Rosistarck, 20 mg 56 pcs.

Pharmacotherapeutic group: hypolipidemic drug – HMG-CoA reductase inhibitor

ATC code [C10AA07]

Pharmacological properties

Mechanism of action

Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, which is a precursor of cholesterol. The main target of rosuvastatin action is the liver, where the synthesis of cholesterol (cholesterol) and catabolism of low-density lipoproteins (LDL) are performed.
Rosuvastatin increases the number of “hepatic” LDL receptors on the surface of cells, increasing the capture and catabolism of LDL, which leads to inhibition of synthesis of very low density lipoproteins (VLDL), thus reducing the total amount of LDL and LDL.

Pharmacodynamics

. Rosuvastatin reduces elevated LDL cholesterol (LDL-C), total cholesterol and triglycerides (TG), increases concentrations of high-density lipoprotein cholesterol (HDL-C) and decreases the concentration of apolipoprotein B (ApoB), non-LDL, HDL-C, TG-LDL and increases the concentration of apolipoprotein A-I (ApoA-I), reduces the ratio of HDL-C/HC-LDL, total HC/ HC-LDL and non-HC-LDL/HC-LDL and the apoB/ApoA-I ratio.
Therapeutic effect is developed within 1 week after the therapy start and after 2 weeks of treatment it reaches 90% of the maximum possible effect.
The maximum therapeutic effect is usually reached after 4 weeks of treatment and is maintained during 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, sex or age, as well as in the treatment of patients with diabetes mellitus and hereditary form of familial hypercholesterolemia.

Rosuvatatin is effective in patients with Fredrickson type IIa and IIb hypercholesterolemia (mean baseline LDL-C concentration about 4.8 mmol/L). In 80% of such patients who received 10 mg of rosuvastatin, the concentration reaches the target values of LDL-C levels established by the European Society for the Study of Atherosclerosis – less than 3 mmol/l. In patients with heterozygous familial hypercholesteridemia who took rosuvastatin in doses from 20 to 80 mg, positive dynamics of lipid profile parameters were observed.

As a result of titration of doses up to daily dose of 40 mg (12 weeks of therapy) there was a decrease of concentration of LDL-C by 53%. In 33% of patients reached concentration of LDL-C less than 3 mmol/l, corresponding to the target standards of the European Community guidelines for atherosclerosis research.

In patients with homozygous familial hypercholesterolemia who took rosuvastatin in doses of 20 and 40 mg, the average decrease in LDL-C concentration is 22%.

In patients with hypertriglyceridemia with an initial TG concentration of 273 to 817 mg/dL who took rosuvastatin in doses of 5 mg to 40 mg once daily for six weeks, plasma TG concentrations were significantly reduced.

Additive effect is noted in combination with fenofibrate for TG content and with nicotinic acid (more than 1 g per day) for HDL-C content. In patients with low risk of coronary heart disease (CHD) (10-year Framingham scale risk less than 10%), with a mean concentration of 4.0 mmol/L (154.5 mg/dL) of LDL-C and subclinical atherosclerosis, which was assessed by thickness of “intima-media” carotid artery complex – SCIM, Rosuvastatin at a dose of 40 mg/day significantly slowed the rate of progression of maximum SCIM 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 The results of the study of statins for primary prevention showed that rosuvastatin significantly reduced the risk of cardiovascular complications with a relative risk reduction of 44%. The efficacy of therapy was noted after 6 months of using the drug. There was a statistically significant 48% reduction in the combined criterion including cardiovascular death, stroke and myocardial infarction, a 54% reduction in the incidence of fatal or non-fatal myocardial infarction and a 48% reduction in the incidence of fatal or non-fatal stroke. Overall mortality decreased by 20% in the rosuvastatin group. The safety profile in patients taking rosuvastatin at a dose of 20 mg was similar to that of the placebo group.

Pharmacokinetics

Absorption and distribution
Maximum plasma concentration of rosuvastatin is reached 5 h after oral administration. Absolute bioavailability is approximately 20%.
Rosuvastatin is metabolized primarily by 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 is bound to plasma proteins, mainly to albumin.

Metabolism
Subject to limited metabolism (about 10%). Rosuvastatin is a rather non-core substrate for metabolism by isoenzymes of cytochrome P450 system. CYP2C9 is the main isoenzyme involved in metabolism of rosuvastatin, while CYP2C19, CYP3A4 and CYP2D6 isoenzymes are less involved in 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 for inhibition of circulating HMG-CoA reductase is provided by rosuvastatin, the rest by its metabolites.

