Description
Latin name
MERTENIL
Release form
Coated tablets.
Packaging
In a blister pack of 10 tablets. There are 3 blisters in the package.
Pharmacological action of
Mertenyl is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, which is the precursor of cholesterol. rosuvasta ina is the liver, where the synthesis of cholesterol (LDL) and catabolism of low density lipoprotein (LDL).
Rosuvastatin increases the number of “liver” LDL receptors on the cell surface, increasing the catabolism of LDL and seizure.
It also inhibits the synthesis of very low density lipoprotein cholesterol (VLDL) in liver cells, thereby reducing the total content of LDL and VLDL.
Rosuvastatin lowers high cholesterol – LDL (cholesterol-LDL), total cholesterol and triglycerides (TG), increases cholesterol high density lipoprotein (cholesterol-HDL), and also reduces the content of apolipoprotein B (ApoV), cholesterol-non-HDL cholesterol minus HDL cholesterol, cholesterol-VLDL, TG-VLDL and increases the level of apolipoprotein A-1 (ApoA-1). Rosuvastatin reduces the ratio of cholesterol-LDL / cholesterol-HDL, total cholesterol-HDL, HDL-HDL / C and ApoB / ApoA-1.
Therapeutic effect can be achieved a within one week after the start of treatment, after 2 weeks, 90% of the maximum possible effect is achieved. Usually, the maximum possible therapeutic effect is achieved after 4 weeks and is maintained with further administration of the drug.
– Clinical efficacy Rosuvastatin is effective in the treatment of adult patients with hypercholesterolemia with or without symptoms of hypertriglyceridemia, regardless of race, gender or age, as well as in the treatment of a special category of patients with diabetes mellitus or a hereditary form of familial hypercholesterolemia.
Rosuvastatin is effective for the treatment of patients with type IIa and IIb hypercholesterolemia according to Frederickson (average baseline LDL-C level okopo 4.8 mmol / L). In 80% of patients treated with 10 mg of rosuvastatin, the target values of the level of LDL-C established by the European Society for the Study of Atherosclerosis (less than 3 mmol / l) were achieved. In patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses of 20 to 80 mg according to the forced dose titration scheme, all doses taken had a significant effect on changing the parameters characterizing the lipid content and on achieving the goal of therapy.
As a result of titration of doses up to 40 mg per day (12 weeks of therapy), the content of LDL-C decreased by 53%. In 33% of patients, LDL-C values (below 3 mmol / L) were achieved that meet the target standards of the guidelines of the European Society for the Study of Atherosclerosis. In patients with homozygous familial hypercholesterolemia who took rosuvastatin in doses of 20 and 40 mg, the average decrease in LDL-C was 22%.
The additive effect is observed in combination with fenofibrate in relation to the content of TG and with nicotinic acid (more than 1 g per day) in relation to the content of HDL-C. Studies on the effect of rosuvastatin on reducing the number of complications caused by lipid disorders, such as coronary artery disease, have not yet been completed.
In patients with a low risk of coronary heart disease (defined as a Framingham risk of less than 10% for a period of more than 10 years), with an average LDL-C content of 4.0 mmol / l (154.5 mg / dl) rosuvastatin at a dose of 40 mg / day significantly slowed down the increase in the maximum value characterizing the thickening of the wall of the carotid artery in 12 segments, compared with placebo at a rate of -0.0145 mm / year (95% confidence interval: from -0.0196 to – 0 , 0093, with p
Indications
– Hypercholesterolemia and combined (mixed) dyslipidemic conditions to reduce elevated concentrations of total cholesterol, low-density lipoprotein cholesterol, apo-lipoprotein B and serum triglycerides as an adjunct to diet therapy, when dietary and other non-medication exercises, weight loss) are insufficient.
– Family homozygous hypercholesterolemia as an adjunct to diet therapy and other lipid-lowering therapy (eg, LDL apheresis) or in cases where such therapy is not effective enough.
Contraindications
– Hypersensitivity to rosuvastatin or any of the components of the drug.
– Liver diseases in the active phase, including a persistent increase in the activity of liver transaminases, as well as any increase in the activity of transaminases in blood serum by more than 3 times compared with the upper limit of normal.
– Severe renal impairment (QC less than 30 ml / minute).
– Myopathy.
– Concomitant use of cyclosporine.
– In patients predisposed to the development of myotoxic complications.
– Pregnancy.
– Lactation.
– In women of childbearing age who do not use reliable contraceptives.
– Age under 18 years of age (efficacy and safety not established).
– Patients with liver failure with a score of greater than 9 on the Childe-Pugh scale.
– Lactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Precautions:
– Risk of developing myopathy / rhabdomyolysis, including: – Renal failure.
– Hypothyroidism.
– A personal or family history of hereditary muscle disease and a previous history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates.
Use during pregnancy and pregnancy Lactation has been used during pregnancy. Women of childbearing age should use reliable and adequate contraceptives.
