Rosistarck, 40 mg 28 pcs.

Hypolipidemic drug from the group of statins, HMG-CoA reductase inhibitor. By the principle of competitive antagonism, statin molecule binds to the part of coenzyme A receptor, where this enzyme is attached. The other part of the statin molecule inhibits the conversion of hydroxymethylglutarate into mevalonate, an intermediate product in the synthesis of the cholesterol molecule. Inhibition of HMG-CoA reductase activity leads to a series of sequential reactions resulting in a decrease of intracellular cholesterol content and a compensatory increase of LDL-receptor activity and corresponding acceleration of LDL cholesterol (Xc) catabolism.

The hypolipidemic effect of statins is associated with a decrease in total Xc levels at the expense of LDL Xc. The decrease in LDL levels is dose-dependent and is exponential rather than linear.

The statins do not affect the activity of lipoprotein and hepatic lipases and have no significant effect on the synthesis and catabolism of free fatty acids, so their effect on TG levels is secondary and mediated through their main effects on reducing LDL-C levels. A moderate decrease in TG levels during treatment with statins seems to be due to the expression of remnant (apo E) receptors on the surface of hepatocytes involved in catabolism of LDL, which includes approximately 30% of TG.

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

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

Indications

Hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other nonmedicamental therapies (e.g., exercise, weight loss) are not sufficient.

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

Active ingredient

Composition

Shell composition: lactose monohydrate – 4.8 mg, hypromellose – 3.36 mg, titanium dioxide – 2.874 mg, triacetin – 0.96 mg, quinoline yellow – 0.006 mg.

Interaction

In concomitant use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was, on average, 7 times higher than that observed in healthy volunteers, while the plasma concentration of cyclosporine did not change.

The initiation of therapy with rosuvastatin or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (e.g., warfarin) may increase prothrombin time and INR, and discontinuation of rosuvastatin or reduction of the dose may decrease INR (INR monitoring is recommended in these cases).

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

Concomitant use of rosuvastatin and antacids containing aluminum and magnesium hydroxide leads to a decrease in plasma concentration of rosuvastatin by approximately 50%. This effect is weaker if antacids are used 2 h after taking rosuvastatin (clinical significance is unknown).

The concomitant use of rosuvastatin and erythromycin decreases AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30% (probably due to increased intestinal motility caused by taking erythromycin).

The concomitant use of rosuvastatin and oral contraceptives increases AUC of ethinylestradiol and AUC of nogestrel by 26% and 34%, respectively. This interaction cannot be excluded in concomitant use of rosuvastatin and hormone replacement therapy.

Hemfibrozil, other fibrates and hypolipidemic doses of nicotinic acid (≥1 g/day) increased the risk of myopathy when used concomitantly with other HMG-CoA reductase inhibitors possibly due to the fact that they can also cause myopathy when used as monotherapy.

The co-administration of rosuvastatin and itraconazole (CYP3A4 inhibitor) increases AUC of rosuvastatin by 28% (clinically insignificant).

Directions for use

The drug is taken orally. The tablet should be swallowed whole with water, without chewing or crushing. The drug can be taken at any time of the day regardless of meals.

Before starting treatment, patients should begin a diet of low cholesterol foods, which should be continued for the duration of treatment.

The dose of the drug should be adjusted individually depending on the goals of therapy and response to treatment, taking into account current accepted recommendations for target lipid concentrations.

If a 5-mg dose is necessary, it is recommended that rosuvastatin be used in another dosage form or dosage form, such as 5-mg tablets or 10-mg tablets with a rice (the 10-mg tablet should be divided into two parts by rice).

The recommended starting dose of the drug is 5 mg or 10 mg once daily both for patients who have not previously taken statins and for patients switched to this drug after therapy with other HMG-CoA reductase inhibitors. When choosing the initial dose, the cholesterol level in each individual patient should be taken into account and the possible risk of cardiovascular complications should be taken into account, as well as the potential risk of side effects. If necessary, the dose may be increased after 4 weeks.

. Because of possible development of side effects when using 40 mg dose, compared to lower doses of the drug, titration to a maximum dose of 40 mg during 4 weeks of therapy can be conducted only in patients with severe hypercholesterolemia and with high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia) in whom the desired therapy effect was not achieved with 20 mg dose, and who will be under medical supervision.

When prescribing the drug in a dose of 40 mg, close patient monitoring is recommended. Administration of 40 mg is not recommended in patients who have not previously seen a physician.

After 2-4 weeks of therapy and/or if the drug dose is increased, lipid metabolism parameters should be monitored; if necessary, the dose should be adjusted.