Elimation
Approximately 90% of the administered dose of rosuvastatin is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin), the remainder is excreted by the kidneys. The elimination half-life (T1/2) is approximately 19 h.
The elimination half-life does not change with increasing the drug dose. Mean geometric plasma clearance is approximately 50 l/hour (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, the membrane cholesterol transporter is involved in the hepatic uptake of rosuvatatin, which plays an important role in the hepatic elimination of rosuvastatin.

Linearity
Systemic exposure of rosuvastatin increases in proportion to dose. No changes in pharmacokinetic parameters are observed when taking the drug several times a day.

Age and sex
Gender and age have no clinically significant effect on pharmacokinetic parameters of rosuvastatin.

Ethnic groups
Comparative pharmacokinetic studies showed approximately two-fold increase in mean AUC (area under the curve “concentration – time”) and Cmax (time of reaching maximum drug concentration in plasma) in patients of Mongoloid race (Japanese, Chinese, Filipino, Vietnamese and Koreans) compared to those of Caucasoid race. In Hindus, there was an increase in the mean AUC and Cmax of approximately 1.3-fold. Pharmacokinetic analysis showed no clinically significant differences in pharmacokinetics between Caucasoid and non-Hispanic races.

Renal failure
In patients with mild to moderate renal failure, plasma concentrations of rosuvastatin or N-dismethylrosuvastatin do not change significantly. In patients with severe renal insufficiency (creatinine clearance (CK) less than 30 ml/min) the plasma concentration of rosuvastatin is 3 times higher and that of N-dismethylrosuvastatin is 9 times higher compared to healthy volunteers.
Plasma concentration of rosuvastatin in patients on hemodialysis was approximately 50% higher than in healthy volunteers.

Hepatic failure
In patients with various stages of hepatic failure with a Child-Pugh score of 7 or lower no increase in the elimination half-life of rosuvastatin was found. However, in 2 patients with Child-Pugh scores 8 and 9 there was approximately 2-fold increase of half-life. There is no experience with rosuvastatin in patients with more than a Child-Pugh score of 9.

Genetic polymorphisms
HMG-CoA reductase inhibitors, including Rosistar®, bind to the transport proteins OATP1B1 (organic anion transport polypeptide involved in statin uptake by hepatocytes) and BCRP (efflux transporter). Carriers of SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA genotypes had 1.6 and 2.4-fold increased exposure (AUC) to rosuvastatin, respectively, compared with SLCO1B1 c.521TT and ABCG2 c.421CC genotypes carriers.

Indications

Active ingredient

Composition

How to take, the dosage

If a dose of 5 mg is required, rosuvastatin may be used in other dosage form or dosage form, such as 5 mg tablets or 10 mg tablets with a ricochet (the 10 mg tablet should be divided into two parts by ricochet).

The recommended starting dose of the drug is 5 mg or 10 mg once daily both for patients who have not previously taken statins and for patients switched to this drug after therapy with other HMG-CoA reductase inhibitors. When choosing the initial dose, the cholesterol level in each individual 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, the dose may be increased after 4 weeks.

With regard to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug (see

See side effects), dose escalation to 40 mg, after an additional dose above the recommended initial dose for 4 weeks of therapy, may only be undertaken in patients with severe hypercholesterolemia and with a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia), in whom the desired therapy result was not achieved with the 20 mg dose, and who will be under medical supervision (see section “Cautionary Note”). If a dose of 40 mg is prescribed, close monitoring of the patient is recommended. It is not recommended to prescribe the 40 mg dose to patients who have not previously seen a physician.

After 2-4 weeks of therapy and/or when increasing the dose of the drug, lipid metabolism parameters should be monitored; if necessary, the dose should be adjusted.
The dose of the drug should be adjusted if it is necessary to combine it with drugs that increase the exposure to rosuvastatin.
If the exposure is expected to increase by 2 times or more, the initial dose of the drug should be 5 mg once daily. The maximum daily dose should also be adjusted so that the expected exposure to rosuvastatin does not exceed that of a 40 mg dose taken without concomitant administration of drugs that interact with rosuvastatin (see section “Interaction with other medicinal products” in Table 1).

Elderly patients
No dose adjustment is required.

Patients with renal impairment
No dose adjustment is required in patients with mild to moderate renal impairment. In patients with severe renal failure (CKD less than 30 ml/min) the drug is contraindicated. The drug in a dose of 40 mg is contraindicated in patients with moderate renal impairment (CKD 30-60 ml/min). In patients with moderate renal dysfunction, a starting dose of 5 mg of the drug is recommended.

