Instructions for Rosister tablets 10 mg No. 30
Composition
active ingredient: rosuvastatin;
1 tablet contains 10 mg of rosuvastatin;
excipients: lactose monohydrate; microcrystalline cellulose; crospovidone; calcium phosphate; magnesium stearate;
shell: Opadry II Pink film coating mixture: hypromellose (hydroxypropylmethylcellulose); lactose monohydrate; titanium dioxide (E 171); triacetin; iron oxide red (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets with a biconvex surface, coated with a pink film coating.
Pharmacotherapeutic group
Lipid-lowering agents. HMG-CoA reductase inhibitors.
ATX code C10A A07.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of cholesterol. The primary site of action of rosuvastatin is the liver, a target organ for lowering cholesterol levels.
Rosuvastatin increases the number of low-density lipoprotein (LDL) receptors on the surface of liver cells, enhancing the uptake and catabolism of LDL, and inhibits the hepatic synthesis of very low-density lipoprotein (VLDL), thereby reducing the total number of VLDL and LDL particles.
Pharmacodynamic action
Rosuvastatin reduces elevated LDL-cholesterol (LDL-C), total cholesterol, and triglycerides (TG), and increases high-density lipoprotein cholesterol (HDL-C). It also reduces apolipoprotein B (ApoB), non-LDL-C, VLDL-C, TG-VLDL, and increases apolipoprotein ApoA-I. Rosuvastatin also reduces the LDL-C/HDL-C ratio, total cholesterol/HDL-C, non-LDL-C/HDL-C, and apoB/apoA-I ratios.
The therapeutic effect is achieved within 1 week after the start of the drug, 90% of the maximum effect is achieved after 2 weeks. The maximum effect is usually achieved after 4 weeks and continues thereafter.
Clinical efficacy
Rosuvastatin is effective in the treatment of adults with hypercholesterolemia - with or without hypertriglyceridemia - regardless of race, sex, or age, as well as patients in special groups such as diabetics or patients with familial hypercholesterolemia.
It has been reported that approximately 80% of patients with type IIa and IIb hypercholesterolemia (mean baseline LDL-C level approximately 4.8 mmol/L) receiving rosuvastatin at a dose of 10 mg were able to achieve normative target LDL-C levels.
It is known that in a study of patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses from 20 to 80 mg according to the scheme of increased dose titration, the drug had a beneficial effect on lipid parameters and achieved target levels at all doses. After titration to a daily dose of 40 mg (12 weeks of treatment), LDL-C decreased by 53%. In 33% of patients, normal LDL-C levels (< 3 mmol/L) were achieved.
It is known that in a dose-titration study, the response to rosuvastatin at doses of 20-40 mg mg was studied in patients with homozygous familial hypercholesterolemia. In the general population, LDL-C levels decreased by an average of 22%.
It is known that in clinical studies involving a limited number of patients, an additive effect of rosuvastatin on reducing triglyceride levels when used in combination with fenofibrate and on increasing HDL-C levels when used in combination with niacin was observed (see section "Special instructions").
In patients aged 45-70 years with a low risk of coronary heart disease (defined as a Framingham risk score < 10% over 10 years), a mean LDL-C of 4.0 mmol/L (154.5 mg/dL), but with subclinical atherosclerosis (defined as increased carotid intima-media thickness – CIMST) who took rosuvastatin 40 mg once daily for 2 years, there was a significant slowdown in the progression of maximum CIMST at 12 carotid artery sites compared to placebo.
A direct correlation between a decrease in TCIMSA and a decrease in the risk of cardiovascular disorders has not been demonstrated. This study included patients with low risk of ischemic heart disease, who are not representatives of the target population for the use of rosuvastatin at a dose of 40 mg. The 40 mg dose should be prescribed only to patients with severe hypercholesterolemia and a high risk of cardiovascular disorders (see section "Method of administration and dosage").
It is known that the use of rosuvastatin as a means of primary prevention of major atherosclerotic cardiovascular diseases at a dose of 20 mg once daily for 2 years in men (≥ 50 years) and women (≥ 60 years) resulted in a decrease in LDL-cholesterol concentrations compared to placebo.
