Rosistark tablets p / o 10mg, No. 70

Hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other non-drug treatments (eg, exercise, weight loss) are insufficient.

Familial homozygous hypercholesterolemia as an adjunct to diet and other cholesterol-lowering therapy or when such therapy is not suitable for the patient.

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

It is taken internally. The recommended starting dose is 10 mg once a day. If necessary, the dose can be increased to 20 mg after 4 weeks. Increasing the dose to 40 mg is possible only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) with insufficient efficacy at a dose of 20 mg and subject to medical supervision.

Active ingredient: rosuvastatin calcium - 10.4 mg, which corresponds to the content of rosuvastatin - 10 mg

Excipients : lactose monohydrate - 89.64 mg, microcrystalline cellulose - 42.685 mg, crospovidone - 6 mg, magnesium stearate - 1.275 mg.

Shell composition: lactose monohydrate - 1.8 mg, hypromellose - 1.26 mg, titanium dioxide - 1.0778 mg, triacetin - 0.36 mg, quinoline yellow - 0.0022 mg.

Liver disease in the active phase (including a persistent increase in the activity of hepatic transaminases or any increase in the activity of transaminases by more than 3 times compared with VGN), severe renal dysfunction (CC <30 ml / min), myopathy, concomitant use of cyclosporine, pregnancy, lactation (breastfeeding), women of reproductive age who do not use adequate methods of contraception, children and adolescents under 18 years of age, hypersensitivity to rosuvastatin.

Light yellow to yellow film-coated tablets, round, biconvex, engraved with '10' on one side and '15' on the other side.

Composition:

Active ingredient: rosuvastatin calcium - 10.4 mg, which corresponds to the content of rosuvastatin - 10 mg

Excipients : lactose monohydrate - 89.64 mg, microcrystalline cellulose - 42.685 mg, crospovidone - 6 mg, magnesium stearate - 1.275 mg.

Shell composition: lactose monohydrate - 1.8 mg, hypromellose - 1.26 mg, titanium dioxide - 1.0778 mg, triacetin - 0.36 mg, quinoline yellow - 0.0022 mg.

Clinical and pharmacological group: Lipid-lowering drug

Pharmaco-therapeutic group: Lipid-lowering agent - HMG-CoA reductase inhibitor

pharmachologic effect

Lipid-lowering agent from the group of statins, inhibitor of HMG-CoA reductase. According to the principle of competitive antagonism, the statin molecule binds to the part of the coenzyme A receptor where this enzyme attaches. Another part of the statin molecule inhibits the conversion of hydroxymethylglutarate to mevalonate, an intermediate in the synthesis of the cholesterol molecule. Inhibition of the activity of HMG-CoA reductase leads to a series of sequential reactions resulting in a decrease in the intracellular cholesterol content and a compensatory increase in the activity of LDL receptors and, accordingly, an acceleration of the catabolism of LDL cholesterol (Xc).

The lipid-lowering effect of statins is associated with a decrease in the level of total cholesterol due to LDL cholesterol. The decrease in LDL cholesterol is dose-dependent and not linear, but exponential.

Statins do not affect the activity of lipoprotein and hepatic lipases, do not have a significant effect on the synthesis and catabolism of free fatty acids, therefore their effect on the TG level is secondary and is mediated through their main effects on lowering the level of LDL-C. A moderate decrease in the level of TG during treatment with statins, apparently, is associated with the expression of remnant (apo E) receptors on the surface of hepatocytes involved in the catabolism of DID, which comprise about 30% TG.

In addition to the hypolipidemic effect, statins have a positive effect on endothelial dysfunction (a preclinical sign of early atherosclerosis), on the vascular wall, the state of atheroma, improve the rheological properties of blood, have antioxidant, antiproliferative properties.

The therapeutic effect appears within 1 week. after the start of therapy and after 2 weeks of treatment, it is 90% of the maximum possible effect, which is usually achieved by 4 weeks and after that remains constant.

Pharmacokinetics

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

Rosuvastatin accumulates in the liver. Vd - about 134 liters. Plasma protein binding (mainly albumin) is approximately 90%.

It is biotransformed to a small extent (about 10%), being a non-core substrate for isoenzymes of the cytochrome P450 system. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. Isoenzymes CYP2C19, CYP3A4 and CYP2D6 are involved in metabolism to a lesser extent.

The main identified metabolites of rosuvastatin are N-dismethyl and lactone metabolites. N-dismethyl is approximately 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive.

About 90% of the dose of rosuvastatin is excreted unchanged in the feces. The remainder is excreted in the urine. Plasma T1 / 2 - about 19 hours T1 / 2 does not change with increasing dose. The average plasma clearance is approximately 50 L / h (coefficient of variation 21.7%).

As in the case of other HMG-CoA reductase inhibitors, the membrane transporter Xc is involved in the process of hepatic uptake of rosuvastatin, which plays an important role in the hepatic elimination of rosuvastatin.

The systemic exposure of rosuvastatin increases in proportion to the dose.

In patients with severe renal failure (CC <30 ml / min), the concentration of rosuvastatin in the blood plasma is 3 times higher, and the concentration of N-dismethyl is 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in hemodialysis patients was approximately 50% higher than in healthy volunteers.

In patients with liver failure, the degree of which was 8 and 9 on the Childe-Pugh scale, an increase in T1 / 2 was noted at least 2 times.

Indications

Hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other non-drug treatments (eg, exercise, weight loss) are insufficient.