The dose of the drug should be adjusted if it is necessary to combine it with drugs that increase exposure to rosuvastatin. If an increase in exposure of 2 or more times is expected, the initial dose of the drug should be 5 mg once daily. The maximum daily dose should also be adjusted so that the expected exposure to rosuvastatin does not exceed that of a 40 mg dose taken without concomitant administration of drugs that interact with rosuvastatin (see section “Interaction with other medicinal products” in Table 1).

Patients of advanced age do not require dose adjustment.

In patients with mild to moderate renal failure, no dose adjustment is required. In patients with severe renal failure (CKD)

The drug is contraindicated in patients with active liver disease.

In patients of mongoloid race there may be increased systemic concentration of rosuvastatin. This fact should be taken into account when prescribing the drug in these groups of patients. When administering the drug in doses of 10 mg and 20 mg the recommended initial dose of the drug for Mongoloid patients is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in these patients.

When prescribing the drug in doses of 10 mg and 20 mg, the recommended starting dose for patients with predisposition to myopathy is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.

Special Instructions

Use with caution in the presence of risk factors for rhabdomyolysis (including renal failure, hypothyroidism, personal or family history of hereditary muscle disease and previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates), chronic alcoholism, in patients over 65 years of age, with a history of liver disease, sepsis, arterial hypotension, extensive surgery, trauma, severe metabolic endocrine or electrolyte disorders, uncontrolled epilepsy, in persons of Asian origin (Chinese, Japanese).

The therapy should be discontinued if the CPK level is significantly increased (more than 5 times the IGN level) or if muscle symptoms are severe and cause daily discomfort (even if the CPK level is 5 times less than the IGN level).

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

In most cases proteinuria decreases or disappears during therapy and does not indicate acute or progressive existing renal disease.

A higher incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrin acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when concomitantly prescribed with some HMG-CoA reductase inhibitors. Thus, concomitant administration of rosuvastatin and gemfibrozil is not recommended. The risk/benefit ratio of co-administration of rosuvastatin and fibrates or niacin should be carefully weighed.

Liver function tests are recommended before therapy and 3 months after the start of therapy. Rosuvastatin should be discontinued or the dose should be reduced if serum transaminase activity is 3 times greater than BHN.

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

Impact on driving and operating machinery

Patients should be aware that dizziness may occur during therapy when engaged in potentially hazardous activities.

Features

After oral administration the Cmax of rosuvastatin in blood plasma is reached after about 5 h. Bioavailability is approximately 20%.

Rosuvastatin is accumulated in the liver. Vd is approximately 134 liters. Binding to plasma proteins (predominantly to albumin) is approximately 90%.

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

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

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

As with other HMG-CoA-reducase inhibitors, hepatic uptake of rosuvastatin involves the membrane Xc transporter, which has an important role in hepatic elimination of rosuvastatin.

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

In patients with severe renal impairment (CK< 30 ml/min), plasma concentrations of rosuvastatin are 3 times higher and N-dismethyl concentrations are 9 times higher than in healthy volunteers. Plasma concentrations of rosuvastatin were approximately 50% higher in patients on hemodialysis than in healthy volunteers.

In patients with hepatic impairment with grade 8 and 9 on the Child-Pugh scale, there was an increase in T1/2 of at least 2-fold.

Contraindications

Side effects

CNS disorders: often – headache, dizziness, asthenic syndrome; possibly – anxiety, depression, insomnia, neuralgia, paresthesias.

In the digestive system:: frequently – constipation, nausea, abdominal pain; possible – reversible transient dose-dependent increase of liver transaminases activity, dyspepsia (including diarrhea, flatulence, vomiting), gastritis, gastroenteritis.

Respiratory system: often – pharyngitis; possibly – rhinitis, sinusitis, bronchial asthma, bronchitis, cough, dyspnea, pneumonia.

Cardiovascular system: possible – angina pectoris, increased BP, palpitations, vasodilation.

Muscular system: often – myalgia; possible – arthralgia, arthritis, muscle hypertonicity, back pain, pathological limb fracture (without injury); rarely – myopathy, rhabdomyolysis (concomitantly with impaired renal function, with the drug at a dose of 40 mg).

Urinary system disorders: tubular proteinuria (in less than 1% of cases for 10 and 20 mg doses, 3% of cases for 40 mg dose); possibly peripheral edema (hands, feet, ankles, shins), lower abdominal pain, urinary tract infections.

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

Laboratory parameters: transient dose-dependent increase of CPK activity (in case of an increase of CPK activity more than 5-fold compared to CHF the therapy should be temporarily suspended).

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

Similarities