Roxera film-coated tablets 10 mg blister No. 90

Instructions for Roxera film-coated tablets 10 mg blister No. 90

Composition

active ingredient: 1 film-coated tablet contains 10 mg of rosuvastatin (as rosuvastatin calcium);

excipients: microcrystalline cellulose, anhydrous lactose, crospovidone, anhydrous colloidal silicon dioxide, magnesium stearate;

film coating: methacrylate copolymer, macrogol 6000, titanium dioxide (E 171), lactose monohydrate.

Dosage form

Film-coated tablets.

Main physicochemical properties: white, round, slightly biconvex, film-coated tablets with beveled edges and engraved with "10" on one side.

Pharmacotherapeutic group

Lipid-lowering agents. HMG-CoA reductase inhibitors.

ATX code C10A A07.

Pharmacological properties

Pharmacodynamics

Rosuvastatin reduces elevated LDL-cholesterol, total cholesterol, and triglycerides and increases high-density lipoprotein (HDL) cholesterol. It also significantly reduces apolipoprotein B, low-density lipoprotein (LDL) cholesterol, VLDL-cholesterol, VLDL-triglycerides, and increases apolipoprotein A-I. Roxera® also reduces the LDL-cholesterol/HDL-cholesterol, total cholesterol/HDL-cholesterol, and LDL-cholesterol/HDL-cholesterol ratios, as well as apolipoprotein B/apolipoprotein A-I.

The therapeutic effect is achieved within 1 week after the start of treatment, and 90% of the maximum treatment effect is achieved after 2 weeks. The maximum effect is usually achieved after 4 weeks and is maintained throughout the course of treatment.

Pharmacokinetics

Absorption

Peak plasma concentrations of rosuvastatin are reached approximately 5 hours after oral administration. Absolute bioavailability is approximately 20%.

Distribution

Rosuvastatin is extensively metabolized in the liver, which is the primary site of cholesterol synthesis and LDL-cholesterol clearance. The volume of distribution of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is bound to plasma proteins, primarily albumin.

Metabolism

Rosuvastatin undergoes limited metabolism (approximately 10%). In vitro metabolism studies using human hepatocytes indicate that rosuvastatin undergoes only minimal P450-mediated metabolism and that this metabolism is not clinically relevant. CYP2C9 was the major isoenzyme involved in metabolism, with 2C19, 3A4 and 2D6 being involved to a lesser extent. The major metabolites identified are the N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximately 50% less active than rosuvastatin, the lactone form is considered clinically inactive. Rosuvastatin has more than 90% inhibitory activity against HMG-CoA reductase circulating in the general circulation.

Breeding

Approximately 90% of a rosuvastatin dose is excreted unchanged in the feces (consisting of absorbed and unabsorbed active substance), and the remainder is excreted in the urine. Approximately 5% is excreted unchanged in the urine. The plasma half-life is approximately 20 hours. The half-life does not increase with high doses. The geometric mean plasma clearance is approximately 50 liters/hour (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, hepatic uptake of rosuvastatin involves the membrane transporter OATP-C. This transporter is important for the elimination of rosuvastatin from the liver.

Linearity

Systemic exposure to rosuvastatin increases in proportion to the dose. There is no change in pharmacokinetic parameters after multiple daily administration.

Patient groups

Race

Pharmacokinetic studies demonstrate an approximately 2-fold increase in AUC and Cmax of rosuvastatin in patients of Asian origin (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with patients of the Caucasian race; in Indians, an approximately 1.3-fold increase in mean AUC and Cmax values is observed. Pharmacokinetic analysis of the patient group did not reveal any clinically significant differences in pharmacokinetics between representatives of the Caucasian and Negroid races.

Kidney failure

In a study involving patients with varying degrees of renal impairment, mild to moderate renal disease had no effect on the plasma concentrations of rosuvastatin or the N-desmethyl metabolite. In patients with severe renal impairment (creatinine clearance < 30 ml/min), plasma concentrations increased 3-fold and the N-desmethyl metabolite concentrations increased 9-fold compared with healthy volunteers. Steady-state plasma concentrations of rosuvastatin in patients undergoing hemodialysis were approximately 50% higher than in healthy volunteers.