Patients with hepatic impairment
The drug is contraindicated in patients with active liver disease (see section “Contraindications”).

Ethnic groups
Mongoloid patients may have increased systemic concentrations of rosuvastatin. This fact should be considered when prescribing the drug in these groups of patients. In administration of 10 mg and 20 mg doses the recommended initial dose for Mongoloid patients is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in these patients (see section “Contraindications”).

Genetic polymorphism
Carriers of SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA had increased exposure (AUC) to rosuvastatin compared to carriers of SLCO1B1 c.521TT and ABCG2 c.421CC genotypes. For patients who are carriers of c.521CC or c.421AA genotypes the recommended maximum dose of Rosistar® is 20 mg once daily (see sections “Pharmacokinetics” and “Precautions” and “Interaction with other medicinal products”).

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

Companion therapy
Rosuvastatin binds to various transport proteins, particularly to OATP1B1 and BCRP. When co-administering Rosistark® with drugs such as cyclosporine, certain HIV protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and/or tipranavir that increase the plasma concentration of rosuvastatin through interaction with transport proteins, the risk of myopathy including rhabdomyolysis may increase.
In such cases, the possibility of prescribing an alternative therapy or temporary discontinuation of Rosistarco® should be assessed. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with Rosistarck® should be assessed and the possibility of reducing the dose should be considered (see section “Interaction with other medicinal products”).

Interaction

The effect of the use of other drugs on rosuvastatin

Inhibitors of transport proteins: Rosuvastatin binds to some transport proteins, in particular to OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by increased plasma concentrations of rosuvastatin and an increased risk of myopathy (see Table 1 and sections “Administration and Dose” and “Precautions”).

Cyclosporine: Concomitant use of rosuvastatin and cyclosporine increased AUC of rosuvastatin 7-fold compared to values obtained in healthy volunteers (see section “Contraindications”). Concomitant use leads to an 11-fold increase in plasma concentrations of rosuvastatin. Concomitant use of the drugs has no effect on the plasma concentration of cyclosporine.

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

Gemfibrozil and other hypolipidemic agents: Concomitant use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax and AUC of rosuvastatin (see section “Special indications”). Based on the data of the study of specific interactions, no pharmacokinetic interaction with fenofibrate is expected, but pharmacodynamic interaction is possible. Hemfibrozil, fenofibrate, other fibrates and nicotinic acid at lipid-lowering doses (1 g or more per day) when used simultaneously with HMG-CoA reductase inhibitors increased the risk of myopathy, possibly due to the fact that they can also cause myopathy when used as monotherapy. Simultaneous use of 40 mg of rosuvastatin and fibrates is contraindicated (see section “Special Precautions” and “Contraindications”). When concomitant use of the drug with gemfibrozil and other lipid-lowering drugs at a dose greater than 1 g/day the starting dose of Rosistar® should not exceed 5 mg.

HIV protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant administration of rosuvastatin with HIV protease inhibitors may result in a significant increase in rosuvastatin exposure. In a pharmacokinetic study, concomitant administration of 20 mg of rosuvastatin and a combination drug containing two HIV protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers showed a 2-fold increase in AUC(0-24) and 5-fold increase in Cmax of rosuvastatin. Therefore, concomitant administration of rosuvastatin and HIV protease inhibitors in patients with HIV is not recommended.

Antacids: Concomitant administration of rosuvastatin and suspensions of antacids containing aluminum or magnesium hydroxide may lead to a decrease in plasma concentrations of rosuvastatin by about 50%. This effect is weaker if antacids are used 2 h after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Eritromycin: Concomitant administration of rosuvastatin and erythromycin may decrease AUC(0-t) of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction may be due to increased intestinal motility caused by taking 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 rather weak substrate for these isoenzymes. No clinically significant interaction between rosuvastatin and fluconazole (inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (inhibitor of CYP2A6 and CYP3A4 isoenzymes) was found. Current use of rosuvastatin and itraconazole (CYP3A4 isoenzyme inhibitor) increases the AUC of rosuvastatin by 28% (clinically significant). Therefore, no drug interaction related to cytochrome P450 metabolism is expected.

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

The effect of using rosuvastatin on other drugs

Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, starting therapy with rosuvastatin or increasing the dose of the drug in patients receiving indirect anticoagulants (such as warfarin or other coumarin anticoagulants) simultaneously may increase prothrombin time (international normalized ratio – INR). Discontinuation of rosuvastatin or reduction of the dose may cause a decrease in INR. INR should be monitored in such cases.