Since cholesterol and cholesterol biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefits of its use in pregnancy. In case of pregnancy, the drug should be stopped immediately.
– Lactation:
There are no data on the excretion of the drug with breast milk. If necessary, the appointment of the drug during lactation, breastfeeding must be stopped.
Composition of
In 1 film-coated tablet contains:
Active ingredient:
– Calcium rosuvastatin 10.4 mg., which corresponds to the content of rosuvastatin 10 mg.
Excipients:
Microcrystalline cellulose 12,
lactose monohydrate,
magnesium hydroxide,
crospovidone (type A),
magnesium stearate.
Composition of the film coat:
Opadray II white (talc, macrogol-3350, titanium dioxide (E171), polyvinyl alcohol).
Dosage and administration of
Before starting treatment, the patient should follow a standard diet with low cholesterol products, which should be continued throughout the treatment period. Doses of the drug should be selected individually in accordance with the purpose of the treatment and the patient’s therapeutic response to the therapy, taking into account current generally accepted recommendations for target lipid levels.
Inside, at any time of the day, regardless of food intake, do not chew or grind, swallow whole, washed down with water.
The recommended initial dose of the drug is 5 mg or 10 mg 1 time per day for patients who have not previously taken statins, and for patients transferred to receive this drug after treatment with other HMG-CoA reductase inhibitors.
Choosing an initial dose of a drug, one should take into account the level of cholesterol in each individual patient, as well as the possible risk of developing cardiovascular complications and the potential risk of side effects.
If necessary, after 4 weeks you can make a dose adjustment.
Due to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug, the final titration to a maximum dose of 40 mg should be carried out only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia), in which when taking a dose of 20 mg, the target cholesterol level was not achieved, and which will be under medical supervision. When prescribing a dose of 40 mg, close medical supervision is recommended. A dosage of 40 mg is not recommended for patients who have not previously consulted a doctor!
– In elderly patients For patients older than 70 years, the recommended initial dose of the drug is 5 mg. Dose adjustment due to age is not required.
– For renal failure In patients with mild or moderate renal failure, dose adjustment is not required. The recommended initial dose of the drug is 5 mg for patients with moderate renal failure (CC less than 60 ml / minute). The appointment of Mertenil in any dose is contraindicated in patients with severe renal failure. For patients with moderate renal failure, the appointment of a drug in a dose of 40 mg is contraindicated.
– In Hepatic Failure An increase in systemic concentrations of rosuvastatin in patients with a Child-Pugh score of 7 or lower was not detected. However, an increase in systemic drug concentration was observed in patients with Child-Pugh scores of 8 and 9. In such patients, liver function should be monitored during therapy. There are no data on the administration of the drug by patients with a Child-Pugh score higher than 9. Patients with liver disease 8 active phase Mertenil is contraindicated.
– In ethnic groups In patients of the Asian race, an increase in the systemic concentration of rosuvastatin is possible. When prescribing doses of 10 and 20 mg, the recommended initial dose of the drug for patients of Asian origin is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.
– With a predisposition to myopathy When prescribing doses of 10 and 20 mg, the recommended initial dose of the drug 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.
For ease of use, it is also possible to use the drug in other dosages:
Side effects of
As with other HMG-CoA reductase inhibitors, the incidence of side effects is dose-dependent.
The incidence of rhabdomyolysis, severe side effects from the kidneys and liver increases in patients taking rosuvastatin at a dose of 40 mg.
From the urinary system: when taking rosuvastatin, proteinuria was observed, mainly of tubular origin. Changes in protein in the urine (from the absence or presence of trace amounts to the level of ++ and above) were found in less than 1% of patients taking rosuvastatin in doses of 10 mg and 20 mg, and in about 3% of patients taking the drug at a dose of 40 mg.
The minimum change in the amount of protein in the urine, expressed as a change from zero level or the presence of traces to level +, was observed when taking the drug at a dose of 20 mg. In most cases, proteinuria decreased and passed independently during treatment. An analysis of clinical trial data did not reveal a causal relationship between proteinuria and acute or progressive kidney disease. In a number of patients treated with rosuvastatin, hematuria was observed, but clinical trial data showed that the incidence of such cases is very low.
From the musculoskeletal system: the effect on skeletal muscle causing myalgia, myopathy (including myositis) and, in rare cases, rhabdomyolysis with or without the development of acute renal failure, observed in patients taking any dose of rosuvastatin, in particular a dose of more than 20 mg. An increase in the content of CPK depending on the dose taken was found in patients taking rosuvastatin, but in most cases these manifestations were minor, asymptomatic and temporary. If the content of CPK is 5 times higher than VGN, then treatment should be discontinued.
From the liver: as with other HMG-CoA reductase inhibitors, an increase in hepatic transaminase activity depending on the dose was detected in a small number of patients taking rosuvastatin. Moreover, in most cases, this increase was moderately pronounced, asymptomatic and transient.
On the part of laboratory indicators: an increase in the concentration of glucose, bilirubin, the activity of GGT, alkaline phosphatase, impaired thyroid function.