Liver failure

In a study involving patients with varying degrees of hepatic impairment, there was no evidence of increased exposure to rosuvastatin in patients with Child-Pugh scores of 7 or less. However, at least a 2-fold increase in systemic exposure was observed in two patients with Child-Pugh scores of 8 and 9.

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

Doses of 5 mg, 10 mg, 15 mg and 20 mg are contraindicated:

patients with hypersensitivity to rosuvastatin or to any inactive ingredient; patients with active liver disease, including those of unknown etiology, persistent elevations of serum transaminases and elevations of any serum transaminase more than 3 times the upper limit of normal; patients with severe renal impairment (creatinine clearance < 30 ml/min); patients with myopathy; patients taking concomitant cyclosporine; patients with pre-existing risk factors for myotoxic complications; during pregnancy or breastfeeding, as well as women of reproductive age not using appropriate contraception; children under 10 years of age.

Interaction with other medicinal products and other types of interactions

Rosuvastatin is a substrate for certain transport proteins, including OATP1B1, which provides hepatic transport, and the efflux transporter BCRP. Simultaneous administration of Roxera® with drugs that are inhibitors of these transport proteins may lead to an increase in the concentration of rosuvastatin in the blood plasma and an increase in the risk of myopathy.

When it is necessary to use Roxera® together with other drugs that increase the exposure of rosuvastatin, the dose of Roxera® should be adjusted. It should be started with a dose of 5 mg once a day if an increase in exposure (AUC) of approximately 2 times or more is expected. The maximum daily dose of Roxera® should be adjusted so that the expected exposure of rosuvastatin does not exceed the concentration observed when taking a daily dose of 40 mg of Roxera® in the absence of drug interactions. For example, a dose of 5 mg of Roxera® with simultaneous use with cyclosporine (7.1-fold increase in exposure), a dose of 10 mg of Roxera® with simultaneous use with a combination of ritonavir/atazavir (3.1-fold increase), and a dose of 20 mg of Roxera® with simultaneous use with gemfibrozil (1.9-fold increase).

Antacids

Co-administration of rosuvastatin with an antacid suspension containing aluminum and magnesium hydroxide resulted in a decrease in plasma concentrations of rosuvastatin by approximately 50%. This effect was reduced when the antacid was taken 2 hours after rosuvastatin. The clinical significance of this interaction has not been studied.

Fenofibrates, fibric acid derivatives

Although no pharmacokinetic interaction has been observed between rosuvastatin and fenofibrate, a pharmacodynamic interaction may occur. Gemfibrozil, fenofibrate and other fibric acids, including nicotinic acid, may increase the risk of myopathy when administered concomitantly with HMG-CoA reductase inhibitors.

Cyclosporine

During concomitant use of Roxera® and cyclosporine, rosuvastatin AUC values were on average approximately 7 times higher than those observed in healthy volunteers (see Table 2). Roxera® is contraindicated in patients receiving cyclosporine concomitantly (see section "Contraindications").

Concomitant use did not affect the plasma concentrations of cyclosporine.

Vitamin K antagonists

As with other HMG-CoA reductase inhibitors, initiation of treatment with Roxera® or gradual dose increase in patients concomitantly receiving vitamin K antagonists (e.g. warfarin or other coumarin anticoagulants) may lead to an increase in the International Normalized Ratio (INR). After discontinuation of Roxera® or dose reduction, INR may decrease. In such cases, it is advisable to monitor INR appropriately. In patients receiving vitamin K antagonists, it is recommended to monitor INR both at the beginning of treatment with Roxera® and after discontinuation or with subsequent dose changes.

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 AUC and Cmax of rosuvastatin by approximately 3 and 7 times, respectively. The simultaneous use of Roxera® and some combinations of protease inhibitors is possible after careful consideration of the dose adjustment of Roxera®, based on the expected increase in rosuvastatin exposure (see sections “Method of administration and dosage”, “Special instructions for use”, “Interaction with other medicinal products and other forms of interaction”, Table 2).

