Description
Pharmacological action
Rosart – a lipid-lowering drug from the group of statins. Selective competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) – reductase – an enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol. It increases the number of low density lipoprotein receptors (LDL) on the surface of hepatocytes, which leads to increased uptake and catabolism of LDL, inhibition of very low density lipoprotein synthesis (VLDL), reducing the total number of LDL and VLDL.
Reduces elevated concentrations of LDL cholesterol, low-density lipoprotein cholesterol (non-HDL), VLDL cholesterol, total cholesterol, triglycerides (TG), VL-VLDL, apolipoprotein B (ApoV), lowers the ratio of total cholesterol-LP-Lp-cholesterol-Lp / Lp cholesterol / HDL cholesterol, non-HDL cholesterol / HDL cholesterol, ApoV / apolipoprotein AI (ApoA-I), increases the concentration of HDL cholesterol and ApoA-I.
Hypolipidemic effect is directly proportional to the size of the prescribed dose. The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks reaches 90% of the maximum, by 4 weeks reaches a maximum and after that remains constant. Effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender or age), including in patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with type IIa and IIb hypercholesterolemia (Fredrickson classification) with an average baseline LDL cholesterol of about 4.8 mmol / L while taking the drug at a dose of 10 mg, the LDL cholesterol concentration reaches values ​​of less than 3 mmol / L. In patients with homozygous familial hypercholesterolemia taking the drug at a dose of 20 mg and 40 mg, the average decrease in LDL cholesterol concentration is 22%.
The additive effect is observed in combination with fenofibrate (in relation to a decrease in the concentration of TG) and with nicotinic acid in lipid lowering doses> 1 g / day (in relation to an increase in the concentration of HDL cholesterol).
Pharmacokinetics
Absorption
The maximum concentration (Cmax) of rosuvastatin in plasma is reached approximately 5 hours after taking the drug. Absolute bioavailability is approximately 20%. The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily use.
Distribution
Crosses the placental barrier. Rosuvastatin is predominantly absorbed by the liver, which is the main site of cholesterol synthesis and metabolism of LDL-C. Distribution volume – 134 l. Binding to plasma proteins (mainly with albumin) is approximately 90%.
Metabolism
Biotransformed in the liver to a small extent (about 10%), being a non-core substrate for isoenzymes of the cytochrome P450 system. As in the case of other HMG-CoA reductase inhibitors, a specific membrane carrier is involved in the process of hepatic uptake of the drug – a polypeptide transporting the organic anion (OATP) 1B1, which plays an important role in its hepatic elimination. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. Isoenzymes CYP2C19, CYP3A4, and CYP2D6 are less involved in metabolism. The main metabolites of rosuvastatin are N-desmethyl and lactone metabolites. N-desmethyl is approximately 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is metabolites.
Excretion
About 90% of the dose of rosuvastatin is excreted unchanged through the intestines, the remainder by the kidneys. The half-life (T1 / 2) is approximately 19 hours, does not change with an increase in the dose of the drug. The average plasma clearance is approximately 50 l / h (coefficient of variation 21.7%).
In patients with mild to moderate renal failure, the plasma concentration of rosuvastatin or N-desmethyl does not change significantly. In patients with severe renal failure (creatinine clearance (CC) less than 30 ml / min), the concentration of rosuvastatin in plasma is 3 times higher, and N-desmethyl is 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in patients on hemodialysis is approximately 50% higher than in healthy volunteers.
Patients with various stages of liver failure with a score of 7 or lower on the Child-Pugh scale did not show an increase in T1 / 2 of rosuvastatin in patients with a score of 8 and 9 on the Child-Pugh scale, a 2-fold elongation of T1 / 2 was noted. There is no experience with the use of the drug in patients with more severe impaired liver function. Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin. Pharmacokinetic parameters depend on race: the area under the concentration-time curve (AUC) in Japanese and Chinese is 2 times higher than that of residents of Europe and North America. In representatives of the Mongoloid race and Indians, the average value of AUC and Cmax increases by 1.3 times.
Indications
Primary hypercholesterolemia (type IIa according to Fredrickson), including heterozygous hereditary hypercholesterolemia) or mixed (combined) hyperlipidemia (type IIb according to Fredrickson), as an addition to diet and other non-drug measures (physical activity and weight loss)
Homozygous form of hereditary hypercholesterolemia with insufficient effectiveness of diet therapy and other types of treatment aimed at lowering lipids (for example, LDL apheresis) or, if such treatments are not fit the patient.
Hypertriglyceridemia (type IV Fredrickson supplementation) as a diet supplement.
To slow the progression of atherosclerosis as a supplement to the diet in patients who are shown therapy to lower total cholesterol and LDL cholesterol.
Prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), but with an increased risk of its development (age over 50 for men and over 60 for women, increased concentration of C-reactive protein ( 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low concentration of HDL cholesterol, smoking, family history of early onset of coronary heart disease).
Contraindications of
liver disease in the active phase, including a persistent increase in serum activity of hepatic transaminases (more than 3 times compared with VGN) of unknown genesis
severe renal dysfunction (CC less than 30 ml / min)
myopathy
simultaneous administration women of reproductive age who do not use adequate methods of contraception
pregnancy and lactation
age up to 18 years (efficacy and safety have not been established)
lactose intolerance, lactase deficiency s glucose-galactose malabsorption (the drug contains lactose monohydrate)
hypersensitivity to rosuvastatin or other components of the
drug Caution: the presence of risk factors for myopathy and / or rhabdomyolysis – renal failure (CC more than 30 ml / min), hypothyroidism, personal or family history hereditary muscle diseases and a previous history of myotoxicity with other HMG-CoA reductase inhibitors or fibrates, excessive alcohol consumption, age over 70 years old, with cat ryh marked increase in plasma concentrations of rosuvastatin race (Mongoloid race), the simultaneous application of a fibrate, a history of liver disease, septicemia, hypotension, extensive surgery, trauma, severe metabolic, endocrine or electrolyte disturbances or uncontrolled epilepsy.
