Rozulip film-coated tablets 10 mg blister No. 28

Instructions for use Rozulip film-coated tablets 10 mg blister No. 28

Composition

active ingredient: rosuvastatin;

1 film-coated tablet contains 10.68 mg of rosuvastatin zinc (equivalent to 10 mg of rosuvastatin);

Excipients: lactose monohydrate, povidone, crospovidone, magnesium stearate, polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc.

Dosage form

Film-coated tablets.

Main physicochemical properties: white or almost white, round, slightly biconvex tablets, film-coated, engraved with a stylized letter E on one side and the number 592 on the other, odorless or almost odorless.

Pharmacotherapeutic group

Drugs that lower serum cholesterol and triglyceride levels. HMG-CoA reductase inhibitors. ATX code C10A A07.

Pharmacological properties

Pharmacodynamics

Rosuvastatin is a selective competitive inhibitor of HMG-CoA reductase, an enzyme that regulates the rate of conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A to mevalonate, a precursor of cholesterol.

The main target of rosuvastatin is the liver, where cholesterol synthesis occurs.

Rosuvastatin increases the number of hepatic LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which leads to increased uptake and catabolism of LDL and, in turn, leads to inhibition of very low density lipoprotein (VLDL) synthesis, thereby reducing total LDL and VLDL.

Rosuvastatin reduces elevated LDL-cholesterol, total cholesterol, and triglycerides, and slightly increases high-density lipoprotein (HDL) cholesterol. It also reduces apolipoprotein B, non-HDL-cholesterol, VLDL-cholesterol, VLDL-triglycerides, and slightly increases apolipoprotein A-I. Rosuvastatin also reduces the LDL-cholesterol/HDL-cholesterol ratio, total cholesterol/HDL-cholesterol, non-LDL-cholesterol/HDL-cholesterol ratio, and the apolipoprotein B/apolipoprotein A-I ratio.

The therapeutic effect is manifested within 1 week after the start of rosuvastatin therapy, after 2 weeks of treatment the effect reaches 90% of the maximum possible. The maximum effect is usually achieved 4 weeks after the start of treatment.

Pharmacokinetics

Absorption.

Cmax of rosuvastatin in blood plasma is reached approximately 5 hours after oral administration. Bioavailability is approximately 20%.

Distribution.

The volume of distribution of rosuvastatin is approximately 134 L. Almost 90% of rosuvastatin binds to plasma proteins, mainly albumin.

Metabolism.

Rosuvastatin undergoes limited metabolism (approximately 10%). Rosuvastatin is a weak substrate for metabolism by cytochrome P450 enzymes.

The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9.

CYP2C19, CYP3A4 and CYP2D6 enzymes are less active. The main metabolites of rosuvastatin identified are N-desmethyl and lactone metabolites. N-desmethyl is approximately 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity directed at inhibiting circulating HMG-CoA reductase is provided by rosuvastatin.

Breeding.

Approximately 90% of a rosuvastatin dose is excreted unchanged in the feces (including absorbed and unabsorbed rosuvastatin). The remainder of the active substance is excreted in the urine. Almost 5% is found in the urine unchanged. The elimination half-life is approximately 19 hours. The elimination half-life does not change with increasing dose. The geometric mean clearance is approximately 50 l/h (coefficient of variation 21.7%).

As with other HMG-CoA reductase inhibitors, the membrane cholesterol transporter OATP-C is involved in the hepatic uptake of rosuvastatin. The transporter 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 after multiple daily doses.

Special patient groups.

Age and gender have no clinically significant effect on the pharmacokinetics of rosuvastatin.

Ethnic groups. Comparative studies of the pharmacokinetics of rosuvastatin in patients of the Mongoloid race showed an increase in AUC and Cmax approximately twice as much as in representatives of the Caucasian race living in Europe and Asia.

No genetic or environmental factors were found to influence the differences in pharmacokinetic parameters. Pharmacokinetic analysis of different ethnic groups did not reveal clinically significant differences in pharmacokinetics between Caucasian and Mongoloid patients.