Gemfibrozil and other lipid-lowering drugs

Simultaneous use of Roxera® and gemfibrozil led to a 2-fold increase in rosuvastatin AUC and Cmax (see section "Special instructions").

Based on data from specific interaction studies, no significant pharmacokinetic interaction with fenofibrate is expected, but a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and niacin (nicotinic acid) in lipid-lowering doses (> or equal to 1 g/day) increase the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly because they can lead to myopathy when used alone. The dose of Roxera® 40 mg is contraindicated with concomitant use of fibrates.

Treatment with Roxera® in such cases should also be started with a dose of 5 mg.

Ezetimibe

Co-administration of Roxera® 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 Roxera® and ezetimibe, which could lead to adverse events, cannot be excluded (see section 4.4).

Erythromycin

Simultaneous use of Roxera® and erythromycin reduced the AUC(0-t) 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).

Table 2

Effect of concomitant medications on rosuvastatin exposure

(AUC; in descending order of magnitude) from published clinical trial data

* 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 ↓.

Oral contraceptives/hormone replacement therapy (HRT)

The simultaneous use of Roxera® and oral contraceptives led to an increase in the AUC of ethinylestradiol and norgestrel by 26% and 34%, respectively. The 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 Roxera® and HRT simultaneously, so the possibility of interaction cannot be excluded. However, this combination has been widely used in women in clinical trials and was well tolerated.

Other medicines

Based on data from specific studies, no clinically significant interaction with digoxin is expected.

In clinical studies, Roxera® was used concomitantly with antihypertensive, antidiabetic agents, and hormone replacement therapy. These studies did not show any evidence of clinically significant adverse interactions.

Fusidic acid

The risk of myopathy, including rhabdomyolysis, may be increased by concomitant systemic use of fusidic acid with statins. The mechanism of this interaction (pharmacodynamic or pharmacokinetic) is not yet known. There have been reports of rhabdomyolysis (including fatal outcomes) in patients receiving this combination.
If systemic treatment with fusidic acid is necessary, rosuvastatin should be discontinued for the entire period of fusidic acid treatment.

Lopinavir/ritonavir

In a pharmacological study, concomitant use of Roxera® and a combination drug 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 for rosuvastatin, respectively. Interactions between Roxera® 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

In patients taking Roxera® in high doses, especially 40 mg, cases of proteinuria (determined by the "strip test"), mainly tubular in origin and in most cases temporary or short-lived, have been reported. Proteinuria did not indicate acute or progressive renal disease. Adverse renal events in the post-marketing period were more common with the 40 mg dose. In patients taking the drug in a dose of 30 or 40 mg, renal function should be checked regularly.

Effects on skeletal muscles

Skeletal muscle disorders, such as myalgia, myopathy, and rarely rhabdomyolysis, have been observed in patients taking all doses of Roxera®, and especially at doses above 20 mg. Very rare 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, and therefore such a combination should be used with caution.

As with other HMG-CoA reductase inhibitors, cases of rhabdomyolysis associated with the use of Roxera® in the post-marketing period occurred more often at a dose of 40 mg. There are reports of rare cases of immune-mediated necrotizing myopathy, clinically manifested by persistent proximal muscle weakness and increased serum creatine kinase, during treatment or after discontinuation of treatment with statins, including rosuvastatin. In such cases, additional neuromuscular and serological studies, treatment with immunosuppressive drugs may be necessary.

Determination of creatine phosphokinase level

Creatine phosphokinase levels should not be measured after significant exercise or when there are possible alternative causes of elevated creatine phosphokinase that could interfere with interpretation of the results. If initial creatine phosphokinase levels are significantly elevated (>5x upper limit of normal), additional confirmatory testing should be performed within 5-7 days. If the result of a repeat test confirms an initial level >5x upper limit of normal, treatment should not be initiated.