Familial homozygous hypercholesterolemia as an adjunct to diet and other cholesterol-lowering therapy or when such therapy is not suitable for the patient.

Dosage regimen

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

It is taken internally. The recommended starting dose is 10 mg once a day. If necessary, the dose can be increased to 20 mg after 4 weeks. Increasing the dose to 40 mg is possible only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) with insufficient efficacy at a dose of 20 mg and subject to medical supervision.

Side effect

From the side of the central nervous system: often - headache, dizziness, asthenic syndrome; possibly - anxiety, depression, insomnia, neuralgia, paresthesia.

From the digestive system: often - constipation, nausea, abdominal pain; possible - a reversible transient dose-dependent increase in the activity of hepatic transaminases, dyspepsia (including diarrhea, flatulence, vomiting), gastritis, gastroenteritis.

From the respiratory system : often - pharyngitis; possibly - rhinitis, sinusitis, bronchial asthma, bronchitis, cough, dyspnea, pneumonia.

From the side of the cardiovascular system: possibly - angina pectoris, increased blood pressure, palpitations, vasodilation.

From the musculoskeletal system: often - myalgia; possible - arthralgia, arthritis, muscle hypertonia, back pain, pathological pearl of the limb (without damage); rarely - myopathy, rhabdomyolysis (simultaneously with impaired renal function, while taking the drug at a dose of 40 mg).

From the urinary system: tubular proteinuria (in less than 1% of cases - for doses of 10 and 20 mg, 3% of cases - for a dose of 40 mg); possibly - peripheral edema (arms, legs, ankles, legs), lower abdominal pain, urinary tract infections.

Allergic reactions: possible - skin rash, itching; rarely - angioedema.

On the part of laboratory parameters: a transient dose-dependent increase in CPK activity (with an increase in CPK activity more than 5 times compared with VGN, therapy should be temporarily suspended).

Others: often - asthenic syndrome; possibly accidental trauma, anemia, chest pain, diabetes mellitus, ecchymosis, flu-like syndrome, periodontal abscess.

Contraindications for use

Liver disease in the active phase (including a persistent increase in the activity of hepatic transaminases or any increase in the activity of transaminases by more than 3 times compared with VGN), severe renal dysfunction (CC <30 ml / min), myopathy, concomitant use of cyclosporine, pregnancy, lactation (breastfeeding), women of reproductive age who do not use adequate methods of contraception, children and adolescents under 18 years of age, hypersensitivity to rosuvastatin.

Application during pregnancy and lactation

Contraindicated during pregnancy and lactation.

Do not use in women of reproductive age who do not use reliable methods of contraception.

Application for violations of liver function

Contraindicated in liver diseases in the active phase (including a persistent increase in the activity of hepatic transaminases or any increase in the activity of transaminases by more than 3 times compared with VGN).

Application for impaired renal function

Contraindicated in severe renal impairment (CC <30 ml / min).

Application in children

Contraindicated in children and adolescents under 18 years of age (since efficacy and safety have not been established).

special instructions

Use with caution in the presence of risk factors for the development of rhabdomyolysis (including renal failure, hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates), in chronic alcoholism, in patients older than 65 years old, with a history of liver disease, sepsis, arterial hypotension, during major surgical interventions, trauma, severe metabolic endocrine or electrolyte disturbances, with uncontrolled epilepsy, in people of Asian origin (Chinese, Japanese).

Therapy should be discontinued if the CPK level is significantly increased (more than 5 times compared to VGN) or if muscle symptoms are pronounced and cause daily discomfort (even if the CPK level is 5 times less than VGN).

When using rosuvastatin at a dose of 40 mg, it is recommended to monitor the indicators of renal function.

In most cases, proteinuria diminishes or disappears with therapy and does not mean acute or progression of existing kidney disease.

An increase in the incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Thus, the simultaneous administration of rosuvastatin and gemfibrozil is not recommended. The balance of risk and potential benefit should be carefully weighed when rosuvastatin and fibrates or niacin are used together.

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

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy for the underlying diseases should be carried out before starting treatment with rosuvastatin.

Influence on the ability to drive vehicles and use mechanisms

When engaging in potentially hazardous activities, patients should be aware that dizziness may occur during therapy.

Drug interactions

With the simultaneous use of rosuvastatin and cyclosporin, the AUC of rosuvastatin was on average 7 times higher than the value that was observed in healthy volunteers, the plasma concentration of cyclosporin did not change.

Initiation of rosuvastatin therapy or an increase in the dose of the drug in patients receiving concomitantly vitamin K antagonists (for example, warfarin) can lead to an increase in prothrombin time and INR, and withdrawal of rosuvastatin or dose reduction may lead to a decrease in INR (in such cases, monitoring of INR is recommended).

The combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in plasma Cmax and AUC of rosuvastatin.

The simultaneous use of rosuvastatin and antacids containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin (clinical significance is unknown).

The simultaneous use of rosuvastatin and erythromycin leads to a decrease in the AUC of rosuvastatin by 20% and the Cmax of rosuvastatin by 30% (probably as a result of increased intestinal motility caused by the intake of erythromycin).

The simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and the AUC of norgestrel by 26% and 34%, respectively. Such an interaction cannot be excluded with the simultaneous use of rosuvastatin and hormone replacement therapy.

Gemfibrozil, other fibrates, and hypolipidemic doses of nicotinic acid (? 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 itraconazole (a CYP3A4 inhibitor) increases the AUC of rosuvastatin by 28% (clinically insignificant).