Patients with hepatic impairment. Among patients with varying degrees of hepatic impairment, no increase in the half-life of rosuvastatin was observed if the Child-Pugh score did not exceed 7. However, in two patients with Child-Pugh scores of 8 and 9, an increase in the half-life of at least twofold was observed.

There is no experience with the use of rosuvastatin in patients with a score above 9 on the Child-Pugh scale.

Indication

Treatment of hypercholesterolemia

Adults, adolescents and children aged 10 years and over with primary hypercholesterolemia (type IIa, excluding familial heterozygous 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 (see section 5.1), as an adjunct to correction of other risk factors.

Contraindication

Hypersensitivity to the active substance 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); severe renal impairment (creatinine clearance < 30 ml/min); myopathy; concomitant use of cyclosporine; children; women of reproductive age not using effective contraception.

The 40 mg dose is contraindicated in patients who are at increased risk of developing myopathy/rhabdomyolysis. These factors include:

moderate renal insufficiency (creatinine clearance < 60 ml/min); hypothyroidism; personal or family history of hereditary muscle diseases; history of myotoxicity caused by other HMG-CoA reductase inhibitors or fibrates; alcohol abuse; conditions that may lead to increased plasma concentrations of rosuvastatin; Mongoloid race; concomitant use of fibrates.

Interaction with other medicinal products and other types of interactions

Effect of concomitant medications on rosuvastatin

Transport protein inhibitors

Rosuvastatin is a substrate for several transport proteins, including the hepatic uptake transporter OATP1B1 and the efflux transporter BCRP. Concomitant use of Rosuvastatin with medicinal products that inhibit these transport proteins may lead to increased plasma concentrations of rosuvastatin and an increased risk of myopathy (see sections 4.2, 4.4, and 4.5).

Cyclosporine

During concomitant use of Rozulip® and cyclosporine, rosuvastatin AUC values were on average approximately 7 times higher than those observed in healthy volunteers (see Table 2). Rozulip® 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 2). For example, in a pharmacokinetic 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 rosuvastatin AUC and Cmax by approximately 3 and 7 times, respectively. Co-administration of Rosuvastatin and some combinations of protease inhibitors may be considered after careful consideration of the dose adjustment of Rosuvastatin based on the expected increase in rosuvastatin exposure (see sections 4.2, 4.4, and 4.5, Table 2).

Gemfibrozil and other lipid-lowering agents

Concomitant use of Rosulip® and gemfibrozil resulted in a 2-fold increase in rosuvastatin AUC and Cmax (see section "Special warnings and precautions for use").

Based on specific studies, no pharmacokinetically significant interaction with fenofibrate is expected, but a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses (> or equal to 1 g/day) of niacin (nicotinic acid) increase the risk of myopathy when used concomitantly with HMG-CoA inhibitors, presumably because they can cause myopathy when used alone. The 40 mg dose is contraindicated with concomitant use of fibrates (see sections 4.3 and 4.4). These patients should also be started on the 5 mg dose.

Co-administration of Rosuvastatin 10 mg and ezetimibe 10 mg in patients with hypercholesterolemia resulted in a 1.2-fold increase in rosuvastatin AUC (Table 2). A pharmacodynamic interaction between Rosuvastatin and ezetimibe, which could lead to adverse events, cannot be excluded (see section 4.4).

Antacids

Co-administration of Rosuvastatin with antacid suspensions containing aluminum or magnesium hydroxide decreased 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 Rosulip® and erythromycin reduced the AUC of rosuvastatin by

20% and Cmax by 30%. This interaction may be caused by increased intestinal peristalsis due to the action of 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 Rozulip® with other drugs that can increase the exposure of rosuvastatin, the dose of Crestor should be adjusted. If the exposure of the drug (AUC) is expected to increase by approximately 2 or more times, the use of Rozulip® should be started at a dose of 5 mg once a day. The maximum daily dose of Rozulip® should be adjusted so that the expected exposure of rosuvastatin does not exceed the exposure observed when taking a dose of 40 mg / day without the use of drugs that interact with the drug; for example, when used with gemfibrozil, the dose of Rozulip® will be 20 mg (an increase in exposure of 1.9 times), when used with a combination of ritonavir / atazanavir - 10 mg (an increase of 3.1 times), When used simultaneously with cyclosporine - 5 mg (an increase of 7.1 times).