Before treatment

Roxera®, like other HMG-CoA reductase inhibitors, should be administered with caution to patients with factors predisposing to the development of myopathy/rhabdomyolysis. Such factors include:

renal impairment; hypothyroidism; personal or family history of hereditary muscle diseases; history of myotoxicity caused by other HMG-CoA reductase inhibitors or fibrates; alcohol abuse; age >70 years; situations that may lead to increased plasma levels of the drug; concomitant use of fibrates.

In such patients, the risk and potential benefit of the drug should be weighed; clinical monitoring is also recommended. Treatment should not be initiated in cases of significantly elevated baseline CPK levels (>5 x ULN).

Patients should be advised to report unexplained muscle pain, weakness or cramps immediately, especially if accompanied by malaise or fever. CPK levels should be measured in such patients. Treatment should be discontinued if CPK levels are significantly elevated (>5xULN) or if muscle symptoms are severe and cause discomfort in daily life (even if CPK levels are ≤ 5 xULN). If symptoms resolve and CPK levels return to normal, Roxer® or an alternative HMG-CoA inhibitor can be tried again, but in minimal doses and under close supervision. Regular monitoring of CPK levels in patients without the above symptoms is not necessary.

In clinical studies, a small number of patients taking Roxera® and concomitant medications did not show an increased effect on skeletal muscle. However, an increased incidence of myositis and myopathy was 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 reductase inhibitors, therefore Roxera® is not recommended for use in combination with gemfibrozil. The beneficial effect of further changes in lipid levels when using Roxera® with fibrates or niacin should be weighed against the potential risks of using such a combination. The simultaneous use of Roxera® at a dose of 30 or 40 mg and fibrates is contraindicated.

Roxera® should not be combined with systemic fusidic acid or within 7 days of stopping fusidic acid treatment. For patients for whom the use of systemic fusidic acid is considered necessary, statin treatment should be discontinued for the entire period of fusidic acid treatment. There have been reports of cases of rhabdomyolysis (including fatal outcomes) in patients receiving fusidic acid and statins in combination. The patient should immediately consult a doctor if he experiences symptoms such as muscle weakness, pain or flaccidity.
Statin therapy may be restarted 7 days after the last dose of fusidic acid.
In exceptional cases, when long-term systemic use of fusidic acid is necessary, for example, for the treatment of severe infections, the need for simultaneous administration of Roxera® and fusidic acid should be considered only on a case-by-case basis and under close medical supervision.

Roxera® should be used with caution in patients with factors predisposing to the development of myopathy, such as renal failure, old age, hypothyroidism, or in situations where the concentration of the drug in the blood plasma may increase.

Roxera® should not be used in patients with acute, serious conditions that contribute to the development of myopathy or increase the risk of developing renal failure on the background of rhabdomyolysis (such as sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine or electrolyte disorders; uncontrolled seizures).

Effect on the liver

Like other HMG-CoA reductase inhibitors, Roxera® should be used with caution in patients who abuse alcohol and/or have a history of liver disease.

It is recommended to check liver function before starting the drug and after 3 months of treatment. If the level of transaminases in the blood serum exceeds three times the upper limit of normal, the use of Roxera® should be discontinued. Serious liver function disorders (mainly increased levels of hepatic transaminases) in the post-marketing period have been reported more often with a dose of 40 mg.

In patients with secondary hypercholesterolemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should first be treated and then Roxera® should be started.

In the post-marketing period, there have been rare reports of fatal or non-fatal cases of hepatic failure in patients taking statins, including rosuvastatin. If serious liver damage develops during treatment with Roxera® with clinical symptoms and/or hyperbilirubinemia or jaundice, the drug should be discontinued immediately. If no other causes are identified, treatment with Roxera® should not be resumed.

Race

In pharmacokinetic studies, an increase in systemic exposure was observed in patients of Mongoloid race compared to Caucasians.

For such patients, dosage adjustment of Roxera® is necessary (see sections “Method of administration and doses” and “Pharmacokinetics”). For patients of the Mongoloid race, the initial dose of Roxera® should be 5 mg. Increased plasma concentrations of rosuvastatin have been observed in Asian patients (see section “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.

