Rosucard, 90 pcs., 10 mg, film-coated tablets

Instructions for use of ROSUCARD®

Renal dysfunction

Proteinuria, detected using a test strip and mainly tubular in origin, was observed in patients receiving rosuvastatin in higher doses, namely 40 mg. Proteinuria is not a precursor to the development of acute or progressive renal failure. The incidence of serious renal impairment observed in post-marketing studies was higher at the 40 mg dose. Renal function should be assessed during routine examination of patients receiving the drug at a dose of 40 mg.

Musculoskeletal disorders

Musculoskeletal side effects such as myalgia, myopathy and, rarely, rhabdomyolysis have been observed in patients receiving rosuvastatin at any dose, particularly at doses greater than 20 mg. Rare cases of rhabdomyolysis have been observed in patients receiving ezetimibe in combination with HMG-CoA reductase inhibitors. A pharmacodynamic interaction between these drugs cannot be ruled out and caution should be exercised when using them together. As with other HMG-CoA reductase inhibitors, post-marketing reports of rhabdomyolysis with rosuvastatin were primarily associated with rosuvastatin 40 mg.

Control of creatine phosphokinase (CPK)

CPK levels should not be measured after heavy physical activity or if there is another reason for the increase in CPK levels, because this may lead to incorrect results. If the initial CPK level is significantly elevated (5 times the ULN), a repeat test should be performed within 5-7 days. If a repeat analysis confirms that the CPK level exceeds 5 times the normal level, treatment cannot be started.

Before treatment

The administration of rosuvastatin, like other HMG-CoA reductase inhibitors, is indicated with caution in patients with predisposing factors to the development of myopathy/rhabdomyolysis. These factors are:

• renal failure;
• hypothyroidism;
• patient or family history of muscle disorders;
• Providing a toxic effect on the muscles earlier when taking another HMG-CoA reductase inhibitor or fibrate;
• alcohol addiction;
• age over 70 years;
• situations in which an increase in plasma concentrations is possible;
• combined use with fibrates.

In such patients, the risk of therapy must be weighed against the expected effect, and inpatient monitoring is recommended. If the initial CPK level exceeds 5 times the normal CPK level, treatment cannot be started.

During treatment

Patients are advised to immediately report unexplained muscle pain, lethargy, or weakness, especially if accompanied by malaise or fever. CPK levels should be measured in these patients. Treatment should be discontinued if CPK levels exceed 5 times the normal CPK level or if muscle side effects are significant and cause daily discomfort (even if CPK levels exceed 5 times the normal CPK level). If symptoms resolve and CPK levels return to normal, rosuvastatin therapy may be resumed or another HMG-CoA reductase inhibitor at the lowest dose may be prescribed with careful monitoring of the patient. Routine monitoring of CPK levels in patients without these symptoms is not necessary.

In clinical trials, there was no evidence of an increase in musculoskeletal side effects in a small group of patients receiving rosuvastatin in combination with other drugs. However, an increase in the incidence of myositis and myopathy has been observed in patients receiving other HMG-CoA reductase inhibitors with fibrates, including gemfibrozil, cyclosporine, niacin, azole antifungals, protease inhibitors and macrolides. The use of gemfibrozil in combination with HMG-CoA reductase inhibitors increases the risk of developing myopathy. Therefore, concomitant use of rosuvastatin with gemfibrozil is not recommended. When using rosuvastatin together with fibrates or niacin, there are possible risks of side effects that should be taken into account when prescribing such combinations. The use of rosuvastatin at a dose of 40 mg is contraindicated when used together with fibrates. Rosuvastatin should not be administered to patients with acute conditions predisposing to the development of myopathy or with a predisposition to the development of renal failure due to rhabdomyolysis (eg, sepsis, hypotension, surgery, trauma, metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).

Side effects on the liver

Like other HMG-CoA reductase inhibitors, rosuvastatin should be used with caution in patients who consume excessive amounts of alcohol or have a history of liver disease. It is recommended to conduct a liver function test before starting treatment and during the first 3 months. In cases where the content of transaminases exceeds ULN by 3 times, treatment is canceled. The potential for liver effects (primarily increased transaminase levels) is greater at the 40 mg dose.

In patients with secondary hypercholesterolemia caused by hypothyroidism or nephrotic syndrome, treatment begins with compensation of the underlying disease (before starting rosuvastatin therapy).

Race

Pharmacokinetic studies have shown that the drug has a stronger effect on representatives of the Mongoloid race than on representatives of the Caucasian race.

Protease inhibitors

Concomitant use with protease inhibitors is not recommended.