Peroral contraceptives/ hormone replacement therapy:
concomitant administration of rosuvastatin and oral contraceptives may increase AUC of ethinylestradiol and norgestrel by 26 % and 34 %, respectively. This 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 when using this combination cannot be excluded. However, this combination of drugs has been widely used in clinical trials and was well tolerated by patients.

Other medicinal products: No clinically significant interaction is expected with the simultaneous use of rosuvastatin and digoxin.

Drug interactions that require dose adjustments of rosuvastatin (see Table 1).

The dose of Rosistar® should be adjusted if co-administration with drugs that increase exposure to rosuvastatin is necessary. If exposure is expected to increase by a factor of 2 or more, the starting dose of Rosistar® should be 5 mg once daily. The maximum daily dose of Rosistarck® should also be adjusted so that the expected exposure to rosuvastatin does not exceed that of a 40 mg dose taken without concomitant administration of drugs that interact with rosuvastatin. For example, maximum daily dose of Rosistarque® in concomitant use with gemfibrozil is 20 mg (1.9-fold increase of exposure), with ritonavir/atazanavir – 10 mg (3.1-fold increase of exposure).

Table 1.
Effect of concomitant therapy on exposure to rosuvastatin (AUC, data are given in descending order) – results of published clinical trials.

Renal effects
Proteinuria, predominantly of tubular origin, has been noted in patients taking high doses of rosuvastatin, particularly 40 mg, which has been intermittent or transient in most cases. Such proteinuria does not indicate the occurrence of acute or progressive renal disease. The incidence of serious renal dysfunction is increased when taking 40 mg rosuvastatin. In these patients it is recommended to monitor renal function parameters during treatment with Rosistarcoe®.

Motor system disorders
Myalgia, myopathy and, in rare cases, rhabdomyolysis have been observed with Rosistarca® at all doses, and particularly with doses greater than 20 mg.

Creatine phosphokinase (CPK)
Measurement of CPK activity should not be performed after vigorous exercise or if other possible causes of increased CPK activity are present, which may lead to misinterpretation of results. If the baseline level of CPK is significantly elevated (more than 5 times the upper limit of normal), the measurement should be repeated in 5-7 days. The therapy should not be started if the repeat measurement confirms the initial CPK level (5 times higher than the upper limit of normal).

Pre-therapy
Rosistarco®, like other HMG-CoA reductase inhibitors, should be prescribed with caution in patients with existing risk factors for myopathy/rhabdomyolysis (see section “Caution”). The risk/benefit ratio of therapy should be evaluated and clinical monitoring should be performed throughout the course of treatment.

In therapy
Patients should be advised to promptly inform their physician if they experience sudden onset of muscle pain, muscle weakness or cramps, especially if associated with malaise or fever. In such patients, monitoring of CPK activity should always be performed. Treatment should be discontinued if CPK activity is more than 5 times the upper limit of normal or if muscle symptoms are severe and cause daily discomfort, even if CPK activity is 5 times less than the upper limit of normal. If symptoms disappear and CPK activity returns to normal, the re-prescription of Rosistarco® or other HMG-CoA reductase inhibitors at lower doses should be considered with close monitoring of the patient. Regular monitoring of CPK activity in the absence of symptoms is unnecessary.

There have been very rare cases of immune-mediated necrotizing myopathy with clinical manifestations as persistent proximal muscle weakness and elevated serum CPK levels during treatment or upon discontinuation of statins, including rosuvastatin. Additional muscular and nervous system studies, serologic studies, and therapy with immunosuppressive agents may be necessary.

There have been no indications of increased skeletal muscle effects 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 fibrin acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid, antifungal drugs, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when coadministered with some HMG-CoA reductase inhibitors. Therefore, concomitant administration of rosuvastatin and gemfibrozil is not recommended. The risk/benefit ratio of co-administration of rosuvastatin with fibrates or nicotinic acid at lipid-lowering doses (more than 1 g/day) should be carefully evaluated. Concomitant administration of 40 mg rosuvastatin and fibrates is contraindicated (see sections “Interaction with other medicinal products” and “Side effects”).

Two to four weeks after the start of treatment and/or if the dose of Rosistarck® is increased, the lipid metabolism parameters should be monitored; if necessary, the dose should be adjusted.