Table 2. Effect of concomitant medications on rosuvastatin exposure (AUC; in descending order) based on published clinical trial data

* Data reported as x-fold change represents the ratio between rosuvastatin in combination and alone. Data reported as % change represents the % difference relative to rosuvastatin alone.

Increase is indicated by ↑, no change by ↔, decrease by ↓.

** Several interaction studies were conducted at different doses of Rosulip®, the most significant correlation is presented in the table.

Effect of rosuvastatin on concomitant medications

As with other HMG-CoA reductase inhibitors, when starting or increasing the dose of Rosuvastatin in patients receiving concomitant vitamin K antagonists (e.g. warfarin or other coumarin anticoagulants), 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 recommended.

Oral contraceptives/hormone replacement therapy (HRT)

Co-administration of Rosulip® 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 the drugs in patients taking Rosulip® and HRT simultaneously, so a similar effect cannot be excluded. However, the combination has been widely used in women in clinical trials and was well tolerated.

Other medicines

According to special studies, clinically significant interactions with digoxin are not expected.

Fusidic acid:

The risk of myopathy, including rhabdomyolysis, may be increased when fusidic acid is used concomitantly with statins.

Lopinavir/ritonavir

In a pharmacological study, concomitant use of Rosuvastatin and a combination product containing two protease inhibitors (lopinavir 400 mg/ritonavir 100 mg) in healthy volunteers was associated with an approximately two-fold and five-fold increase in steady-state AUC(0-24) and Cmax of rosuvastatin, respectively. Interactions between Rosuvastatin and other protease inhibitors have not been studied.

Children

Interaction studies have only been conducted in adults. The extent of interaction in children is unknown.

Application features

Effects on the kidneys

Proteinuria, detected by dipstick analysis and predominantly of tubular origin, has been observed in patients treated with higher doses of Rosuvastatin, including 40 mg, and in most cases was transient or intermittent. Proteinuria was not a harbinger of acute or progressive renal disease (see section 4.8). The frequency of reports of serious renal events in post-marketing studies is higher with the 40 mg dose. In patients taking the drug at a dose of 40 mg, renal function should be monitored regularly during follow-up.

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 at doses above 20 mg. Isolated cases of rhabdomyolysis have been reported with the use of ezetimibe 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 the use of Rosuvastatin in the post-marketing setting was higher with the 40 mg dose. Rare cases of immune-mediated necrotizing myopathy, clinically manifested by persistent proximal muscle weakness and elevated serum creatine kinase, have been reported during or after discontinuation of statins, including rosuvastatin. In such cases, additional neuromuscular and serological testing and treatment with immunosuppressive agents may be warranted.

Creatine kinase level

Creatine kinase (CK) levels should not be measured after significant exercise or when alternative causes of CK elevation are possible, which 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

Rosulip®, 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 blood plasma (see sections “Method of administration and dosage”, “Interaction with other medicinal products and other types of interactions” and “Pharmacokinetics”);

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 the 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 x ULN) or if muscle symptoms are severe and cause daily discomfort (even if CK levels are ≤ 5 x ULN). If symptoms resolve and CK levels return to normal, therapy with Crestor or an alternative HMG-CoA reductase inhibitor may be resumed at the lowest dose and under close supervision. There is no need to regularly monitor CK levels in asymptomatic patients. Very rare cases of immune-mediated necrotizing myopathy (IMNM) have been reported 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.

In clinical studies, there was no evidence of increased effects on skeletal muscle in a small number of patients taking Rosulip® and concomitant medications. However, an increased incidence of myositis and myopathy has been observed in patients taking other HMG-CoA reductase inhibitors 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 Rosulip® in combination with gemfibrozil is not recommended. The benefits of further lipid-lowering effects of Rosulip® 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”).

