Rosucard, 20 mg 30 pcs

Hypolipidemic drug from the group of statins. Selective competitive inhibitor of HMG-CoA reductase – the enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol (Chs).

increases the number of LDL receptors on the surface of hepatocytes, which leads to increased capture and catabolism of LDL, inhibiting LDL synthesis, reducing the total concentration of LDL and LDL-LDL. Reduces concentrations of Chs-LDL, high-density non-lipoprotein cholesterol (HDL-C), Chs-LDL, total Chs, TG, TG-LDL, apolipoprotein B (ApoB), decreases the ratios of Chs-LDL/Hs-LDL, total Chs/Hs-LDL, Chs-non-LDL/Hs-LDL, ApoB/apolipoprotein A-1 (ApoA-1), increases concentrations of Chs-LDL and ApoA-1.

The hypolipidemic effect is directly proportional to the dose prescribed. The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks it reaches 90% of the maximum, by 4 weeks it reaches its maximum and after that it remains constant.

Clinical efficacy

It is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, sex or age, including patients with diabetes and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia type IIa and IIb (according to Fredrickson classification) with baseline mean concentration of chs-LDL about 4.8 mmol/L after the use of 10 mg the concentration of chs-LDL reached values less than 3 mmol/L.

In patients with heterozygous familial hypercholesterolemia receiving rosuvastatin at a dose of 20-80 mg/day, positive dynamics of lipid profile parameters are observed. After titration to a daily dose of 40 mg (12 weeks of therapy), there was a 53% decrease in LDL-C concentration. In 33% of patients the concentration of LDL-C less than 3 mmol/l was achieved.

In patients with homozygous familial hypercholesterolemia receiving rosuvastatin at a dose of 20 mg and 40 mg, the mean decrease in LDL-C concentration was 22%.

In patients with hypertriglyceridemia with an initial TG concentration of 273 mg/dL to 817 mg/dL who received rosuvastatin in doses of 5 mg to 40 mg once daily for 6 weeks, plasma TG concentrations were significantly reduced (see Table 2).

Additive effect was observed in combination with fenofibrate with respect to TG concentration and with nicotinic acid at lipid-lowering doses (more than 1 g/day) with respect to HDL-C concentration.

In the METEOR study, rosuvastatin therapy significantly slowed the rate of progression of maximum intima-media complex (IMC) thickness for 12 carotid segments compared with placebo. Compared with baseline values, the rosuvastatin group showed a 0.0014 mm/year decrease in maximal SCIM compared with a 0.0131 mm/year increase in the placebo group. To date, no direct correlation between the reduction in SCIM and the reduction in the risk of cardiovascular events has been demonstrated.

The results of the JUPITER study showed that rosuvastatin significantly reduced the risk of cardiovascular complications with a relative risk reduction of 44%. The efficacy of therapy was noted after the first 6 months of use of the drug. There was a statistically significant 48% reduction in the combined criterion, which included death from cardiovascular causes, stroke and myocardial infarction, a 54% reduction in the incidence of fatal or nonfatal myocardial infarction, and a 48% reduction in the incidence of fatal or nonfatal stroke. Overall mortality was reduced by 20% in the rosuvastatin group. The safety profile in patients taking rosuvastatin at a dose of 20 mg was generally similar to the safety profile in the placebo group.

Indications

Primary hypercholesterolemia (type IIa according to Fredrickson), including heterozygous hereditary hypercholesterolemia or mixed (combined) hypercholesterolemia (type IIb according to Fredrickson), as an addition to diet and other non-drug measures (physical activity and weight loss) when diet therapy and non-drug measures are ineffective;
Homozygous form of hereditary hypercholesterolemia and when diet therapy and other treatments aimed at lowering lipid levels (eg, LDL apheresis) are insufficiently effective, or if such treatments are not suitable for the patient.
Hypertriglyceridemia (Fredrickson type IV) as an adjunct to diet.
To slow the progression of atherosclerosis as an addition to diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL cholesterol.
Prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), but with an increased risk of its development (age over 50 years for men and over 60 years for women, increased concentration of C-reactive protein (≥ 2 mg/l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low HDL-C concentration, smoking, family history of early onset ischemic heart disease).

Pharmacological effect

A lipid-lowering drug from the statin group. A selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts HMG-CoA into mevalonate, a precursor of cholesterol (Cc).

Increases the number of LDL receptors on the surface of hepatocytes, which leads to increased uptake and catabolism of LDL, inhibition of VLDL synthesis, reducing the total concentration of LDL and VLDL. Reduces the concentrations of LDL-C, high-density non-lipoprotein cholesterol (non-HDL-C), VLDL-C, total cholesterol, TG, VLDL-TG, apolipoprotein B (ApoB), reduces the LDL-C/HDL-C ratio, total cholesterol/HDL-C, non-HDL-C/HDL-C, ApoB/apolipoprotein A-1 (ApoA-1), increases the concentrations of HDL-C and ApoA-1.

