Rosucard, 10 mg 30 pcs

Rosucard is a hypolipidemic drug from the group of statins. It is a selective competitive inhibitor of Z-hydroxy-Z-methylglutaryl coenzyme A (HMG-CoA)-reductase – the enzyme that converts HMG-CoA into mevalonate, a precursor of cholesterol (CH).

Lincreases the number of low-density lipoprotein (LDL) receptors on the surface of hepatocytes, which leads to increased capture and catabolism of LDL, inhibiting the synthesis of very low-density lipoprotein (VLDL), reducing the total concentration of LDL and VLDL. Reduces concentrations of CH-LDL, high-density cholesterol-non-lipoproteins (HDL-C), LDL-C, total CH, triglycerides (TG), TG-LDL-C, apolipoprotein B (ApoB), decreases the ratios of CH-LDL/HC-LDL, total CH/CH-LDL, non-HC-LDL/HC-LDL, apoB/apolipoprotein A-1 (apoA-I), increases concentrations of CH-LDL and apoA-I.

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

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 of IIa and IIb types (classification according to Fredrickson) with baseline mean concentration of CH-LDL about 4.8 mmol / L against the drug administration in a dose of 10 mg, HC-LDL concentration reaches values less than 3 mmol / L. In patients with homozygous familial hypercholesterolemia taking the drug in doses of 20 mg and 40 mg the mean decrease of LDL-C concentration is 22%.

Additive effect is noted in combination with fenofibrate (in regard to decrease of TG concentration and with nicotinic acid in lipid-lowering doses (at least 1 g/day) (in regard to decrease of HDL-C concentration).

Indications

Active ingredient

Composition

1 tablet – calcium rosuvastatin 10.4 mg, which corresponds to the content of rosuvastatin 10 mg.

Excipients:

Lactose monohydrate – 60 mg,

Microcrystalline cellulose – 45.4 mg,

croscarmellose sodium – 1.2 mg,

colloidal silicon dioxide – 600 µg,

magnesium stearate – 2.4 mg.

Content of film coating:

Hypromellose 2910/5 – 2.5 mg, macrogol 6000 – 400 µg, titanium dioxide – 325 µg, talc – 475 µg, iron oxide red dye – 13 µg.

How to take, the dosage

Orally, without chewing or crushing, swallow it whole with water at any time of day regardless of meals.

Before starting therapy with ROSUKARD® the patient should start a standard hypolipidemic diet and continue it during treatment. The drug dose 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 in a dose of 5 mg, the 10 mg tablet should be divided into two parts by risk.

The recommended starting dose of ROSUKARD® for patients starting to take the drug or for patients switching from other HMG-CoA reductase inhibitors is 5 or 10 mg once daily. When choosing the initial dose, the patient’s cholesterol content should be guided and the risk of cardiovascular complications should be taken into account, and the potential risk of side effects should be assessed. If necessary, the drug dose may be increased after 4 weeks.

With regard to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug (see “Side effects of the drug”).

Particularly in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia) who will be under medical supervision and whose target cholesterol levels were not achieved with the 20 mg dose, final titration to a maximum dose of 40 mg should only be performed.

Patients with hepatic impairment

In patients with hepatic impairment with Child-Pugh scores below 7, no dose adjustment of ROSUKARD® is necessary.

Patients with renal impairment

In patients with mild renal impairment, no dose adjustment is required. The recommended starting dose of ROSUKARD® is 5 mg per day.

In patients with severe renal insufficiency (CKD less than 30 ml/min) the use of ROSUKARD® is contraindicated.
In patients with moderate renal insufficiency (CKD 30-60 ml/min) the use of ROSUKARD® in dose of 40 mg per day is contraindicated.

Particular populations. Elderly patients

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

Patients with predisposition to myopathy

The use of ROSUCARD® at a dose of 40 mg daily is contraindicated in patients with predisposition to myopathy. When doses of 10 mg and 20 mg daily are prescribed, the recommended starting dose of ROSUCARD® for this group of patients is 5 mg daily.

Ethnic groups

When studying pharmacokinetic parameters of rosuvastatin an increase in systemic drug concentration was noted in persons of mongoloid race. This fact should be considered when prescribing ROSUCARD® to patients of mongoloid race.

In doses of 10 and 20 mg the recommended initial dose of ROSUKARD® for this group of patients is 5 mg daily. ROSUKARD® is contraindicated in mongoloid races at a dose of 40 mg daily.

When prescribing ROSUKARD® with gemfibrozil, the dose should not exceed 10 mg daily.

Interaction

Concomitant use of rosuvastatin and cyclosporine has no effect on plasma concentration of cyclosporine, but the effect of rosuvastatin is enhanced (its excretion slows down, AUC increases 7-fold, Cmax increases 11-fold).
Erythromycin increases bowel motility, which leads to decreased effect of rosuvastatin (AUC decreases by 20% and Cmax by 30%).

In patients receiving vitamin K antagonists (e.g., warfarin) monitoring of international normalized ratio (INR) is recommended because initiation of rosuvastatin therapy or increasing the dose of the drug may increase INR, and discontinuation of rosuvastatin or reducing its dose may decrease it. Gemfibrozil enhances the effect of rosuvastatin (increases Cmax and AUC by 2-fold). Concomitant use of rosuvastatin and antacids containing aluminum and magnesium hydroxide leads to a decrease in plasma concentration of rosuvastatin by about 50%. This effect is weaker if antacids are used 2 h after taking rosuvastatin.