Rosulip® 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, Rosulip® should be used with caution in patients who abuse alcohol and/or have a history of liver disease.

It is recommended to check biochemical indicators of liver function before starting treatment and 3 months later. The use of the drug Rosulip® should be discontinued or the dose reduced if the level of transaminases in the blood serum exceeds three times the upper limit of normal. The frequency of reports of serious liver events (mainly increased levels of hepatic transaminases) in the post-marketing period was higher with the use of a dose of 40 mg.

In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the underlying disease should be treated first before initiating therapy with Rosulip®.

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 develops during treatment with Rosulip® with clinical symptoms and/or hyperbilirubinemia or jaundice, immediately discontinue the drug. Unless other causes are identified, treatment with Rosulip® should not be resumed.

Race

Pharmacokinetic studies indicate an increase in exposure in patients of the Mongoloid race by approximately two times compared to Europeans. For such patients, dosage adjustment of the drug Rosulip® is necessary (see sections “Dosage and Administration”, “Contraindications” and “Pharmacokinetics”). For patients of the Asian race, the initial dose of Rosulip® should be 5 mg. Increased plasma concentrations of rosuvastatin have been observed in Asian patients (see sections “Special Instructions for Use” and “Pharmacokinetics”). Increased systemic exposure should be taken into account when treating patients of the Mongoloid race, in whom hypercholesterolemia is not adequately controlled with doses up to 20 mg.

Protease inhibitors

Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. The benefit of lowering lipid levels with Rozulip® in HIV patients receiving protease inhibitors should be considered, as well as the possibility of increasing rosuvastatin plasma concentrations at the beginning of therapy and with increasing doses of Rozulip® in patients receiving protease inhibitors. Concomitant use of the drug with protease inhibitors is not recommended unless the dose of Rozulip® is adjusted (see sections “Method of administration and dosage” and “Interaction with other medicinal products and other types of interactions”).

Lactose intolerance

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Exceptional cases of interstitial lung disease have been reported with some statins, particularly with long-term treatment (see section 4.8). Symptoms may include dyspnoea, non-productive cough and general malaise (fatigue, weight loss and fever). If interstitial lung disease is suspected, statins should be discontinued.

Diabetes mellitus

There is some evidence that statins increase blood glucose levels and in some patients at high risk of future diabetes, may cause hyperglycemia to a level requiring appropriate diabetes management. 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.

In the JUPITER study, the overall incidence of diabetes mellitus 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.

As with other HMG-CoA reductase inhibitors, increases in HbA1c and serum glucose levels have been observed with rosuvastatin. In some cases, these values may exceed the threshold for diagnosing diabetes mellitus, especially in patients at high risk of developing diabetes.

In clinical studies, it has been shown that Rozulip® as monotherapy does not cause a decrease in basal plasma cortisol concentrations and does not affect adrenal reserve. Caution is required when using Rozulip® concomitantly with other drugs that can reduce the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone and cimetidine.

Children

Assessment of linear growth (height), body weight, BMI (body mass index) and secondary Tanner puberty characteristics in children aged 10 to 17 years who took rosuvastatin was limited to a period of 1 year. After 52 weeks of study treatment, no effect on growth, body weight, BMI or puberty was observed (see section 5.1). Clinical trial experience in children and adolescents is limited, and the long-term effects of rosuvastatin use (> 1 year) on puberty are unknown.

In a clinical study in children and adolescents taking rosuvastatin for 52 weeks, increases in CK levels >10 times the upper limit of normal and muscle symptoms after exercise or increased physical activity were observed more frequently compared to those in adults (see section "Adverse reactions").

Ability to influence reaction speed when driving vehicles or other mechanisms

Studies of the effect of Rozulip® on the ability to drive and use machines have not been conducted. However, given the pharmacodynamic properties of the drug, it is unlikely that Rozulip® will affect such ability. When driving or operating other mechanisms, the possibility of dizziness should be taken into account during treatment.

Use during pregnancy or breastfeeding

Rozulip® is contraindicated during pregnancy or breastfeeding.