Use during pregnancy and lactation
Rosart is contraindicated in pregnancy and lactation.
The use of Rosart in women of reproductive age is possible only if reliable methods of contraception are used and if the patient is informed about the possible risk of treatment for the fetus.
Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefits of using the drug during pregnancy. In the case of diagnosing pregnancy during therapy with Rosart, the drug should be stopped immediately, and patients should be warned of the potential risk to the fetus.
No data are available on the excretion of rosuvastatin in breast milk, therefore, if it is necessary to use the drug during lactation, given the possibility of adverse events in infants, the issue of stopping breastfeeding should be addressed.
Ingredients
Active ingredient: rosuvastatin 5 mg
Excipients: microcrystalline cellulose, type 102, crospovidone, type A, calcium hydrogen phosphate dihydrate, lactose monohydrate, magnesium
stearate Laminate white, white platinum, 33, white hydrofoam, 33 , macrogol-3350, triacetin).
Side effects
From the central nervous system: often – headache, dizziness, asthenic syndrome infrequently – depression, anxiety, insomnia, paresthesia very rarely – peripheral neuropathy, memory loss.
From the digestive system: often – nausea, constipation, abdominal pain infrequently – vomiting, diarrhea, flatulence rarely – pancreatitis is very rare – hepatitis, jaundice.
From the respiratory system: often – pharyngitis infrequently – rhinitis, sinusitis, bronchial asthma, bronchitis, cough, dyspnea, pneumonia.
From the cardiovascular system: infrequently – angina pectoris, increased blood pressure, palpitations, vasodilation.
From the endocrine system: often – diabetes 1. (The overall frequency of 2.8% in the rosuvastatin group and 2.3% in the placebo group, mainly in patients with fasting glucose of 5.6 – 6.9 mmol / l, was reported in the JUPITER study.
From the musculoskeletal system: often – myalgia rarely – arthralgia myopathy (including myositis), rhabdomyolysis, back pain, muscle hypertonicity, pathological fracture of the extremities is very rare – immune-mediated necrotizing myopathy.
Allergic reactions: infrequently – skin itching, rash, urticaria, rarely – angioedema.
Skin and subcutaneous tissue: frequency unknown – Stevens-Johnson syndrome.
From the urinary system: often – proteinuria (mainly in patients receiving a dose of 40 mg), which decreases during therapy and is not associated with the occurrence of kidney disease, urinary tract infections are rare – peripheral edema, pain in the lower abdomen is very rare – hematuria.
Laboratory indicators: infrequently – a transient dose-dependent increase in serum creatine phosphokinase (CPK) activity, with an increase of more than 5 times compared with VGN, therapy should be temporarily suspended rarely – a transient increase in the activity of aspartate aminotransferase and alanine aminotransferase.
Other: often – back pain, rhinopharyngitis rarely – decreased potency.
As with other HMG-CoA reductase inhibitors, the incidence is dose-dependent, side effects are usually mild and go away on their own.
Drug interaction
The simultaneous use of rosuvastatin and cyclosporine does not affect the plasma concentration of cyclosporine, however, the effect of rosuvastatin is enhanced (its excretion is slowed, AUC increases by 7 times, Cmax – by 11 times).
Erythromycin enhances intestinal motility, which leads to a decrease in the effect of rosuvastatin (AUC decreases by 20% and Cmax by 30%).
In patients receiving vitamin K antagonists (e.g. warfarin) monitoring of MHO is recommended, since the initiation of therapy with rosuvastatin or an increase in the dose of the drug can lead to an increase in MHO, and the withdrawal of rosuvastatin or a decrease in its dose can lead to its decrease.
Gemfibrozil enhances the effect of rosuvastatin (increases Cmax and AUC by 2 times). 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.
The simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively, which should be considered when selecting a dose of oral contraceptives. There are no pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy, therefore, a similar effect cannot be excluded when using this combination.
The results of studies showed that rosuvastatin is neither an inhibitor nor an inducer of the action of cytochrome P450 isoenzymes. Rosuvastatin is a non-core substrate for these isoenzymes. There was no clinically significant interaction with drugs such as fluconazole, ketoconazole and itraconazole associated with the metabolism of the cytochrome P450 system.
No clinically significant interaction of rosuvastatin with digoxin or fenofibrate has been observed. Gemfibrozil other fibrates and hypolipidemic doses of nicotinic acid (at least 1 g / day) increased the risk of myopathy while using other HMG-CoA reductase inhibitors. Perhaps due to the fact that they can cause myopathy when used as monotherapy.
The combined use of rosuvastatin and ezetimibe did not lead to changes in the AUC or Cmax of both drugs.
The use of protease inhibitors with rosuvastatin can lead to a marked increase in the effect of rosuvastatin. Thus, co-administration of rosuvastatin with protease inhibitors to HIV-infected patients is not recommended.
Overdose of
With the simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.
Treatment: there is no specific treatment, symptomatic therapy is carried out under the control of liver function and CPK activity. Hemodialysis is ineffective.
active substance
Rosuvastatin
drugstore drugstore
drugstore ovyya otpuska IZ
pharmacy prescription
lekarstvennaja form
tablets
Actavis Ltd, Iceland