Liver
Like other HMG-CoA reductase inhibitors, Rosistarck® should be prescribed with special caution in patients who abuse alcohol or have a history of liver disease. It is recommended that liver function tests be performed before and 3 months after the start of therapy. If serum hepatic transaminase activity exceeds 3 times the upper limit of normal, discontinue Rosistarco® or decrease the drug dose (see section “Dosage and administration”). In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome therapy of the underlying disease should be carried out before treatment with rosuvastatin.

Ethnic groups
Pharmacokinetic studies have shown increased systemic concentrations of rosuvastatin in patients of Chinese and Japanese origin compared to those in patients of Caucasian race (see section “Administration and Doses” and “Pharmacokinetics”).

HIV protease inhibitors
Concurrent use of rosuvastatin with HIV protease inhibitors is not recommended (see section “Interaction with other medicinal products”).

Lactose
Do not use the drug in patients with lactase deficiency, galactose intolerance and glucose-galactose malabsorption.

Interstitial lung disease
Single cases of interstitial lung disease have been reported with some statins, especially for long periods of time. Manifestations of the disease may include dyspnea, dry cough, and worsening of general well-being (weakness, weight loss, and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

Type 2 diabetes
For patients with glucose concentrations between 5.6 and 6.9 mmol/L, use of rosuvastatin leads to an increased risk of developing type 2 diabetes.

Influence on the ability to drive vehicles and mechanisms

There have been no studies on the effect of rosuvastatin on the ability to drive vehicles and mechanisms. Based on the pharmacodynamic properties of the drug it can be assumed that rosuvastatin should not have this effect, however, it should be taken into account that dizziness may occur during treatment.

Contraindications

Risk of myopathy/rhabdomyolysis – renal failure, hypothyroidism; personal or family history of hereditary muscle disease and prior history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; conditions in which increased plasma concentrations of rosuvastatin have been noted; age over 70 years; history of liver disease; sepsis; arterial hypotension; major surgical interventions; trauma; severe metabolic, endocrine or water-electrolyte disorders; uncontrolled epilepsy; race (mongoloid race); concomitant use of fibrates; concomitant use with colchicine and ezetimibe.

Side effects

Skin disorders:
infrequent: skin itching, rash, urticaria;
unspecified frequency: Stevens-Johnson syndrome.

Gastrointestinal tract:
common: constipation, nausea, abdominal pain;
rare: pancreatitis;
very rare: jaundice, hepatitis;
unspecified frequency: diarrhea.

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

Immune system disorders:
rare: hypersensitivity, including angioedema.

Endocrine system disorders:
often: diabetes mellitus type 2.

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

Musculoskeletal system:
frequent: myalgia;
rare: myopathy (including myositis), rhabdomyolysis;
very rare: arthralgia;
unspecified frequency: immune-mediated necrotizing myopathy.
Skeletal muscle effects causing myalgia, myopathy (including myositis) and, rarely, rhabdomyolysis with or without acute renal failure have been observed in patients taking any dose of rosuvastatin, especially when taking doses greater than 20 mg. A dose-dependent increase in creatine phosphokinase (CPK) activity was detected in patients taking rosuvastatin, but in most cases these manifestations were insignificant, asymptomatic and temporary. In case of an increase of CPK activity more than 5 times the upper limit of normal, therapy should be suspended (see section “Special Precautions”).

Uses of the urinary system
Proteinuria may be observed when taking rosuvastatin. Changes in protein content in urine (from the absence or presence of trace amounts to levels ++ and higher) are observed in less than 1% of patients taking rosuvastatin in doses of 10 mg and 20 mg and in about 3% of patients taking the drug in dose of 40 mg. A slight change in the amount of protein in the urine, expressed as a change from zero or trace levels to a + level, was observed when taking the drug at a dose of 20 mg. In most cases, proteinuria decreased and passed on its own during treatment. When analyzing the data of clinical studies no causal relationship between proteinuria and acute or progressive kidney disease was found.
Very rare: hematuria, microhematuria.

Hepatic disorders
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 parameters
The following changes in laboratory parameters have been observed during use of rosuvastatin: increased concentration of glucose, bilirubin, activity of gamma-glutamyl transpeptidase, alkaline phosphatase, thyroid function disorders.

Hematopoietic system disorders:
unspecified frequency: thrombocytopenia.

Respiratory system disorders:
unspecified frequency: cough, shortness of breath.

Reproductive and mammary system disorders:
unspecified frequency: gynecomastia.

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

In long-term use of rosuvastatin, single cases of interstitial lung disease have been reported.

Overdose

Pregnancy use

Similarities