Women of reproductive age should use appropriate contraception.

Since cholesterol and other cholesterol biosynthesis products play an essential role in fetal development, the potential risk from 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 receiving Rozulip should be advised not to breast-feed. 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, which should be followed throughout treatment. The dose should be individualized, depending on the goal of therapy and the effectiveness of treatment, following current consensus recommendations.

Rozulip can be taken at any time of the day, regardless of meals.

The tablet should not be chewed or crushed. Swallow the tablet whole with water.

The recommended starting dose is 5 or 10 mg orally once daily for both statin-naïve patients and patients previously treated with other HMG-CoA reductase inhibitors. The initial dose should take into account the individual patient's cholesterol level and future cardiovascular risk, as well as the potential risk of adverse reactions (see below). If necessary, the dose can be increased after 4 weeks. Since adverse reactions occur more frequently with the 40 mg dose than with lower doses, titration to the maximum dose of 40 mg should only be considered in patients with severe hypercholesterolemia and high cardiovascular risk (particularly those with familial hypercholesterolemia) who have not achieved the desired effect with the 20 mg dose and who should be monitored regularly. Specialist supervision is recommended when starting the 40 mg dose.

Prevention of cardiovascular disorders

In the cardiovascular risk reduction study, the daily dose was 20 mg. Patients with hypercholesterolemia should have standard lipid measurements and follow the dosing recommendations for the treatment of hypercholesterolemia.

Use in elderly patients

The recommended starting dose for patients over 70 years of age is 5 mg. No other dose adjustment is required based on age.

Dosage for patients with renal impairment

No dose adjustment is necessary for patients with mild to moderate renal impairment. The recommended starting dose for patients with moderate renal impairment (creatinine clearance <60 ml/min) is 5 mg. The 40 mg dose is contraindicated in patients with moderate renal impairment. In patients with severe renal impairment, the use of Rosulip® is contraindicated at any dose.

Dosage for patients with hepatic impairment

No increase in systemic exposure to rosuvastatin was observed in patients with a Child-Pugh score of 7. However, an increase in systemic exposure was noted in patients whose condition was assessed as 8 and 9 points on the Child-Pugh scale. Such patients should be assessed for renal function. There is no experience of using the drug in patients with a Child-Pugh score of 9. Rosulip® is contraindicated in patients with active liver disease. In patients with severe liver dysfunction, an increase in exposure to rosuvastatin was observed, therefore, Rosulip® should be used with caution in doses above 10 mg.

Race

Increased systemic exposure has been observed in patients of Mongoloid race. The recommended starting dose for patients of Asian origin is 5 mg. The use of a dose of 40 mg in such patients is contraindicated. The maximum daily dose is 20 mg.

Dosage for patients with a predisposition to developing myopathy.

The recommended starting dose for patients with a predisposition to myopathy is 5 mg.

The 40 mg dose is contraindicated in some of these patients.

The maximum daily dose is 20 mg.

Genetic polymorphism

The SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA genotypes are associated with increased exposure (AUC) to rosuvastatin compared to the SLCO1B1 c.521TT and ABCG2 c.421CC genotypes. For patients with the c.521CC or c.421AA genotypes, the maximum recommended daily dose of rosuvastatin is 20 mg.

Rosuvastatin is a substrate for various transport proteins (e.g. OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when Rosuvastatin is co-administered with certain medicinal products that may increase rosuvastatin plasma concentrations through interaction with these transport proteins (e.g. cyclosporine and some protease inhibitors, including combinations of ritonavir with atazanavir, lopinavir and/or tipranavir). If possible, alternative treatment should be considered and, if necessary, treatment with Rosuvastatin should be temporarily discontinued. In situations where co-administration of these medicinal products with Rosuvastatin cannot be avoided, the benefits and risks of concomitant treatment should be weighed and the dose of Rosuvastatin should be carefully selected.

Children

The drug should only be used in children by a specialist.

Use in children and adolescents aged 10 to 17 years (boys in Tanner stage II and above and girls who started menstruating at least a year ago).

Ordinary by