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 Roxera® 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 Roxera® in patients receiving protease inhibitors. Simultaneous use of the drug with protease inhibitors is not recommended unless the dose of Roxera® 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.

Interstitial lung disease

Isolated cases of interstitial lung disease have been reported with some statins, particularly with long-term therapy. Symptoms include dyspnea, nonproductive cough, and worsening of general condition (fatigue, weight loss, and fever). If a patient is suspected of developing interstitial lung disease, statin use 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 studies, the overall incidence of diabetes mellitus was 2.8% in the rosuvastatin group and 2.3% in the placebo group, mainly 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 Roxera® as monotherapy does not cause a decrease in the basal concentration of cortisol in the blood plasma and does not affect the adrenal reserve. Caution is required when using Roxera® simultaneously with other drugs that can reduce the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone and cimetidine.

Children and adolescents aged 10 to 17 years

The effect of rosuvastatin on linear growth (height), body weight, BMI (body mass index) and development of secondary sexual characteristics according to the Tanner scale in children aged 10-17 years was evaluated for only one year. After 52 weeks of study treatment, no effect on growth, body weight, BMI or sexual maturation 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 sexual maturation 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

No studies have been conducted to determine the effect of rosuvastatin on the ability to drive and use machines. Based on the pharmacodynamic properties of rosuvastatin, the likelihood of such an effect is insignificant. However, when driving and using machines, it should be taken into account that dizziness may occur during treatment.

Use during pregnancy or breastfeeding

The safety of Roxera® during pregnancy or breastfeeding has not been studied.

Roxera® is contraindicated during pregnancy or breastfeeding.

Women of reproductive age should use appropriate contraceptive measures while taking Roxera®.

Since cholesterol and other cholesterol biosynthesis products are essential for fetal development, the potential risk of HMG-CoA reductase inhibition outweighs the possible benefit of using the drug during pregnancy. If the patient becomes pregnant while taking the drug, treatment should be discontinued immediately.

Since 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 who require treatment with Roxera® should be advised to refrain from breastfeeding. There are no data on the excretion of the drug in human milk (see section "Contraindications").

Method of administration and doses

Before starting treatment, the patient should be placed on a standard hypocholesterolemic diet, which should be followed throughout treatment. The dose should be selected individually, depending on the goal of therapy and the effectiveness of treatment, using current agreed recommendations.

Roxera® 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.

Treatment of hypercholesterolemia

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 be based on 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 to the next dose after 4 weeks. Since adverse reactions are more common with the 40 mg dose than with lower doses, titration to 30 mg or 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 30 mg or 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 necessary based on age.

Use in children

The usual dose for children and adolescents with heterozygous familial hypercholesterolemia is 5-20 mg orally once daily. The dose should be titrated appropriately to achieve a therapeutic effect. The safety and efficacy of doses greater than 20 mg have not been studied in this population.

Dosage for patients with renal impairment

For patients with mild and moderate renal impairment, no dose adjustment is necessary. The recommended initial dose for patients with moderate renal impairment (creatinine clearance <60 ml/min) is 5 mg. The 30 mg and 40 mg doses are contraindicated in patients with moderate renal impairment. In patients with severe renal impairment, Roxera® is contraindicated in 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 with a Child-Pugh score of 8 and 9. Such patients should have their renal function assessed. There is no experience with the use of the drug in patients with a Child-Pugh score of 9. Roxera® is contraindicated in patients with active liver disease. In patients with severe liver dysfunction, an increase in exposure to rosuvastatin was observed, therefore, Roxera® 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, compared with the SLCO1B1 c.521TT and ABCG2 c.421CC genotypes, are associated with increased exposure (AUC) to rosuvastatin. For patients with the c.521CC or c.421AA genotypes, the maximum recommended daily dose of Roxera® 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 Roxera is taken simultaneously with certain drugs that can increase rosuvastatin plasma concentrations due to interaction with these transport proteins (e.g. cyclosporine and some protease inhibitors, including ritonavir).