The concomitant use of rosuvastatin and oral contraceptives increases AUC of ethinylestradiol and AUC of nogestrel by 26% and 34%, respectively, which should be considered when choosing a dose of oral contraceptives. There are no pharmacokinetic data on concomitant use of rosuvastatin and hormone replacement therapy; therefore, a similar effect cannot be excluded when using this combination.

The results of studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Rosuvastatin is a non-core substrate for these isoenzymes. No clinically significant interactions have been observed with drugs such as fluconazole, ketoconazole and itraconazole, which are metabolized with the cytochrome P450 system.

There were no clinically significant interactions of rosuvastatin with digoxin or pheno-fibrate, Hemfibrozil, other fibrates and hypolipidemic doses of nicotinic acid (at least 1 g/day) increased the risk of myopathy when concomitantly used with other HMG-CoA reductase inhibitors. It is possible due to the fact that they can also cause myopathy when used as monotherapy.

The co-administration of rosuvastatin and ezetimibe did not result in changes in AUC or Cmax of both drugs.

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

Special Instructions

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

It is recommended that liver function tests be performed before therapy and 3 months after the start of therapy. Rosecard® should be discontinued or the dose should be reduced if the serum hepatic transaminase activity is 3 times greater than BHF.

When using Rosucard® at a dose of 40 mg, it is recommended to monitor renal function parameters.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy for underlying disease should be performed before starting treatment with Rosucard®.

In patients with existing risk factors for rhabdomyolysis, the ratio of expected benefit to potential risk should be considered and clinical monitoring should be conducted throughout the course of treatment.

Patients should be informed to immediately inform their physician if they experience muscle pain, muscle weakness, or cramping, especially if combined 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 that of IGN) or muscle symptoms are severe and cause daily discomfort. If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Rosecard® or other HMG-CoA reductase inhibitors at lower doses with close monitoring of the patient.

The determination of CPK activity should not be performed after vigorous physical activity or in the presence of other possible causes of its increase, which may lead to misinterpretation of the results. If the baseline CPK activity is significantly elevated, repeat measurement after 5-7 days – therapy should not be started if the repeat test confirms the baseline CPK activity (5 times higher than normal).

Routine monitoring of CPK activity in the absence of the symptoms described above is inappropriate.

A higher incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrates (including gemfibrozil), cyclosporine, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. The ratio of expected benefit to potential risk should be carefully weighed in coadministration of Rosecard® and fibrates or nicotinic acid (in lipid-lowering doses – 1 g/day), concomitant 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 renal disease. Assessment of renal function should be performed during routine evaluation of patients receiving a dose of 40 mg.

The statin class of drugs has the potential to cause elevated blood glucose concentrations. In some patients with high risk of developing diabetes mellitus such changes may lead to its manifestation, which is an indication for prescription of hypoglycemic therapy. However, the reduction in the risk of vascular disease on the background of statins exceeds the risk of diabetes mellitus, so this factor should not be a reason for withdrawal of treatment with statins. Patients in risk group (fasting blood glucose concentration 5,6-6,9 mmol/l, BMI >30 kg/m2, hypertriglyceridemia, arterial hypertension in anamnesis) should be under medical supervision and biochemical parameters should be controlled regularly.

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

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

When studying pharmacokinetic parameters of rosuvastatin an increase in systemic drug concentration has been noted in mongoloid race (see “Pharmacokinetics”). This fact should be considered when prescribing Rosucard® to these patients.

Impact on the ability to drive vehicles and operate machinery. Caution should be exercised while driving motor transport and doing activities requiring high concentration and quick psychomotor reactions (dizziness may occur during the therapy).

Contraindications

Side effects

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

The digestive system: frequent – nausea, constipation, abdominal pain; infrequent – vomiting; rare – pancreatitis; very rare – hepatitis, jaundice; unspecified frequency – diarrhea.

Respiratory system: infrequent – cough, dyspnea.

Endocrine system: frequently – diabetes mellitus type 2.

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

Allergic reactions: infrequent – skin itching, urticaria, rash, rarely – angioedema.

Skin and subcutaneous tissue: unspecified frequency – Stevens-Johnson syndrome, peripheral edema.

Survivors of the urinary system: frequent – proteinuria (with a frequency of more than 3% in patients receiving a dose of 40 mg), decreasing with therapy and not associated with the occurrence of renal disease, urinary tract infection; very rare – hematuria.

Laboratory parameters: infrequent transient dose-dependent increase of serum creatine phosphokinase (CPK) activity; with increase of more than 5 times the upper limit of normal, therapy should be temporarily suspended; rare – transient increase of aspartataminotransferase and alanine aminotransferase activity.

As with other HMG-CoA reductase inhibitors, the incidence is dose-dependent; side effects are usually mild and self-limited.

When using ROSUKARD® changes in the following laboratory parameters were noted: increase of glucose concentration, bilirubin, alkaline phosphatase activity, gamma-glutamyltransferase.
The following side effects were reported with other statins: depression, insomnia, decreased potency.

In long-term use of rosuvastatin, single cases of interstitial lung disease have been reported.

Overdose

The pharmacokinetic parameters of rosuvastatin do not change when multiple daily doses are administered simultaneously.

Treatment: There is no specific treatment; symptomatic therapy to maintain the functions of vital organs and systems is provided.

Liver function parameters and CPK activity should be monitored. Hemodialysis is ineffective.

Pregnancy use

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

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