It has been reported that in patients aged 10-17 years (Tanner stage II-V girls who had started menstruating at least 1 year previously) with heterozygous familial hypercholesterolemia who received rosuvastatin 5, 10, or 20 mg/day for 12 weeks followed by a 40-week open-label dose titration period with rosuvastatin, LDL-C levels decreased by 38.3%, 44.6%, and 50%, respectively, in the rosuvastatin 5, 10, and 20 mg groups compared with 0.7% in the placebo group. At the end of the 40-week open-label dose titration period to reach the target level (maximum dose was 20 mg once daily), 40.5% of patients achieved the target LDL-C level of less than 2.8 mmol/L. After 52 weeks of study treatment, no effect on height, weight, body mass index (BMI) or puberty was observed (see section 4.4). Experience in children and adolescents is limited and the long-term effects of rosuvastatin (>1 year) on puberty are unknown.
Pharmacokinetics
Absorption: Peak plasma concentrations of rosuvastatin are reached approximately 5 hours after oral administration. Absolute bioavailability is approximately 20%.
Distribution: Rosuvastatin is extensively taken up by the liver, which is the main site of cholesterol synthesis and LDL-C clearance. The volume of distribution of rosuvastatin is approximately 134 L. About 90% of rosuvastatin is bound to plasma proteins, mainly albumin.
Metabolism. Rosuvastatin undergoes minor metabolism (approximately 10%). In vitro metabolism studies using human hepatocytes indicate that rosuvastatin is a poor substrate for metabolism by cytochrome P450 enzymes. The main isoenzyme involved is CYP2C9, with 2C19, 3A4 and 2D6 playing a somewhat smaller role. The main identified metabolites are the N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximately 50% less active than rosuvastatin, the lactone metabolite is considered clinically inactive. Rosuvastatin accounts for more than 90% of the circulating HMG-CoA reductase inhibitory activity.
Excretion. Approximately 90% of the rosuvastatin dose is excreted unchanged in the feces (absorbed and unabsorbed active substance together), the rest is excreted in the urine. Approximately 5% is excreted in the urine in unchanged form. The half-life from blood plasma is approximately 19 hours and does not increase with increasing dose. The geometric mean value of the drug clearance from blood plasma is approximately 50 l/h (coefficient of variation - 21.7%). As for other HMG-CoA reductase inhibitors, hepatic uptake of rosuvastatin occurs with the participation of the membrane transporter OATP-C, which plays an important role in the hepatic elimination of rosuvastatin.
Linearity. Systemic exposure to rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with repeated daily administration.
Special patient groups
Age and gender: There was no clinically significant effect of age or gender on the pharmacokinetics of rosuvastatin in adults. The pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolemia were similar to those in adult volunteers (see section "Children").
Race: Pharmacokinetic studies have shown that in patients of Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) the median AUC and Cmax values are approximately twice as high as in Caucasians; in Indians the median AUC and Cmax values are increased by approximately 1.3 times. Population pharmacokinetic analysis has not revealed any clinically significant differences between Caucasian and Negroid patients.
Renal impairment. In patients with varying degrees of renal impairment, no changes in plasma concentrations of rosuvastatin or the N-desmethyl metabolite were observed in subjects with mild or moderate renal impairment. In patients with severe renal impairment (creatinine clearance < 30 ml/min), plasma concentrations of rosuvastatin were 3 times higher, and those of the N-desmethyl metabolite were 9 times higher, than in healthy volunteers. Steady-state plasma concentrations of rosuvastatin in patients on hemodialysis were approximately 50% higher than in healthy volunteers.
Hepatic impairment. In patients with varying degrees of hepatic impairment, no evidence of increased exposure to rosuvastatin was observed in patients with Child-Pugh scores of 7 or less. However, in two patients with Child-Pugh scores of 8 and 9, systemic exposure was at least twice as high as in patients with lower scores. There is no experience with rosuvastatin in patients with Child-Pugh scores greater than 9.