Chronic lung diseases with connective tissue damage

Interstitial lung disease has been reported in exceptional cases with the use of some statins, especially during long-term treatment. Difficulty breathing, a dry cough, and general deterioration in health (fatigue, weight loss, and fever) may also occur. If interstitial lung disease is suspected, statin therapy should be discontinued.

Diabetes

Some evidence suggests that statins may increase blood glucose levels and, in patients predisposed to diabetes mellitus, may lead to a level of hyperglycemia at which diabetes treatment may be appropriate. However, the benefits of statin treatment outweigh this risk, and therefore discontinuation of statin therapy is not required. Patients at risk (fasting glucose level - 5.6-6.9 mmol/l, BMI>30 kg/m2, elevated triglyceride levels, hypertension) should be under careful clinical and biochemical supervision in accordance with national requirements. In a clinical study, the overall incidence of diabetes mellitus reports 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.

Children

Assessment of linear growth (height), body weight, BMI (body mass index) and secondary characteristics of puberty using the Tanner scale in children aged 10 to 17 years taking rosuvastatin is limited to a period of 1 year. After 52 weeks of the study, there was no effect of rosuvastatin treatment on height, weight, BMI or puberty. Clinical experience with the drug in children and adolescents is limited, and the long-term effect of rosuvastatin (more than 1 year) on puberty is unknown.

In clinical trials in children and adolescents taking rosuvastatin for 52 weeks, CPK levels were elevated (>10 times ULN) and muscle symptoms were more common post-exercise or following increased physical activity compared with observations in clinical trials in adults.

The drug contains lactose monohydrate, therefore the use of rosuvastatin is contraindicated in patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Impact on the ability to drive vehicles and operate machinery

Studies of the effect of rosuvastatin on the ability to drive a vehicle and control mechanical equipment have not been conducted. However, given the pharmacodynamic characteristics of the drug, caution should be exercised when driving vehicles or other mechanical vehicles (dizziness may occur during treatment with rosuvastatin).

Rosucard, 90 pcs., 10 mg, film-coated tablets

Inside,

without chewing or crushing, swallow whole with water at any time of the day, regardless of food intake.

Before starting therapy with Rosucard®, the patient should begin to follow a standard lipid-lowering diet and continue to follow it during treatment. The dose of the drug should be adjusted individually, depending on the indication and therapeutic response, taking into account current generally accepted recommendations for target lipid levels. If it is necessary to take the drug at a dose of 5 mg, the 10 mg tablet should be divided into 2 parts according to the risk.

The recommended starting dose of Rosucard® for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, is 5 or 10 mg 1 time per day.

When choosing the initial dose, one should be guided by the patient’s cholesterol level and take into account the risk of developing cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, after 4 weeks the dose of the drug can be increased.

Due to the potential for side effects when taking a dose of 40 mg compared to lower doses of the drug (see "Side Effects"), final titration to a maximum dose of 40 mg should only be done in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia) in whom the target cholesterol level was not achieved when taking a dose of 20 mg and who will be under medical supervision. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor. After 2–4 weeks of therapy and/or when the dose of Rosucard® is increased, it is necessary to monitor lipid metabolism parameters (if necessary, dose adjustment is required).

Patients with liver failure.

In patients with liver failure with Child-Pugh scores below 7 points, no dose adjustment of Rosucard® is required. The drug Rosucard® is contraindicated in patients with liver disease in the active phase, a persistent increase in serum activity of liver transaminases (more than 3 times compared to ULN) of unknown origin and patients with liver failure (severity from 7 to 9 points on the Child-Pugh scale ) (see “Contraindications”).

Patients with renal failure.

In patients with mild renal failure, no dose adjustment is required. The recommended initial dose of Rosucard® is 5 mg/day.

In patients with severe renal failure (creatinine clearance <30 ml/min), the use of Rosucard® is contraindicated.

In patients with moderate renal failure (creatinine clearance 30–60 ml/min), the use of Rosucard® at a dose of 40 mg/day is contraindicated (see “Contraindications”).

Elderly patients.

In patients over 65 years of age, no dose adjustment is required.

Special populations

Patients with a predisposition to myopathy.

The use of Rosucard® at a dose of 40 mg/day is contraindicated in patients with a predisposition to myopathy (see “Contraindications”). When prescribing doses of 10 and 20 mg/day, the recommended initial dose of Rosucard® for this group of patients is 5 mg/day.

Ethnic groups.

When studying the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was noted in representatives of the Mongoloid race (see “Pharmacokinetics”).

This fact should be taken into account when prescribing Rosucard® to patients of the Mongoloid race. When prescribing doses of 10 and 20 mg, the recommended initial dose of Rosucard® for this group of patients is 5 mg/day. The use of the drug Rosucard® at a dose of 40 mg/day in representatives of the Mongoloid race is contraindicated (see “Contraindications”).

