Mertenil coated pills 10mg N30
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Active ingredients
Rosuvastatin
Release form
Pills
Composition
Active ingredient: Rosuvastatin (Rosuvastatin). Concentration of active ingredient (mg): 10
Pharmacological effect
Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutary coenzyme 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 cholesterol, HDL cholesterol, cholesterol-VLDL, TG-VLDL and increases the level of apolipoprotein AI (ApoA-1). Rozuvastatin reduces the ratio of LDL-LDL / HDL-C, total cholesterol / HS-HDL, cholesterol-LDL / cholesterol ApoB / ApoA 1. The therapeutic effect can be achieved within one weeks after the start of treatment, after 2 weeks, 90% of the maximum possible effect is achieved.In general, the maximum possible therapeutic effect is achieved after 4 weeks and is maintained with the further intake of the drug.
Pharmacokinetics
Absorption: the maximum plasma concentration of rosuvastatin is reached 5 hours after ingestion of the appropriate dose. Absolute bioavailability is approximately 20%. Distribution: Rosuvastatin is predominantly absorbed by the liver, which is the main site of cholesterol synthesis and clearance of cholesterol-LDL metabolism. The volume of distribution of rosuvastatin is approximately 134 liters. 90% of rosuvastatin binds to plasma proteins, mainly albumin. Metabolism: undergoes limited metabolism (approximately 10%). Rosuvastatin is a rather non-core substrate for metabolism by cytochrome P450 enzymes.CYP2C9 is the major isoenzyme involved in metabolism, while isoenzymes CYP2C19, CYP3A4 and CYP2D6 are less involved in metabolism. The main metabolite is N-desmethyl, which is 50% less active than rosuvastatin. Lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity on inhibition of circulating HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites. Excretion: approximately 90% of the dose of rosuvastatin is excreted unchanged from the body through the intestine (including absorbed and not absorbed rosuvastatin), and the rest is excreted unchanged by the kidneys. The half-life (T1 / 2) is 19 hours, does not change with increasing dose of the drug. The geometric mean plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other inhibitors of HMG-CoA reductase, membrane cholesterol transporter through the membranes, a transport protein C of organic anions, is involved in the hepatic capture of rosuvastatin. This carrier plays a major role in the removal of rosuvastatin by the liver. Linearity: the systemic exposure of rosuvastatin increases in proportion to the dose. Changes in pharmacokinetic parameters when taking the drug several times a day is not observed. Age and gender: sex and age do not have a clinically significant effect on the pharmacokinetic parameters of rosuvastatin. Ethnic groups: comparative studies of pharmacokinetics showed a twofold increase in the mean AUC (area under the concentration-time curve) and TCs (time to reach the maximum plasma concentration of the drug) in patients of Asian origin (Japanese, Chinese, Filipino, Vietnamese and Koreans) compared with the figures in the Caucasians. Indians had an excess of about 1.3 times the average AUC and Cmax. At the same time, the analysis of pharmacokinetics indicators for the entire studied population did not reveal clinically significant differences in the pharmacokinetics of the drug among representatives of the Caucasian, Negroid races, Latin Americans. Renal failure: in patients with mild to moderate renal failure, the plasma concentration of rosuvastatin or N-desmethyl metabolite does not change significantly. In patients with severe renal insufficiency (creatinine clearance (CC) less than 30 ml / min.a) the concentration of rosuvastatin in the blood plasma is 3 times higher, and the concentration of the N-desmethyl metabolite is 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in hemodialysis patients was about 50% higher than in healthy volunteers. Hepatic insufficiency: in patients with varying degrees of hepatic insufficiency with a score of 7 or less on the Child-Pugh scale, no increase in Rosuvastatin T10 was detected. However, in 2 patients with a score of 8 and 9 on the Child-Pugh scale, a T10 lengthening of about 2 times higher than the same indicator for patients with lower values on the Child-Pugh scale was observed. Experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is absent.
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 a supplement to diet therapy when dieting and other non-drug methods (eg, exercise, weight loss ) 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 this therapy is not effective enough.
Contraindications
Hypersensitivity to rosuvastatin or any of the components of the drug. Diseases of the liver 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). Myopathy. Simultaneous administration of cyclosporine. In patients predisposed to the development of myotoxic complications. Pregnancy. Lactation period. In women of childbearing age who do not use reliable contraception. 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: There is a risk of developing myopathyrabdomiolysis, 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.
Precautionary measures
For pills 5, 10 and 20 mg: The risk of myopathy / rhabdomyolysis is renal failure, hypothyroidism; a personal or family history of hereditary muscular diseases and a previous history of muscular toxicity using other HMG-CoA reductase inhibitors or fibrates; excessive drinking; conditions in which there is an increase in the plasma concentration of rosuvastatin; age over 70 years; history of liver disease; sepsis; hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or electrolyte disorders; uncontrolled epilepsy; race (Asian race); simultaneous reception of fibrates. For pills 40 mg: The risk of myopathy / rhabdomyolysis is renal failure, age over 70 years; history of liver disease; sepsis; hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or electrolyte disturbances, uncontrolled epilepsy.