Genetic polymorphism. The distribution of HMG-CoA reductase inhibitors, including rosuvastatin, occurs with the participation of transport proteins OATP1B1 and BCRP. Patients with genetic polymorphisms of SLCO1B1 (OATP1B1) and/or ABCG2 (BCRP) are at risk of increased exposure to rosuvastatin. With certain forms of the SLCO1B1 p.521CC and ABCG2 p.421AA polymorphisms, rosuvastatin exposure (AUC) is increased compared with the SLCO1B1 p.521TT or ABCG2 p.421CC genotypes. Specific genotyping is not provided in clinical practice, but patients with such polymorphisms are recommended to use a lower daily dose of rosuvastatin.
Pharmacokinetic parameters in children with heterozygous familial hypercholesterolemia aged 10 to 17 years have not been fully determined. A small pharmacokinetic study of rosuvastatin (tablet form) in pediatric patients showed that the drug exposure in children is similar to that in adults. The results also indicate that no significant dose-proportional deviations are expected.
Indication
Treatment of hypercholesterolemia
Adults, adolescents and children aged 10 years and over with primary hypercholesterolemia (type IIa, including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (type IIb) as an adjunct to diet when diet and other non-pharmacological measures (e.g. exercise, weight loss) are inadequate.
In homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering treatments (e.g. LDL apheresis) or in cases where such treatment is inappropriate.
Prevention of cardiovascular disorders
Prevention of major cardiovascular events in patients estimated to be at high risk of a first cardiovascular event, as an adjunct to correction of other risk factors.
Contraindication
The drug Rosister® is contraindicated:
patients with hypersensitivity to rosuvastatin or to any of the excipients of the drug; patients with active liver disease, including persistent elevations of serum transaminases of unknown etiology and any elevations of serum transaminases exceeding three times the upper limit of normal (ULN); patients with severe renal impairment (creatinine clearance < 30 ml/min); patients with myopathy; patients receiving concomitant cyclosporine; pregnancy or breastfeeding, as well as women of childbearing potential not using adequate contraception.
The 40 mg dose is contraindicated in patients with a predisposition to myopathy/rhabdomyolysis.
Such risk factors include:
moderate renal impairment (creatinine clearance < 60 ml/min); hypothyroidism; personal or family history of hereditary muscle diseases; history of myotoxicity with other HMG-CoA reductase inhibitors or fibrates; alcohol abuse; situations that may lead to increased plasma drug concentrations; Mongoloid race;
concomitant use of fibrates (see sections "Pharmacokinetics", "Interaction with other medicinal products and other types of interactions" and "Special precautions for use").
Interaction with other medicinal products and other types of interactions
Effect of concomitant medications on rosuvastatin
Transporter protein inhibitors: Rosuvastatin is a substrate for several transporter proteins, including the hepatic uptake transporter OATP1B1 and the efflux transporter BCRP. Concomitant use of rosuvastatin with medicinal products that inhibit these transporters may result in increased plasma concentrations of rosuvastatin and an increased risk of myopathy (see sections 4.4 and 4.2).
Cyclosporine: During concomitant use of rosuvastatin and cyclosporine, rosuvastatin AUC values were on average approximately 7 times higher than those observed in healthy volunteers (see table). Rosuvastatin is contraindicated in patients receiving concomitant cyclosporine (see section "Contraindications").
Concomitant use did not affect the plasma concentrations of cyclosporine.
Protease inhibitors. Although the exact mechanism of interaction is unknown, concomitant use of protease inhibitors may significantly increase rosuvastatin exposure (see table). It is known that in a pharmacological study, co-administration of 10 mg of rosuvastatin and a combination product containing two protease inhibitors (300 mg atazanavir/100 mg ritonavir) in healthy volunteers was accompanied by an increase in AUC and Cmax of rosuvastatin by approximately 3 and 7 times, respectively. The simultaneous use of rosuvastatin and some combinations of protease inhibitors is possible after careful consideration of the dose adjustment of rosuvastatin, taking into account the expected increase in rosuvastatin exposure (see sections “Method of administration and dosage”, “Special instructions for use”).