When prescribing Rosucard® with gemfibrozil, the dose should not exceed 10 mg/day.

Genetic polymorphism.

Carriers of the SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA genotypes showed an increase in exposure (AUC) to rosuvastatin compared to carriers of the SLC01B1 c.521TT and ABCG2 c.421CC genotypes. For patients carrying genotypes c.521CC or c.421AA, the recommended maximum dose of Rosucard® is 20 mg/day (see “Pharmacokinetics”, “Special instructions” and “Interaction”).

Concomitant therapy.

Rosucard® binds to various transport proteins (in particular, OATP1B1 and BCRP). When simultaneous use of the drug Rosucard® with drugs (such as cyclosporine, some HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and/or tipranavir) that increase the concentration of rosuvastatin in the blood plasma due to interaction with transport proteins, the risk of developing myopathy may increase (including rhabdomyolysis) (see “Special Instructions” and “Interaction”). In such cases, the possibility of prescribing alternative therapy or temporarily stopping the use of Rosucard® should be assessed. If the use of the above drugs is necessary, you should read the instructions for use of the drugs before prescribing them simultaneously with the drug Rosucard®, assess the benefit-risk ratio of concomitant therapy and consider reducing the dose of the drug Rosucard® (see “Interaction”).

Rosecard

Use during pregnancy and breastfeeding

Rosucard® is contraindicated during pregnancy and lactation (breastfeeding).
The use of Rosucard® in women of reproductive age is possible only if reliable methods of contraception are used and if the patient is informed about the possible risk of treatment to the fetus.

Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibiting HMG-CoA reductase outweighs the benefit of using the drug during pregnancy. If pregnancy is diagnosed during drug therapy, the use of Rosucard® should be stopped immediately, and the patient should be warned about the potential risk to the fetus.

If it is necessary to use the drug during lactation, taking into account the possibility of adverse events in infants, the issue of stopping breastfeeding should be decided.

Use for liver dysfunction

Contraindications for tablets 10 and 20 mg: liver disease in the active phase or a persistent increase in the activity of liver transaminases in the serum (more than 3 times compared to ULN) of unknown origin; liver failure (severity from 7 to 9 points on the Child-Pugh scale).

Use for renal impairment

Contraindications for tablets 10 and 20 mg: severe renal dysfunction (creatinine clearance less than 30 ml/min); for 40 mg tablets: moderate renal failure (creatinine clearance 30-60 ml/min).

special instructions

During treatment, especially during the period of dose adjustment of the drug Rosucard®, the lipid profile should be monitored every 2-4 weeks and the dose of the drug should be changed if necessary.

It is recommended to determine liver function indicators before starting therapy and 3 months after starting therapy. The use of Rosucard® should be discontinued or the dose reduced if the level of hepatic transaminase activity in the blood serum is 3 times higher than the ULN.

When using the drug Rosucard® at a dose of 40 mg, it is recommended to monitor kidney function indicators.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of underlying diseases should be carried out before starting treatment with Rosucard®.

In patients with existing risk factors for the development of rhabdomyolysis, it is necessary to consider the balance of expected benefit and potential risk and conduct clinical monitoring throughout the course of treatment.

The patient should be informed to immediately report to the doctor the unexpected onset of muscle pain, muscle weakness or cramps, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CPK activity is significantly increased (more than 5 times the ULN) or if muscle symptoms are severe and cause daily discomfort. If symptoms disappear and CPK activity returns to normal, then re-prescribing Rosucard® or other HMG-CoA reductase inhibitors in lower doses should be considered with careful monitoring of the patient.

Determination of CPK activity should not be carried out after intense physical activity or in the presence of other possible reasons for increased CPK activity, which may lead to incorrect interpretation of the results obtained. If the initial CPK activity is significantly increased, then a repeat measurement should be taken after 5-7 days; therapy should not be started if a repeat test confirms the initial CPK activity (5 times higher than normal).

Routine monitoring of CPK activity in the absence of symptoms is impractical.

An increased incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrates (including gemfibrozil), cyclosporine, niacin, azole antifungals, protease inhibitors and macrolide antibiotics. The ratio of expected benefits and potential risks should be carefully weighed when using the drug Rosucard® and fibrates or nicotinic acid (at least 1 g / day); Co-administration of gemfibrozil is not recommended.

In most cases, proteinuria decreases or disappears during therapy and does not indicate the occurrence of acute or exacerbation of existing kidney disease. Renal function should be assessed during routine examination of patients receiving the drug at a dose of 40 mg.