Use during pregnancy and lactation
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. Data on the allocation of rosuvastatin with breast milk are not available. If necessary, the appointment of the drug during lactation breastfeeding should be stopped.
Dosage and administration
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. Prescribing a dose of 40 mg to patients who have not previously visited a doctor is not recommended! 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 of a 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. 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 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 for Asian patients is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients. With 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.
Side effects
On the part of the musculoskeletal system: an effect on skeletal muscle, causing myalgia, myopathy (including myositis) and, in rare cases, rhabdomyolysis with or without the development of acute renal failure, was observed in patients who took any dose of rosuvastatin, in particular a dose of more than 20 mg . An increase in CK content, depending on the dose taken, was found in patients taking rosuvastatin, but in most cases these manifestations were minor, asymptomatic and transient. If the content of CK is 5 times higher than VGN, the treatment should be stopped. On the part of the liver: as with the administration of other HMG-CoA reductase inhibitors, an increase in the activity of hepatic transaminases, depending on the dose taken, was detected in an insignificant number of patients taking rosuvastatin. However, in most cases, this increase was moderate, asymptomatic and transient. From the laboratory indicators: an increase in the concentration of glucose, bilirubin, GGT activity, ALP, impaired thyroid function indicators.
Overdose
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.
Interaction with other drugs
Cyclosporine: while taking rosuvastatin and cyclosporine, the AUC of rosuvastatin increased 7-fold compared with values obtained from healthy volunteers (see section “Contraindications”). 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, initiating rosuvastatin therapy or increasing the drug dose in patients receiving vitamin K antagonists (such as warfarin or other coumarin anticoagulants) can increase the international normalized ratio (MHO ). Canceling or lowering the dose of rosuvastatin may cause a decrease in MPE In such cases, MHO should be monitored. Ezetimibe: while taking rosuvastatin and ezetimibe at the same time, there is no change in the AUC or Cmax of both drugs. However, the pharmacodynamic interaction of rosuvastatin and ezetimibe, which can cause undesirable effects, cannot be ruled out. Gemfibrozil and other lipid-lowering drugs: the simultaneous use of rosuvastatin and gemfibrozil results in a 2-fold increase in Cmax and AUC of rosuvastatin (see the section "Special Instructions"). 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. Simultaneous intake of 40 mg of rosuvastatin and fibrates is contraindicated (see sections "Special instructions" and "Contraindications"). 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 rosuvastatin 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 (o-24) and 5 times Stach rosuvastatin, respectively. Therefore, it is not recommended to simultaneously administer rosuvastatin and protease inhibitors when treating patients with HIV.Antaiids: the concomitant use of rosuvastatin and antacids in a suspension containing aluminum or magnesium hydroxide may reduce the plasma concentration of rosuvastatin in the blood plasma by approximately 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: co-administration of rosuvastatin and erythromycin can lead to a decrease in AUQo-t) of rosuvastatin by 20% and Cum of rosuvastatin by 30%. This relationship may be caused by increased intestinal motility, caused by taking erythromycin. Oral contraceptives / hormone replacement therapy: co-administration 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 vitro and in vivo studies have shown 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.
special instructions
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 renal function increases when taking 40 mg of rosuvastatin.It is recommended to monitor indicators of renal function during therapy with Mertenil. 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, pharmacological interaction of drugs cannot be ruled out, therefore Mertenil and ezetimibe should be used with caution together (see the section "Interaction with Other Medicines"). The incidence of rhabdomyolysis when taking 40 mg of rosuvastatin increases. Determination of CPK activity should not be performed 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. Mertenil, like other HMG-CoA reductase inhibitors, should be used with extreme caution in patients with myopathy / rhabdomyolysis risk factors. These factors include: renal failure, hypothyroidism (for a dose of 40 mg, see the “Contraindications” section), personal or family history of muscular diseases (for a dose of 40 mg, see the “Contraindications” section), a history of mytoxicity while taking other inhibitors HMG-CoA reductase or fibrates (for a dose of 40 mg see section "Contraindications"), alcohol abuse (for a dose of 40 mg see section "Contraindications"), age over 70 years, conditions accompanied by an increase in plasma drug concentration ( see section “B Interaction of with other drugs ") (at a dose of 40 mg cm." Contraindications "), simultaneous fibrates (at a dose of 40 mg cm." Contraindications "). In such patients, the ratio of risk to potential benefit of therapy should be assessed and clinical observation should be carried out throughout the course of therapy.