Gemfibrozil and other lipid-lowering agents: Concomitant use of rosuvastatin and gemfibrozil resulted in a 2-fold increase in rosuvastatin AUC and Cmax (see section 4.4).
Ezetimibe. Co-administration of rosuvastatin 10 mg and ezetimibe 10 mg in patients with hypercholesterolemia resulted in a 1.2-fold increase in rosuvastatin AUC. A pharmacodynamic interaction between rosuvastatin and ezetimibe, which could lead to adverse events, cannot be excluded (see section 4.4).
Antacids. Concomitant administration of rosuvastatin with antacid suspensions containing aluminum or magnesium hydroxide reduced rosuvastatin plasma concentrations by approximately 50%. This effect was less pronounced when antacids were administered 2 hours after rosuvastatin. The clinical significance of this interaction has not been studied.
Erythromycin: Concomitant use of rosuvastatin and erythromycin decreased rosuvastatin AUC by 20% and Cmax by 30%. This interaction may be due to increased intestinal motility due to erythromycin.
Cytochrome P450 enzymes. In vitro and in vivo studies have shown that rosuvastatin does not inhibit or induce cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, drug interactions resulting from P450-mediated metabolism are not expected. No clinically significant interactions were observed between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4).
Interactions requiring dose adjustment of rosuvastatin
If it is necessary to use rosuvastatin with other drugs that can increase its exposure, the dose of rosuvastatin should be adjusted. If the exposure of the drug (AUC) is expected to increase by approximately 2 or more times, the use of rosuvastatin should be started at a dose of 5 mg once a day. The maximum daily dose of rosuvastatin should be adjusted so that the expected exposure of rosuvastatin does not exceed the exposure observed when taking a dose of 40 mg per day without the use of drugs that interact with the drug; for example, when used with gemfibrozil, the dose of rosuvastatin will be 20 mg (an increase in exposure of 1.9 times), when used with the combination of ritonavir/atazanavir - 10 mg (an increase of 3.1 times).
Effect of concomitant medications on rosuvastatin exposure (AUC; in decreasing order of magnitude)
| Dosing regimen of the interacting drug | Rosuvastatin dosage regimen | Changes in rosuvastatin AUC* |
| Cyclosporine 75 mg twice daily to 200 mg twice daily, 6 months | 10 mg once daily, 10 days | ↑ 7.1 times |
| Regorafenib 160 mg once daily, 14 days | 5 mg, single dose | ↑ 3.8 times |
| Atazanavir 300 mg/ritonavir 100 mg once daily, 8 days | 10 mg, single dose | ↑ 3.1 times |
| Velpatasvir 100 mg once daily | 10 mg, single dose | ↑ 2.7 times |
| Ombitasvir 25 mg/paritaprevir 150 mg/ritonavir 100 mg once daily/dasabuvir 400 mg twice daily, 14 days | 5 mg, single dose | ↑ 2.6 times |
| Grazoprevir 200 mg/elbasvir 50 mg once daily, 11 days | 10 mg, single dose | ↑ 2.3 times |
| Glecaprevir 400 mg/pibrentasvir 120 mg once daily, 7 days | 5 mg once daily, 7 days | ↑ 2.2 times |
| Lopinavir 400 mg/ritonavir 100 mg twice daily, 17 days | 20 mg once daily, 7 days | ↑ 2.1 times |
| Clopidogrel 300 mg, then 75 mg 24 hours later | 20 mg, single dose | ↑ 2 times |
| Gemfibrozil 600 mg twice daily, 7 days | 80 mg, single dose | ↑ 1.9 times |
| Eltrombopac 75 mg once daily, 5 days | 10 mg, single dose | ↑ 1.6 times |
| Darunavir 600 mg/ritonavir 100 mg twice daily, 7 days | 10 mg once daily, 7 days | ↑ 1.5 times |
| Tipranavir 500 mg/ritonavir 200 mg twice daily, 11 days | 10 mg, single dose | ↑ 1.4 times |
| Dronedarone 400 mg twice daily | Unknown | ↑ 1.4 times |
| Ezetimibe 10 mg once daily, 14 days | 10 mg once daily, 14 days | ↑ 1.2 times ** |
| Fosamprenavir 700 mg/ritonavir 100 mg twice daily, 8 days | 10 mg, single dose | ↔ |
