Rozistark pills 40mg, 56pcs

Composition

of 1 tab. rosuvastatin calcium is 41.6 mg, which corresponds to the content of rosuvastatin 40 mg. Excipients: lactose monohydrate-229.645 mg, microcrystalline cellulose-109.355 mg, crospovidone-16 mg, magnesium stearate-3.4 mg.

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

Pharmacological action

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

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

Statins do not affect the activity of lipoprotein and hepatic lipases, do not significantly affect the synthesis and catabolism of free fatty acids, so their effect on TG levels is secondary and mediated through their main effects on lowering LDL-C levels. A moderate decrease in TG levels during statin treatment appears to be associated with the expression of remnant (apo E) receptors on the surface of hepatocytes involved in the catabolism of STDs, which comprise approximately 30% of 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 manifests itself 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 remains constant after that.

Indications

Hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a dietary supplement when diet and other non-drug treatments (e. g., exercise, weight loss) are insufficient.

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

Recommendations for use

They are taken orally. 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), if the 20 mg dose is not effective enough and under the supervision of a doctor.

Contraindications

Liver diseases in the active phase (including a persistent increase in the activity of hepatic transaminases or any increase in transaminase activity by more than 3 times compared to the ULN), severe renal dysfunction (creatinine clearance

Side effects

From 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-reversible transient dose-dependent increase in the activity of hepatic transaminases, dyspepsia (including diarrhea, flatulence, vomiting), gastritis, gastroenteritis.

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

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

Musculoskeletal disorders:  often – myalgia; possible-arthralgia, arthritis, muscle hypertonus, back pain, pathological fracture 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 (hands, feet, ankles, shins), pain in the lower abdomen, urinary tract infections.

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

From the side of laboratory parameters:  transient dose-dependent increase in CPK activity (if CPK activity increases more than 5 times compared to ULN, therapy should be temporarily suspended).

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

Interaction

When rosuvastatin and cyclosporine were co-administered, 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.

Starting rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in prothrombin time and INR, and discontinuing rosuvastatin or reducing the dose 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.

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).

Concomitant use of rosuvastatin and erythromycin leads to a decrease in rosuvastatin AUC by 20% and rosuvastatin cmax by 30% (probably as a result of increased intestinal motility caused by erythromycin).

Concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and 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 co-administered with other HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when used as monotherapy.

Co-use of rosuvastatin and itraconazole (a CYP3A4 inhibitor) increases the AUC of rosuvastatin by 28% (clinically insignificant).

Functional features

After oral use, cmax of rosuvastatin in blood plasma is reached in approximately 5 hours. Bioavailability is approximately 20%.

Rosuvastatin accumulates in the liver. V_d is approximately 134 l. The binding to plasma proteins (mainly albumin) is approximately 90%.

Biotransformed to a small extent (about 10%), being a non-core substrate for cytochrome P 450 isoenzymes. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. The isoenzymes CYP2C19, CYP3A4, and CYP2D6 are less involved in metabolism.

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

About 90% of the rosuvastatin dose is excreted unchanged in the faeces. The remainder is excreted in the urine. Plasma T_1/2 – approximately 19 h. T_1/2 does not change with increasing dose. The average plasma clearance is approximately 50 l / h (coefficient of variation 21.7%).

As with other HMG-CoA reductase inhibitors, the hepatic uptake of rosuvastatin involves a membrane Cholesterol transporter that plays an important role in the hepatic elimination of rosuvastatin.

Systemic exposure to rosuvastatin increases in proportion to the dose.

In patients with severe renal insufficiency (CC The plasma concentration of rosuvastatin in hemodialysis patients was approximately 50% higher than in healthy volunteers.

In patients with hepatic insufficiency, the degree of which was 8 and 9 on the Child-Pugh scale, an increase in T_{1/2 was noted} at least 2 times.

Special instructions

Use with caution in the presence of risk factors for rhabdomyolysis (including renal failure, hypothyroidism, a 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 over the age of 65, with a history of liver disease, sepsis, arterial hypotension, during extensive surgical interventions, injuries, severe metabolic disorders. endocrine or electrolyte disorders, uncontrolled epilepsy, in people of Asian descent (Chinese, Japanese).

Therapy should be discontinued if the CK level is significantly increased (more than 5 times higher than ULN) or if muscle symptoms are severe and cause daily discomfort (even if the CK level is 5 times lower than ULN).

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

In most cases, proteinuria decreases or disappears during therapy and does not indicate the occurrence of acute or progressive existing kidney disease.

An increased incidence of myositis and myopathy has been reported in patients treated with other HMG-CoA reductase inhibitors in combination with fibrinic acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid, azole antifungal drugs, protease inhibitors, and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Therefore, concomitant use of rosuvastatin and gemfibrozil is not recommended. The risk-benefit ratio of rosuvastatin and fibrates or niacin should be carefully weighed.

It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. The use of rosuvastatin should be discontinued or the dose should be 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, treatment of the underlying diseases should be carried out before starting treatment with rosuvastatin.

Influence on the ability to drive motor vehicles and manage mechanisms

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

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets