MERTENIL PILLS 20MG

Packaging

In the blister of 10 tablets. In packing 3 blisters.

Mechanism of action

Mertenil is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutarycoenzyme A to mevalonate, which is a precursor of cholesterol. The main target of Rosuvastatin action is the liver, where cholesterol (cholesterol) synthesis and low density lipoprotein catabolism (LDL) are performed.

Rosuvastatin increases the number of “liver” LDL receptors on the cell surface, increasing the uptake and catabolism of LDL.

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 reduces high cholesterol - LDL (cholesterol-LDL), total cholesterol and triglycerides (TG), increases the cholesterol of high-density lipoprotein (cholesterol-HDL cholesterol), and also reduces the content of apolipoprotein B (ApoB), cholesterol-HDLP (total cholesterol) less the cholesterol HDL, cholesterol-VLDL, TG-VLDL and increases the level of apolipoprotein A-1 (ApoA-1). Rozuvastatin reduces the ratio of LDL-LDL / LDL-HDL, total HSDS-HDL, HSL-LDLP / LDL ApoV / ApoA-1.

The therapeutic effect can be achieved and 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 the further intake of the drug.

- Clinical efficacy Rosuvastatin is effective in the treatment of adult patients with hypercholesterolemia with or without symptoms of hypertriglyceridemia, regardless of their race, gender, or age, as well as in the treatment of a special category of patients with diabetes or a hereditary form of familial hypercholesterolemia. Rosuvastatin is effective for the treatment of patients with hypercholesterolemia type IIa and IIb according to Frederickson (the mean baseline level of LDL-C LDL is 4.8 mmol / l). In 80% of patients who received 10 mg of rosuvastatin, the target values ​​of cholesterol-LDL levels established by the European Society for 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 the doses taken had a significant effect on the change in parameters characterizing 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), LDL-C content decreased by 53%. In 33% of patients, LDL-C LDL values ​​(below 3 mmol / l) were achieved, corresponding to the target standards of the guidelines of the European Society for Atherosclerosis Research. In patients with homozygous familial hypercholesterolemia who took rosuvastatin at doses of 20 and 40 mg, the average decrease in LDL-C content was 22%. An additive effect is observed in combination with fenofibrate in relation to the TG content 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 low risk of coronary heart disease (defined as framingham risk less than 10% over a period of more than 10 years), with an average LDL-C content of 4.0 mmol / L (154.5 mg / dL) rosuvastatin in a dose of 40 mg / day significantly slowed down the increase in the maximum value characterizing the thickening of the carotid artery wall 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 <0.0001).

Indications and usage

- Hypercholesterolemia and combined (mixed) dyslipidemic conditions to reduce elevated concentrations of total cholesterol, low-density lipoprotein cholesterol, apo-lipoprotein B, and serum triglycerides as a supplement to diet therapy when dieting and other non-drug methods (eg, exercise, weight loss body) are insufficient.
- Familial homozygous hypercholesterolemia as an adjunct to diet therapy and other methods of lipid-lowering therapy (for example, LDL-apheresis) or in cases when 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 serum transaminase activity by more than 3 times compared with the upper limit of normal.
- Severe renal dysfunction (CC less than 30 ml / minute).
- Myopathy.
- Simultaneous reception of cyclosporine.
- In patients predisposed to the development of myotoxic complications.
- Pregnancy.
- Lactation period.
- In women of childbearing age who do not use reliable contraceptives.
- Age up to 18 years (efficacy and safety have not been established).
- Patients with liver failure with a score above 9 on the Childe Pugh scale.
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

With caution:

- The risk of myopathy / rhabdomyolysis, including:
- Renal failure.
- Hypothyroidism.
- Personal or family history of hereditary muscular diseases and a previous history of muscular toxicity using other HMG-CoA reductase inhibitors or fibrates.

Pregnancy and Breastfeeding

- Pregnancy Mertenil is contraindicated for use during pregnancy and lactation. Women of childbearing age should use reliable and adequate contraception. Since cholesterol and cholesterol biosynthesis products are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of its use during pregnancy. In the event of pregnancy, the drug should be immediately discontinued.

- Lactation Data on the release of the drug in breast milk are not available. If necessary, the appointment of the drug during lactation breastfeeding should be stopped.

Dosage and administration

Before starting treatment, the patient should follow a standard diet with foods low in cholesterol, which should be continued during the entire period of treatment. Doses of the drug should be selected individually in accordance with the purpose of the treatment and the therapeutic response of the patient to the therapy, taking into account modern generally accepted recommendations on target lipid levels.

Inside, at any time of the day, regardless of the meal, do not chew or chop, swallow whole, washed down with water.

The recommended initial dose of the drug is 5 mg or 10 mg 1 time per day, both for patients who have not previously taken statins, and for patients who have been transferred to this drug after therapy with other HMG-CoA reductase inhibitors.

Choosing the initial dose of the drug, you should consider the level of cholesterol in each particular patient, as well as the possible risk of cardiovascular complications and the potential risk of side effects.

If necessary, after 4 weeks you can adjust the dose.

Due to the possible development of side effects when taking a dose of 40 mg compared with lower doses of the drug, the final titration to the 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 the target level of cholesterol was not reached when taking the dose of 20 mg, and which will be under medical supervision. At purpose of a dose of 40 mg careful observation of the doctor is recommended. The prescription of a dose 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.

- In renal failure In patients with mild to moderate severity, dose adjustment is not required. The recommended initial dose of the drug is 5 mg for patients with moderate renal insufficiency (CC less than 60 ml / minute). The appointment of Mertenil in any doses is contraindicated in patients with severe renal failure. In patients with moderate renal insufficiency, a dose of 40 mg is contraindicated.

- With hepatic insufficiency No increase in the systemic concentration of rosuvastatin in patients with a Child-Pugh score of 7 or lower was detected. However, an increase in the systemic concentration of the drug 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 patients taking the drug with a Child-Pugh score above 9. Patients with liver disease 8 of the active phase Mertenil is contraindicated.

- In ethnic groups. Patients of the Asian race may increase the systemic concentration of rosuvastatin. When prescribing doses of 10 and 20 mg, the recommended initial dose for Asian patients is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.

- With a predisposition to myopathy At prescribing doses of 10 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.

Proteinuria, mainly of tubular origin, was observed in patients when taking high doses of Mertenil, especially 40 mg, but in most cases was periodic or short-term. It is shown that such proteinuria does not mean the occurrence of acute or progression of existing kidney disease. The frequency of serious impairment of kidney function is increased when taking 40 mg of rosuvastatin. It is recommended to monitor indicators of renal function during drug therapy.

When using Mertenil in all dosages, and especially when taking the drug in a dose exceeding 20 mg, myalgia, myopathy and, in rare cases, rhabdomyolysis were detected. Very rarely did rhabdomyolysis occur while taking ezetimibe and HMG-CoA reductase inhibitors. In this case, the pharmacological interaction of the drugs cannot be excluded, therefore Mertenil and ezetimibe should be used with caution together.

Determination of CPK activity should not be carried out after intense physical exertion causing an increase in CPK, as this may make interpretation of results difficult. With an increase in CPK before therapy is more than 5 times higher than the upper limit of normal after 5-7 days, a repeated measurement should be carried out. If the repeated measurement confirms the baseline CPK (5 times higher than the upper limit of the norm), Mertenil therapy should not be started.

In patients who should prescribe the drug with caution (seesection "Contraindications") it is necessary to assess the ratio of the risk of the possible benefits of therapy and to carry out clinical observation throughout the course of therapy.

It is recommended to inform patients about the need to immediately report to the doctor about cases of sudden appearance of muscle pain, muscle weakness or spasms, especially in combination with indisposition or fever! In such patients, it is necessary to control the activity of CPK. Treatment should be stopped if the level of CPK is more than 5 times higher than the upper limit of normal or if the muscle symptoms are pronounced and cause daily discomfort throughout the day (even if the activity of CPK is 5 times less than the upper boundaries of the norm). If the symptoms disappear and the activity of CPK returns to normal, consideration should be given to the reappointment of Mertenil or the appointment of an alternative inhibitor of HMG-CoA reductase in smaller doses with careful monitoring of the patient. Regular monitoring of CPK activity in patients with no symptoms of rhabdomyolysis is impractical.

However, an increase in the incidence of myositis and myopathy was detected in patients taking other HMG-CoA reductase inhibitors together with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid-lowering doses, antifungal agents, protease inhibitors and macrolide antibiotics.Gemfibrozil increases the risk of myopathy in combination with some inhibitors of HMG-CoA reductase. Therefore, the concomitant use of rosuvastatin and gemfibrozil is not recommended. The ratio of risk and potential benefit should be carefully evaluated when rosuvastatin is used together with fibrates or nicotinic acid in lipid-lowering doses (more than 1 g).

Mertenil should not be given to patients with acute, serious diseases suggesting myopathy or possible development of secondary renal failure (for example, sepsis, hypertension, surgery, trauma, metabolic syndrome, convulsions, endocrine disorders, electrolyte disorders).

Like other HMG-CoA reductase inhibitors, Mertenil should be used with extreme caution in patients who abuse alcohol or have a history of liver disease.

It is recommended to carry out the determination of liver function parameters before and 3 months after the start of treatment. If the activity of “liver” transaminases in the serum is 3 times higher than the upper limit of normal, you should stop taking Mertenil or reduce the dose taken. The frequency of pronounced abnormal liver function (associated mainly with an increase in the activity of "liver" transaminases), increases when taking 40 mg of the drug.