The lipid-lowering effect is directly proportional to the prescribed dose. The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks it reaches 90% of the maximum, by 4 weeks it reaches a maximum and after that remains constant.

Clinical effectiveness

Effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender or age, incl. in patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia type IIa and IIb (according to the Fredrickson classification) with an average initial LDL-C concentration of about 4.8 mmol/l, while taking the drug at a dose of 10 mg, the LDL-C concentration reaches values ​​of less than 3 mmol/l.

In patients with heterozygous familial hypercholesterolemia receiving rosuvastatin at a dose of 20-80 mg/day, positive dynamics of lipid profile indicators are noted. After titration to a daily dose of 40 mg (12 weeks of therapy), a decrease in LDL-C concentrations of 53% was noted. In 33% of patients, an LDL-C concentration of less than 3 mmol/l was achieved.

In patients with homozygous familial hypercholesterolemia receiving rosuvastatin 20 mg and 40 mg, the average reduction in LDL-C concentration was 22%.

In patients with hypertriglyceridemia with an initial TG concentration of 273 mg/dL to 817 mg/dL, who received rosuvastatin in doses of 5 mg to 40 mg 1 time/day for 6 weeks, the concentration of TG in the blood plasma significantly decreased (see Table 2).

An additive effect is observed in combination with fenofibrate in relation to the concentration of TG and with nicotinic acid in lipid-lowering doses (more than 1 g/day) in relation to the concentration of HDL-C.

In the METEOR study, rosuvastatin treatment significantly slowed the rate of progression of maximum intima-media thickness (IMT) for 12 carotid artery segments compared with placebo. Compared to baseline values, a decrease in the maximum IMT value of 0.0014 mm/year was noted in the rosuvastatin group compared with an increase of 0.0131 mm/year in the placebo group. To date, a direct relationship between a decrease in IMT and a decrease in the risk of cardiovascular events has not been demonstrated.

The results of the JUPITER study showed that rosuvastatin significantly reduced the risk of cardiovascular complications with a relative risk reduction of 44%. The effectiveness of therapy was noted after the first 6 months of using the drug. There was a statistically significant reduction of 48% in the combined criterion, which included death from cardiovascular causes, stroke and myocardial infarction, a 54% reduction in the occurrence of fatal or non-fatal myocardial infarction and a 48% reduction in fatal or non-fatal stroke. Overall mortality decreased by 20% in the rosuvastatin group. The safety profile in patients receiving rosuvastatin 20 mg was generally similar to that in the placebo group.

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. Taking Rosucard® should be stopped 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 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 of the need to immediately report to the doctor if muscle pain, muscle weakness or cramps occur, 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 muscle symptoms are severe and cause daily discomfort. If symptoms disappear and CPK activity returns to normal, 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 its increase, which may lead to incorrect interpretation of the results obtained. If the initial CPK activity is significantly increased, a repeat measurement should be taken after 5-7 days; therapy cannot 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 the above-described 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® together with fibrates or nicotinic acid (in lipid-lowering doses – 1 g / day); simultaneous 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 assessment of patients receiving the 40 mg dose.

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 the administration of hypoglycemic therapy. However, the reduction in the risk of vascular diseases while taking statins exceeds the risk of developing diabetes, so this factor should not serve as a basis for discontinuing statin treatment. Patients at risk (fasting blood glucose concentration 5.6–6.9 mmol/l, BMI >30 kg/m2, hypertriglyceridemia, history of arterial hypertension) should be under medical supervision and regularly monitor biochemical parameters.

Co-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 (see “Pharmacokinetics”). This fact should be taken into account when prescribing the drug Rosucard® to these patients.

Impact on the ability to drive vehicles and operate machinery. Caution should be exercised when driving vehicles and doing activities that require increased concentration and speed of psychomotor reactions (dizziness may occur during therapy).

Active ingredient

Rosuvastatin

Composition

1 tab. – rosuvastatin calcium 20.8 mg, which corresponds to the content of rosuvastatin 20 mg.

Excipients:

lactose monohydrate – 120 mg,

microcrystalline cellulose – 90.8 mg,

croscarmellose sodium – 2.4 mg,

colloidal silicon dioxide – 1.2 mg,

magnesium stearate – 4.8 mg.

Film shell composition:

hypromellose 2910/5 – 5 mg, macrogol 6000 – 800 mcg, titanium dioxide – 650 mcg, talc – 950 mcg, red iron oxide dye – 65 mcg.