| Aleglitazar 0.3 mg, 7 days | 40 mg, 7 days | ↔ |
| Silymarin 140 mg 3 times a day, 5 days | 10 mg, single dose | ↔ |
| Fenofibrate 67 mg 3 times a day, 7 days | 10 mg, 7 days | ↔ |
| Rifampin 450 mg once daily, 7 days | 20 mg, single dose | ↔ |
| Ketoconazole 200 mg twice daily, 7 days | 80 mg, single dose | ↔ |
| Fluconazole 200 mg once daily, 11 days | 80 mg, single dose | ↔ |
| Erythromycin 500 mg 4 times a day, 7 days | 80 mg, single dose | ↓ 20% |
| Baicalin 50 mg 3 times a day, 14 days | 20 mg, single dose | ↓ 47% |
* - Data presented as x-fold change represents the ratio between rosuvastatin in combination and alone. Data presented as % change represents the % difference relative to rosuvastatin alone.
Increase is indicated by ↑, no change by ↔, decrease by ↓.
** - From interaction studies at different doses of rosuvastatin, the table shows the most significant ratio.
Vitamin K antagonists. As with other HMG-CoA reductase inhibitors, when initiating or increasing the dose of rosuvastatin in patients receiving concomitant vitamin K antagonists (e.g. warfarin or another coumarin anticoagulant), an increase in the international normalized ratio (INR) may occur. Discontinuation of rosuvastatin or dose reduction may result in a decrease in INR. In such cases, appropriate monitoring of INR is advisable.
Oral contraceptives/hormone replacement therapy (HRT). Concomitant use of rosuvastatin and oral contraceptives resulted in an increase in the AUC of ethinylestradiol and norgestrel by 26% and 34%, respectively. This increase in plasma levels should be taken into account when selecting the dose of oral contraceptives. There are no data on the pharmacokinetics of drugs in patients taking rosuvastatin and HRT simultaneously, so a similar effect cannot be excluded. However, the combination has been widely used in women and is well tolerated.
Other medicines
Digoxin: Based on specific interaction studies, no clinically significant interaction with digoxin is expected.
Fusidic acid. Interaction studies with rosuvastatin and fusidic acid have not been conducted. The risk of myopathy, including rhabdomyolysis, may be increased by concomitant use of systemic fusidic acid with statins. The mechanism of this interaction (pharmacodynamic or pharmacokinetic, or both) is not yet understood. Rhabdomyolysis (including some fatal cases) has been reported in patients receiving this combination.
In patients in whom the use of systemic fusidic acid is considered necessary, treatment with Rosistero® should be discontinued for the entire duration of fusidic acid treatment.
Children
Interaction studies have only been conducted in adults. The extent of interaction in children is unknown.
Application features
Effects on the kidneys
It is known that cases of proteinuria (determined by the "dipstick test"), mainly tubular in origin and in most cases transient or intermittent, have been observed in patients taking rosuvastatin at high doses, in particular 40 mg. Proteinuria was not a harbinger of acute or progressive renal disease. Renal adverse events were observed more often with the 40 mg dose. In patients taking rosuvastatin at a dose of 40 mg, renal function should be checked regularly.
Effects on skeletal muscles
Skeletal muscle disorders, such as myalgia, myopathy and, rarely, rhabdomyolysis, have been reported in patients taking rosuvastatin at all doses, particularly above 20 mg. Very rare cases of rhabdomyolysis have been reported when ezetimibe was used in combination with HMG-CoA reductase inhibitors. The possibility of a pharmacodynamic interaction cannot be excluded (see section 4.5), and therefore this combination should be used with caution.
As with other HMG-CoA reductase inhibitors, the incidence of rhabdomyolysis associated with rosuvastatin in the post-marketing setting was higher with the 40 mg dose.