In patients with secondary hypercholesterolemia due to hypothyroidism, nephrotic syndrome, the treatment of the underlying disease should be carried out before starting treatment with Mertenil.

In the course of pharmacokinetic studies, an increase in the systemic concentration of rosuvastatin among patients of Asian origin was detected in comparison with the data obtained among patients - representatives of the European race.

Simultaneous administration of rosuvastatin with protease inhibitors is not recommended.

- Impact on the ability to drive motor vehicles and control mechanisms Research on the effect of Mertenil on the ability to drive a vehicle and use of technical means has not been conducted. However, based on the pharmacodynamic properties of the drug, it can be assumed that it should not have such an effect. However, when driving a vehicle or other mechanisms, it must be borne in mind that dizziness may occur during treatment.

- Cyclosporine While taking rosuvastatin and cyclosporine, AUC of rosuvastatin increased 7-fold compared with values ​​obtained from healthy ones. The combined use leads to an increase in the concentration of rosuvastatin in the blood plasma 11 times. With simultaneous administration of drugs, changes in the concentration of cyclosporine in the blood plasma were not detected.

- Vitamin K antagonists As with other HMG-CoA reductase inhibitors, initiation of rosuvastatin therapy or increasing the dose of the drug in patients receiving vitamin K antagonists (for example,warfarin or other coumarin anticoagulants) can lead to an increase in international normalized ratio (MHO). Canceling or lowering the dose of rosuvastatin may cause a decrease in MHO. In such cases, MHO should be monitored.

- Ezetimibe When taking rosuvastatin and ezetimibe at the same time, there is no change in the AUC or both drugs. However, the pharmacodynamic interaction of rosuvastatin and ezetimibe, which can cause undesirable effects, cannot be ruled out.

- Gemfibrozil and other lipid-lowering agents Simultaneous administration of rosuvastatin and gemfibrozil leads to a 2-fold increase in C max and AUC of rosuvastatin. Based on data from a study of specific interactions, a corresponding pharmacokinetic interaction with fenofibrates is not expected, but pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and nicotinic acid in lipid-lowering doses (1 g or more per day) while taking it with HMG-CoA reductase inhibitors increased the risk of myopathy, possibly due to the fact that they can cause myopathy and when in monotherapy. At the same time taking the drug with gemfibrozil and other lipid-lowering agents, the initial dose of Mertenil should not exceed 5 mg.

- Protease inhibitors. Although the exact mechanism of interaction is unknown, the simultaneous administration of rosuvastatin with protease inhibitors may lengthen the half-life of rosuvastatin.In a pharmacokinetic study, while taking 20 mg of rozuvastatin and a combined preparation containing two protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir), healthy volunteers showed an increase of 2 times AUC and 5 times the C max of rosuvastatin, respectively. Therefore, it is not recommended to simultaneously administer rosuvastatin and protease inhibitors when treating patients with HIV.

- Antacids The simultaneous intake of rosuvastatin and antacids in suspension containing aluminum or Magnesium hydroxide, can lead to a decrease in the concentration of rosuvastatin in the blood plasma by about 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

- Erythromycin Simultaneous administration of rosuvastatin and erythromycin can lead to a decrease in AU (0-1) of rosuvastatin by 20% and C max of rosuvastatin by 30%. This relationship may be caused by increased intestinal motility, caused by taking erythromycin.

- Oral contraceptives / hormone replacement therapy Simultaneous intake of rosuvastatin and oral contraceptives can lead to an increase in AUC of ethinyl estradiol and norgestrel by 26% and 34%, respectively. Such an increase in plasma concentrations should be considered when choosing a dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement drugs are not available, therefore, a similar effect cannot be ruled out when using this combination. However, this combination of drugs was widely used by women during clinical trials and was well tolerated.

- Other drugs. No clinically significant interaction is expected while taking rosuvastatin and Digoxin .

- Cytochrome P450 isoenzymes The results of 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 fairly weak substrate for these enzymes. There was no clinically significant interaction between rosuvastatin and Fluconazole (an inhibitor of CYP2C9 and CYP3A4 isoenzymes) or Ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes). The combined use of itraconazole (an inhibitor of the isoenzyme CYP3A4) and rosuvastatin increases the AUC of rosuvastatin by 28% (clinically insignificant). Therefore, any interaction of drugs associated with the metabolism of cytochrome P450 is not expected.

- Symptoms: increased side effects.
- Treatment: There is no specific treatment for overdose. In case of overdose, symptomatic treatment and supportive measures are recommended. Liver function and degree of CPK activity should be monitored. Hemodialysis in this case is probably ineffective.

- Store in a dry, dark place at a temperature not exceeding 30 ° C.
- Keep out of reach of children.
- Do not use after expiration date.

Merten