Pregnancy

The drug is contraindicated during pregnancy, lactation and under the age of 18 years

Contraindications

Hypersensitivity;
Liver disease in the active phase or a sustained increase in serum activity of “liver” transaminases (more than 3 times compared to the upper limit of normal) of unknown origin, liver failure (severity from 7 to 9 points on the Child-Pugh scale);
An increase in the concentration of creatinine phosphokinase (CPK) in the blood by more than 5 times compared to the upper limit of normal (ULN);
Hereditary diseases such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption (due to the presence of lactose);
Severe renal dysfunction (creatinine clearance less than 30 ml/min);
Myopathy;
Patients predisposed to the development of myotoxic complications;
Concomitant use of cyclosporine;
Combined use with HIV protease inhibitors;
Women of reproductive age who do not use adequate methods of contraception.

Side Effects

From the central nervous system: often – headache, dizziness, asthenic syndrome; very rarely – peripheral neuropathy, memory loss.

From the digestive system: often – nausea, constipation, abdominal pain; infrequently – vomiting; rarely – pancreatitis; very rarely – hepatitis, jaundice; unspecified frequency – diarrhea.

From the respiratory system: infrequently – cough, dyspnea.

From the endocrine system: often – type 2 diabetes mellitus.

From the musculoskeletal system: often – myalgia; very rarely – arthralgia; rarely – myopathy (including myositis), rhabdomyolysis.

Allergic reactions: uncommon – itching, urticaria, rash; rarely – angioedema.

Skin and subcutaneous tissue: frequency not specified – Stevens-Johnson syndrome, peripheral edema.

From the urinary system: often – proteinuria (with a frequency of more than 3% in patients receiving a dose of 40 mg), decreasing during therapy and not associated with the occurrence of kidney disease, urinary tract infections; very rarely – hematuria.

Laboratory indicators: infrequently – a transient dose-dependent increase in the activity of serum creatine phosphokinase (CPK), with an increase of more than 5 times compared to the upper limit of normal, therapy should be temporarily suspended; rarely – transient increase in the activity of aspartate aminotransferase and alanine aminotransferase.

As with the use of other HMG-CoA reductase inhibitors, the incidence is dose-dependent, side effects are usually mild and go away on their own.

When using ROZUKARD®, changes in the following laboratory parameters were observed: increased concentrations of glucose, bilirubin, alkaline phosphatase activity, gamma-glutamyltransferase.
The following side effects have been reported with other statins: depression, insomnia, decreased potency.

Isolated cases of interstitial lung disease have been reported with long-term use of rosuvastatin.

Interaction

The simultaneous use of rosuvastatin and cyclosporine does not affect the plasma concentration of cyclosporine, however, the effect of rosuvastatin is enhanced (its elimination slows down, AUC increases by 7 times, Cmax increases by 11 times).

Erythromycin increases intestinal motility, which leads to a decrease in the effect of rosuvastatin (AUC decreases by 20% and Cmax by 30%).

In patients receiving vitamin K antagonists (eg, warfarin), monitoring of the international normalized ratio (INR) is recommended, since initiating rosuvastatin therapy or increasing the dose of the drug may lead to an increase in the INR, and discontinuation of rosuvastatin or reducing its dose may lead to a decrease. Gemfibrozil enhances the effect of rosuvastatin (increases Cmax and AUC by 2 times). The simultaneous use of rosuvastatin and antacids containing aluminum and magnesium 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 simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively, which should be taken into account when selecting the dose of oral contraceptives. There are no pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy; therefore, a similar effect cannot be excluded when using this combination.

The research results showed that rosuvastatin is neither an inhibitor nor an inducer of the action of cytochrome P450 isoenzymes. Rosuvastatin is a non-core substrate for these isoenzymes. No clinically significant interactions were observed with drugs such as fluconazole, ketoconazole and itraconazole, which are metabolized by the cytochrome P450 system.
There is no clinically significant interaction of rosuvastatin with digoxin or fenofibrate; Gemfibrozil, other fibrates and lipid-lowering doses of nicotinic acid (at least 1 g/day) increased the risk of myopathy when used simultaneously with other HMG-CoA reductase inhibitors. Possibly due to the fact that they can cause myopathy when used as monotherapy.

The combined use of rosuvastatin and ezetimibe did not lead to changes in the AUC or Cmax of both drugs.
The use of HIV (human immunodeficiency virus) protease inhibitors with rosuvastatin can lead to a significant increase in the effect of rosuvastatin. A pharmacokinetic study of co-administration of 20 mg rosuvastatin and a combination of two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in approximately two- and five-fold increases in AUC(0-24) and Cmax, respectively. Therefore, co-administration of rosuvastatin with HIV protease inhibitors is not recommended in patients infected with HIV.

Overdose

When taking several daily doses simultaneously, the pharmacokinetic parameters of rosuvastatin do not change.

Treatment: there is no specific treatment; symptomatic therapy is carried out to maintain the functions of vital organs and systems. Monitoring of liver function indicators and CPK activity is necessary. Hemodialysis is ineffective.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

2 years

Manufacturer

Zentiva k.s., Czech Republic