Post-marketing use of
From the digestive system: very rarely – jaundice, hepatitis rarely – increased activity of hepatic transaminases, unspecified frequency – diarrhea.
From the musculoskeletal system: very rarely – arthralgia.
From the nervous system: very rarely – polyneuropathy, memory loss.
From the respiratory system: unspecified frequency – cough, shortness of breath.
From the urinary system: very rarely – hematuria.
Dermatological reactions: unspecified frequency – Stevens-Johnson syndrome.
Other: unspecified frequency – peripheral edema.
The following side effects have been reported with some statins: depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction.
Isolated cases of interstitial lung disease have been reported, especially with prolonged use of drugs.
Drug Interaction
Cyclosporine:
When co-administered with rosuvastatin and cyclosporine, the AUC of rosuvastatin increased 7-fold compared with healthy subjects. Co-administration results in an 11-fold increase in the concentration of rosuvastatin in blood plasma. No changes in the concentration of cyclosporine in the blood plasma were observed with concomitant administration.
Vitamin K antagonists:
As with other HMG-CoA reductase inhibitors, initiation of rosuvastatin therapy or increasing the drug dose in patients, receiving simultaneously vitamin K antagonists (eg, warfarin or other coumarin anticoagulants) may lead to an increase in International Normalized Ratio (MHO). Withdrawing or reducing the dose of rosuvastatin may cause a decrease in MHO. In such cases, MHO monitoring should be carried out.
Ezetimibe:
No changes in AUC or both are observed with rosuvastatin and ezetimibe. However, the pharmacodynamic interaction of rosuvastatin and ezetimibe, which may cause undesirable effects, cannot be excluded.
Gemfibrozil and other lipid-lowering agents:
Concomitant administration of rosuvastatin and gemfibrozil results in a 2-fold increase in the max and AUC of rosuvastatin. Based on specific interaction studies, no appropriate pharmacokinetic interaction with fenofibrates is expected, but pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and nicotinic acid in lipid-lowering doses (1 g or more per day) when co-administered with HMG-CoA reductase inhibitors increased the risk of myopathy, possibly due to the fact that they may cause myopathy and cause myopathy. in monotherapy. When co-administered with gemfibrozil and other lipid-lowering agents, the starting dose of Mertenil should not exceed 5 mg.
Protease Inhibitors:
Although the exact mechanism of interaction is unknown, concomitant administration of rosuvastatin with protease inhibitors may lead to a prolongation of the half-life of rosuvastatin. In a pharmacokinetic study, 20 mg of rosuvastatin and a combination drug containing two protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir) were found by healthy volunteers to increase 2-fold AUC) and 5-fold C max of rosuvastatin, respectively. Therefore, it is not recommended to prescribe rosuvastatin and protease inhibitors in the treatment of HIV patients at the same time.
Antacids:
Concomitant administration of rosuvastatin and antacids in suspensions containing aluminum or magnesium hydroxide can reduce the plasma concentration of rosuvastatin by about 50%. This action is less pronounced if antacids are administered 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.
Erythromycin:
Concomitant administration of rosuvastatin and erythromycin may result in a 20% decrease in the AUC (0-1) of rosuvastatin and a 30% reduction in rosuvastatin C max. This relationship can be caused by increased intestinal motility caused by the intake of erythromycin.
Oral contraceptives / hormone replacement therapy:
Concomitant administration of rosuvastatin and oral contraceptives may increase ethinyl estradiol and norgestrel AUC by 26% and 34%, respectively.
This increase in plasma concentrations should be considered when choosing a dose of oral contraceptives. There are no pharmacokinetic data on the concomitant use of rosuvastatin and hormone replacement therapy, so no similar effect can be ruled out when using this combination. However, such a combination of drugs was widely used by women in clinical trials and was well tolerated.
Other medicines:
No clinically relevant interaction is expected when co-administered with rosuvastatin and digoxin.
Cytochrome P450 isoenzymes:
In vifro and in vivo studies showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak enough substrate for these enzymes. No clinically relevant interaction was detected between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4 isoenzymes) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes).
Co-administration of itraconazole (a CYP3A4 isoenzyme inhibitor) and rosuvastatin increases rosuvastatin AUC by 28% (not clinically relevant). Therefore, no drug interaction related to cytochrome P450 metabolism is expected.
Overdose
– Symptoms: increased side effects.
– Treatment: There is no specific treatment for overdose.
In case of overdose, it is recommended to carry out symptomatic treatment and supportive measures. Liver function and the degree of CPF activity should be monitored.
Hemodialysis in this case is probably ineffective.
Storage conditions
– Store in a dry, dark place at a temperature not exceeding 30 ° C.
– Keep out of the reach of children.
– Do not use after the expiration date.
Expiration
2 years.
Deystvuyuschee substances
rosuvastatin
pharmacy outlets p177 pharmacy package
Prescription
dosage form
dosage form
tablets
Gedeon Richter Vengriya