Drugs of the statin class can cause an increase in blood glucose concentrations. In some patients at high risk of developing diabetes mellitus, such changes may lead to its manifestation, which is an indication for hypoglycemic therapy. However, the reduction in the risk of vascular diseases during the use of statins exceeds the risk of developing diabetes mellitus, so this factor should not serve as a basis for discontinuing statin treatment. Patients at risk (fasting glucose concentration 5.6-6.9 mmol/l, body mass index (BMI) >30 kg/m2, hypertriglyceridemia, history of arterial hypertension) should be under medical supervision and regularly monitor biochemical parameters.

The simultaneous administration of rosuvastatin and HIV protease inhibitors is not recommended.

Isolated cases of interstitial lung disease have been reported with long-term use of rosuvastatin. If interstitial lung disease is suspected, therapy with Rosucard® should be discontinued.

When studying the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was noted in representatives of the Mongoloid race. This fact should be taken into account when prescribing Rosucard® to patients of the Mongoloid race.

Impact on the ability to drive vehicles and operate machinery

Patients should be careful when driving vehicles and doing activities that require increased concentration and speed of psychomotor reactions (dizziness may occur during therapy).

Rozucard®

Effect of the use of other drugs on rosuvastatin
Transport protein inhibitors:

rosuvastatin binds to some transport proteins, in particular OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of developing myopathy (see Table 3 and sections “Dosage and Administration” and “Special Instructions”).

Cyclosporine:

with simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers (see Table 3). Does not affect plasma concentrations of cyclosporine. Rosucard® is contraindicated in patients taking cyclosporine (see section "Contraindications").

Human immunodeficiency virus (HIV) protease inhibitors:

Although the exact mechanism of interaction is unknown, coadministration of HIV protease inhibitors may result in a significant increase in rosuvastatin exposure (see Table 3). A pharmacokinetic study of the simultaneous use of 20 mg rosuvastatin with a combination drug containing two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in an approximately two-fold and five-fold increase in AUC(o_24) and Cmax of rosuvastatin, respectively. Therefore, simultaneous use of the drug Rosucard® and HIV protease inhibitors is not recommended (see sections “Method of administration and dosage”, “Special instructions”, table 3).

Gemfibrozil and other lipid-lowering drugs:

The combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in the Cmax and AUC of rosuvastatin (see section “Special Instructions”). Based on specific interaction data, a pharmacokinetically significant interaction with fenofibrate is not expected; a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g per day) increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy (see . section "Special instructions"). When taking the drug simultaneously with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses, patients are recommended to take an initial dose of Rosucard® 5 mg; taking a dose of 40 mg is contraindicated when co-administered with fibrates (see sections “Contraindications”, “Dosage and Administration”, "Special instructions").

Fusidic acid:

There have been no specific drug interaction studies between fusidic acid and rosuvastatin, but isolated case reports of rhabdomyolysis have been noted.

Ezetimibe:

simultaneous use of Rosucard® at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see Table 3). An increased risk of side effects due to the pharmacodynamic interaction between Rosucard® and ezetimibe cannot be excluded.

Antacids:

simultaneous use of rosuvastatin and antacid suspensions containing magnesium and aluminum hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin:

simultaneous use of rosuvastatin and erythromycin leads to a decrease in AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by erythromycin.

Isoenzymes of the cytochrome P450 system:

in vivo
and
in vitro
studies showed that rosuvastatin is neither an inhibitor nor an inducer of isoenzymes of the cytochrome P450 system. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, interaction of rosuvastatin with other drugs at the metabolic level involving isoenzymes of the cytochrome P450 system is not expected. There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 and CYP3A4 isoenzymes).

Interactions with drugs that require dose adjustment of rosuvastatin (see Table 3)

The dose of Rosucard® should be adjusted if it is necessary to use it together with drugs that increase the exposure of rosuvastatin. If an increase in exposure by 2 times or more is expected, the initial dose of Rosucard® should be 5 mg once daily. The maximum daily dose of Rosucard® should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs that interact with rosuvastatin. For example, the maximum daily dose of Rosucard® when used simultaneously with gemfibrozil is 20 mg (increased exposure by 1.9 times), with ritonavir/atazanavir - 10 mg (increased exposure by 3.1 times).

Table 3. Effect of concomitant therapy on rosuvastatin exposure (AUC, data in descending order) - results from published clinical studies.

The effect of rosuvastatin on other drugs.

Vitamin K antagonists:

Initiating therapy or increasing the dose of Rosucard® in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in the International Normalized Ratio (INR). Discontinuation or reduction of the dose of Rosucard® may lead to a decrease in the INR. In such cases, INR monitoring is recommended.

Oral contraceptives/hormone replacement therapy:

simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. This increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. There are no pharmacokinetic data on the simultaneous use of Rosucard® and hormone replacement therapy; therefore, a similar effect cannot be excluded when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medicines:

No clinically significant interaction between rosuvastatin and digoxin is expected.