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: Â 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
The drug is taken orally. The tablet should be swallowed whole, washed down with water, without chewing or grinding. The drug can be taken at any time of the day, regardless of food intake.
Before starting treatment, the patient should begin to follow a diet with low cholesterol products, which should be continued throughout the entire treatment period.
The dose of the drug should be selected individually, depending on the goals of therapy and response to treatment, taking into account current generally accepted recommendations for target lipid concentrations.
If it is necessary to use the drug at a dose of 5 mg, it is recommended to use rosuvastatin in a different dosage form or dosage, for example,5 mg tablets or 10 mg tablets with a risk (a tablet at a dose of 10 mg should be divided into two parts according to risk).
The recommended starting dose of the drug is 5 mg or 10 mg 1 time/day for both patients who have not previously taken statins, and for patients transferred to the use of 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 should be assessed. If necessary, the dose can be increased after 4 weeks.
Due to the possible development of side effects when using the drug at a dose of 40 mg, compared with lower doses of the drug, titration to a maximum dose of 40 mg for 4 weeks of therapy can only be carried out in patients with severe hypercholesterolemia and at high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia), who did not achieve the desired effect of therapy when using the drug at a dose of 20 mg, and who will be under medical supervision.
When prescribing the drug at a dose of 40 mg, careful monitoring of the patient is recommended. It is not recommended to prescribe the drug at a dose of 40 mg to patients who have not previously consulted a doctor.
After 2-4 weeks of therapy and/or when increasing the dose of the drug, it is necessary to monitor the parameters of lipid metabolism, if necessary, the dose should be adjusted.
The dose of the drug should be adjusted if it is necessary to use it together with drugs that increase the exposure of rosuvastatin. If exposure is expected to increase by a factor of 2 or more, the initial dose of the drug should be 5 mg 1 time / day. It is also necessary to adjust the maximum daily dose of the drug so that the expected exposure of rosuvastatin does not exceed that for a dose of 40 mg taken without simultaneous use of drugs that interact with rosuvastatin (see the section “Interaction with other drugs” Table 1).
Elderly patients do not require dose adjustment.
No dose adjustment is required in patients with mild or moderate renal insufficiency. In patients with severe renal insufficiency (CC
The drug is contraindicated in patients with liver diseases in the active phase.
In patients of the Mongolian race, an increase in the systemic concentration of rosuvastatin is possible. This fact should be taken into account when prescribing the drug to these groups of patients. When prescribing the drug in doses of 10 mg and 20 mg, the recommended initial dose of the drug for patients of the Mongolian race is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.
When prescribing the drug in doses of 10 mg and 20 mg, the recommended initial dose for patients with a predisposition to myopathy is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.
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: Â 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: Â 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: Â 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: Â 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: Â 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. Vd 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 T1/2 – approximately 19 h. T1/2 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 T1/2 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
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