Creatine kinase level
Creatine kinase (CK) levels should not be measured after significant exercise or in the presence of possible alternative causes of CK elevation that may complicate interpretation of results. If initial CK levels are significantly elevated (> 5 times ULN), a repeat test should be performed within 5-7 days to confirm the results. If the results of the repeat test confirm that the initial CK value is more than 5 times ULN, the drug should not be started.
Before starting treatment
Rosuvastatin, like other HMG-CoA reductase inhibitors, should be administered with caution to patients with a predisposition to myopathy/rhabdomyolysis. Risk factors for this include:
renal impairment; hypothyroidism; personal or family history of hereditary muscle diseases; history of myotoxicity with other HMG-CoA reductase inhibitors or fibrates; alcohol abuse; age > 70 years;
situations that may lead to increased levels of the drug in the blood plasma (see sections “Pharmacokinetics”, “Interaction with other medicinal products and other types of interactions” and “Method of administration and dosage”);
concomitant use of fibrates.
In such patients, the risk of treatment should be weighed against the expected benefit; clinical monitoring is also recommended. If baseline CK levels are significantly elevated (> 5 times ULN), treatment should not be initiated.
Patients should be asked to report unexplained muscle pain, weakness or cramps immediately, especially if accompanied by malaise or fever. In such patients, CK levels should be measured. The drug should be discontinued if CK levels are significantly elevated (>5 × ULN) or if muscle symptoms are severe and cause daily discomfort (even if CK levels are ≤ 5 × ULN). If symptoms resolve and CK levels return to normal, rosuvastatin or an alternative HMG-CoA reductase inhibitor may be restarted at the lowest dose and under close observation. There is no need to monitor CK levels regularly in asymptomatic patients. Cases of immune-mediated necrotizing myopathy (IMNM) have been reported very rarely during or after treatment with statins, including rosuvastatin. Clinical manifestations of IONM include proximal muscle weakness and elevated serum creatine kinase levels, which persist even after discontinuation of statins.
It is known that in clinical studies in a small number of patients taking rosuvastatin and concomitant medications, an increased effect on skeletal muscle was not observed. However, an increased incidence of myositis and myopathy has been observed in patients taking other HMG-CoA reductase inhibitors together with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when used concomitantly with some HMG-CoA inhibitors. Therefore, the use of rosuvastatin in combination with gemfibrozil is not recommended. The benefits of further lipid changes when using rosuvastatin in combination with fibrates or niacin should be carefully weighed against the potential risks associated with the use of such combinations. The 40 mg dose is contraindicated with concomitant use of fibrates (see sections “Interaction with other medicinal products and other types of interactions” and “Adverse reactions”).
Rosuvastatin should not be used concomitantly with systemic fusidic acid or within 7 days of stopping fusidic acid. In patients in whom systemic fusidic acid is considered essential, statin treatment should be discontinued for the duration of fusidic acid treatment. Rhabdomyolysis (including some fatalities) has been reported in patients receiving the combination of fusidic acid and statins (see section 4.5). Patients should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness. Statin therapy may be restarted seven days after the last dose of fusidic acid. In exceptional cases where prolonged systemic fusidic acid is required, for example for the treatment of severe infections, the need for concomitant use of rosuvastatin and fusidic acid should only be considered on a case-by-case basis and under close medical supervision.
Rosuvastatin should not be used in patients with acute, serious conditions that suggest myopathy or the possibility of developing renal failure secondary to rhabdomyolysis (such as sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders or uncontrolled seizures).
Effect on the liver
Like other HMG-CoA reductase inhibitors, rosuvastatin should be used with caution in patients who abuse alcohol and/or have a history of liver disease.
It is recommended to check biochemical parameters of liver function before starting treatment and 3 months later. Rosuvastatin should be discontinued or the dose reduced if serum transaminase levels exceed three times the upper limit of normal. The frequency of reports of serious hepatic events (mainly increased hepatic transaminases) in the post-marketing period was higher with the 40 mg dose.
