as in treating patients with diabetes and the hereditary form of familial hypercholesterolemia.
Rosuvastatin is effective in patients with hypercholesterolemia IIa and IIb type according to Fredrickson (the average initial concentration of LDL-C is about 4.8 mmol / l). In 80% of these patients who received 10 mg of rosuvastatin, the concentration reaches the target values ​​of cholesterol-LDL levels established by the European Community for the study of atherosclerosis - less than 3 mmol / l. Patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses of 20 to 80 mg show a positive trend in lipid profile parameters.
As a result of titration of doses up 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, the concentration of cholesterol-LDL is less than 3 mmol / l, which corresponds to the target standards of the European atherosclerosis research guidelines.
In patients with homozygous familial hypercholesterolemia who took rosuvastatin at doses of 20 and 40 mg, the average decrease in the concentration of LDL-C is 22%. In patients with hypertriglyceridemia with an initial TG concentration of 273 to 817 mg / dL, who took rosuvastatin at a dose of 5 mg to 40 mg once a day for 6 weeks, the concentration of TG in the blood plasma significantly decreased.
An additive effect is observed in combination with fenofibrate in relation to the TG content and with nicotinic acid (more than 1 g per day) in relation to the content of HDL-C. In patients with a low risk of developing coronary heart disease (10-year risk on the Framingham scale - less than 10%), with an average concentration of LDL-C of 4 mmol / l (154.5 mg / dL) and subclinical atherosclerosis, which was assessed by the thickness of the intima complex -media "carotid arteries (TCIM), rosuvastatin at a dose of 40 mg / day significantly slowed the rate of progression of the maximum TCIM for 12 carotid artery segments compared with placebo with a difference of 0.0145 mm / year (95% confidence interval (CI)): 0,0196 to? 0,0093; p <0,001).
The study was conducted in patients with a low risk of coronary artery disease, for which a dose of 40 mg is not recommended. The dose of 40 mg should be prescribed only to patients with severe hypercholesterolemia and a high risk of cardiovascular diseases.
The results of a study on the use of statins for primary prophylaxis showed that rosuvastatin significantly reduced the risk of cardiovascular complications with a relative risk reduction of 44%.
The effectiveness of therapy was noted after 6 months of use of the drug. There was a statistically significant reduction of 48% of the combined criterion, including death from cardiovascular diseases, stroke and myocardial infarction, a 54% reduction in the occurrence of fatal or nonfatal myocardial infarction and 48% in fatal or nonfatal stroke. Total mortality decreased by 20% in the rosuvastatin group. The safety profile of patients taking rosuvastatin at a dose of 20 mg was similar to that of the placebo group.

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 (eg, exercise, 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).

Dosing regimen:
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 do not require dose adjustment.
In patients with mild to moderate renal insufficiency, dose adjustment is not required. In patients with severe renal failure (CC <30 ml / min), the use of the drug is contraindicated. Patients with moderate renal impairment are recommended an initial dose of 5 mg. 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 in patients with liver disease in the active phase.
In Mongoloid patients, 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 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 initial dose for patients with a predisposition to myopathy is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.

Side effect:
The side effects associated with taking Rosistark® are usually moderately severe and disappear 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.
From the hematopoietic system: unspecified frequency - thrombocytopenia.
On the part of the digestive system: often - constipation, nausea, abdominal pain; rarely - pancreatitis.
On the part of the liver: when rosuvastatin is used, there is a dose-dependent increase in the activity of hepatic transaminases in a small number of patients. In most cases, this increase is insignificant, asymptomatic and temporary.
On the part of the endocrine system: often - diabetes mellitus type 2, dysfunction of the thyroid gland.
From the musculoskeletal system: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis; unspecified frequency - immune-mediated necrotizing myopathy.
Effects on skeletal muscles causing 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 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.
On the part of the urinary system: when receiving rosuvastatin can be observed proteinuria. 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.

On the part of the skin: infrequently - itching, rash, hives.
Reproductive system and mammary glands: unspecified frequency - gynecomastia.
Laboratory indicators: increase in the concentration of glucose, bilirubin, activity of GGT, ALP.
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 use:
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 (efficiency 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 (efficiency 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; states thatat which increase in plasma concentration of rozuvastatin is noted; 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® 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 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 renal 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 Rosistark®, it is recommended to monitor renal function indicators.
Musculoskeletal system
At use of the drug Rosistark® in all dosages, and, in particular at administration of drug in a dose exceeding 20 mg, the myalgia, a myopathy and, in rare instances, a rhabdomyolysis has come to light. 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 Rosistark® at a dose of 40 mg, the frequency of cases 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 report to 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, consideration should be given to 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 myositis and myopathy has been 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 an increase in the dose of Rosistark®, monitoring of lipid metabolism indices is necessary, and if necessary, dose adjustment is required.
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, Rosistark® should be used with extreme caution in 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 Rosistark® 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 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.

Drug Interactions:
Transport protein inhibitors: Rosuvastatin binds to certain transport proteins, in particular, OATP1B1 and DSCR. 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 sections "Mode of application and doses and special instructions).
Cyclosporine: with the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin increased by 7 times compared with values ​​obtained from 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, initiating rosuvastatin therapy or increasing the drug dose in patients who receive both indirect anticoagulants (for example, Warfarin or other coumarin anticoagulants) can 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 the simultaneous use of rosuvastatin and ezetimibe, there is no change in the AUC or Cmax of both drugs.
Gemfibrozil and other hypolipidemic agents: the simultaneous use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax and AUC of rosuvastatin. 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 Rosistark® should not exceed 5 mg.
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 rozuvastatin and a combined preparation containing two HIV protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir), healthy volunteers showed a 2-fold increase in AUC (0-24) and 5 times Cmax of 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 about 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 : the concomitant use of rosuvastatin and erythromycin can lead to a decrease in AUC (0-t) of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. Such an interaction may be caused by increased intestinal motility due to the use of erythromycin.
Oral contraceptives / hormone replacement therapy: co-administration 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. 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.
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 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 drugs: no clinically significant interaction is expected with simultaneous use of rosuvastatin and Digoxin .

Storage conditions:
The drug should be stored out of the reach of children at a temperature not higher than 25 ° C.