In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the underlying disease should be treated first before initiating therapy with rosuvastatin.
In the post-marketing period, fatal or non-fatal cases of hepatic failure have been reported rarely in patients taking statins, including rosuvastatin. If serious liver damage with clinical symptoms and/or hyperbilirubinemia or jaundice develops during treatment with rosuvastatin, the drug should be discontinued immediately. Unless other causes are identified, treatment with Rosister® should not be resumed.
Racial affiliation
It is known that in pharmacokinetic studies, an increase in exposure in patients of the Mongoloid race was observed, approximately twice as much as in Caucasians (see sections "Pharmacokinetics", "Contraindications" and "Method of administration and dosage").
Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. The benefit of lipid-lowering effects of rosuvastatin in HIV patients receiving protease inhibitors should be considered, as well as the possibility of increased plasma concentrations of rosuvastatin at the start of therapy and with an increase in the dose of rosuvastatin in patients receiving protease inhibitors. Co-administration of the drug with some protease inhibitors is not recommended unless the dose of rosuvastatin is adjusted (see sections “Interaction with other medicinal products and other forms of interaction” and “Method of administration and dosage”).
Lactose intolerance
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Interstitial lung disease
Exceptional cases of interstitial lung disease have been reported with the use of some statins, particularly with long-term treatment (see section 4.8). Symptoms of this disease may include dyspnoea, non-productive cough and general deterioration (fatigue, weight loss and fever). If interstitial lung disease is suspected, statins should be discontinued.
Diabetes mellitus
There is some evidence that statins as a class increase blood glucose levels and in some patients at high risk of future diabetes mellitus may cause hyperglycemia to a level requiring appropriate treatment of diabetes mellitus. However, this risk is outweighed by the reduced risk of vascular events with statins and should not be a reason to discontinue statin therapy. Patients at risk (fasting glucose 5.6-6.0 mmol/l, BMI >30 kg/m2, elevated triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.
The overall incidence of diabetes mellitus reported in the study was 2.8% in the rosuvastatin group and 2.3% in the placebo group, predominantly in patients with fasting glucose levels between 5.6 and 6.9 mmol/L.
Children
Assessment of linear growth (height), body weight, BMI (body mass index) and secondary sexual maturation characteristics according to Tanner in children aged 10 to 17 years who took rosuvastatin is limited to a period of 1 year. It is known that after 52 weeks of study treatment, no effect on growth, body weight, BMI or sexual maturation was detected (see section "Pharmacodynamics"). Clinical trial experience in children and adolescents is limited, and the long-term effects of rosuvastatin use (> 1 year) on sexual maturation are unknown.
In children and adolescents taking rosuvastatin for 52 weeks, an increase in CK levels > 10 times the upper limit of normal and muscle symptoms after physical exertion or increased physical activity were observed more often compared to those in adults (see section "Adverse reactions").
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effect of rosuvastatin on the ability to drive and use machines have not been conducted. However, given the pharmacodynamic properties of the drug, it is unlikely that rosuvastatin will affect this ability. When driving or operating other mechanisms, the possibility of dizziness during treatment should be taken into account.
Use during pregnancy or breastfeeding
Rosuvastatin is contraindicated during pregnancy or breastfeeding.
Women of reproductive age should use adequate contraception.
Since cholesterol and other cholesterol biosynthesis products play an essential role in fetal development, the potential risk of inhibition of HMG-CoA reductase outweighs the benefits of using the drug during pregnancy. Animal data on reproductive toxicity are limited. If the patient becomes pregnant while taking this drug, treatment should be discontinued immediately.
Because another drug of this class is excreted in human milk and because HMG-CoA reductase inhibitors can cause serious adverse reactions in nursing infants, women requiring treatment with rosuvastatin should be advised to refrain from breast-feeding. There are no data on the excretion of the drug in human milk (see section 4.3).
Method of administration and doses
Before starting treatment, the patient should be placed on a standard cholesterol-lowering diet and should continue to follow it throughout treatment. The dose should be individualized according to the goals of therapy and the patient's response.
