Mertenil - instructions for use, analogs, reviews and release forms (5 mg, 10 mg, 20 mg and 40 mg tablets) of the statin drug for the treatment of hypercholesterolemia and cholesterol reduction in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Deadlyl. There are reviews of visitors to the site - consumers of this statin drug, as well as the opinions of doctors of specialists on the use of the martenil in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues Mertenila with existing structural analogues.Use to treat atherosclerosis, hypercholesterolemia, and lower cholesterol in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

Deadlyl - a hypolipidemic drug. Rosuvastatin (the active substance of the drug, Mertenil) is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutarylcoenzyme A into mevalonate, which is a precursor to cholesterol. The main target of rosuvastatin is the liver, where the synthesis of cholesterol (Xs) and catabolism of LDL.

Mertenil increases the number of LDL receptors on the surface of hepatocytes, increasing the uptake and catabolism of LDL.

It also inhibits the synthesis of Xc-VLDL in liver cells, thereby reducing the total content of LDL and VLDL. Methenyl reduces the elevated levels of LDL-C, total Xc and triglycerides (TG), increases the level of X-HDL, and also reduces the content of apolipoprotein B (ApoB), Xc-non-HDL (total cholesterol minus cholesterol, HDL cholesterol, -VLDL) and increases the level of apolipoprotein A-1 (ApoA-1).Rosuvastatin reduces the ratio of Xc-LDL / Xc-HDL, total Xc / Xc-HDL, Xc-non-HDL / Xc-HDL and ApoB / ApoA-1.

The therapeutic effect can be achieved 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.

Studies on the effect of the Mertenil on reducing the number of complications caused by lipid disorders, such as ischemic disease, have not yet been completed.

Composition

Calcium rosuvastatin + excipients.

Pharmacokinetics

Cmax rosuvastatin in blood plasma is achieved 5 hours after ingestion of the appropriate dose. Absolute bioavailability is approximately 20%. The systemic exposure of rosuvastatin increases in proportion to the dose. Changes in pharmacokinetic parameters when taking the drug several times a day are not noted. 90% of rosuvastatin binds to plasma proteins, mainly albumin. Metabolized mainly in the liver, which is the main site for the synthesis of Xc and the clearance of X-LDL metabolism.It is subject to limited metabolism (about 10%). Approximately 90% of the administered dose of rosuvastatin is excreted unchanged from the body through the intestine (including absorbed and unabsorbed rosuvastatin), and the remainder is excreted unchanged by the kidneys.

Age and gender do not have a clinically significant effect on the pharmacokinetic parameters of rosuvastatin.

Indications

• hypercholesterolemia and combined (mixed) dyslipidemic states to reduce the elevated concentrations of total cholesterol, LDL-C, apolipoprotein B and TG in the blood serum as a supplement to diet therapy, when diet and other non-drug methods (eg exercise, weight loss) are insufficient ;
• family homozygous hypercholesterolemia as a supplement to diet therapy and other methods of lipid lowering therapy (eg, LDL-apheresis) or in cases when such therapy is not effective enough;
• hypertriglyceridemia (type 4 by Fredrickson) as a supplement to the diet;
• to slow the progression of atherosclerosis as a supplement to the diet in patients who are shown therapy to reduce the concentration of total Xc and Xc-LDL;
• Primary prevention of major cardiovascular complications (cardiovascular death, stroke, heart attack, unstable angina and arterial revascularization) in adult patients without clinical signs of coronary artery disease, but with an increased risk of its development (age over 50 for men and over 60 for women , elevated C-reactive protein concentration (> 2 mg / L) with at least one of additional risk factors, such as hypertension, low concentration of HDL-C, smoking, family history of early on ala CHD).

Forms of release

Tablets coated with 5 mg, 10 mg, 20 mg and 40 mg.

Instructions for use and dosage

Before starting treatment, the patient should follow a standard diet with low cholesterol foods, which should continue throughout the treatment period. 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 levels of lipids.

The drug is taken orally, at any time of the day, regardless of food intake.Tablets should not be chewed and crushed, they must be swallowed whole, washed down with water.

The recommended initial dose of the drug is 5 mg or 10 mg once a day for both patients who did not previously take statins, and for patients transferred to receive this drug after treatment with other inhibitors of HMG-CoA reductase.

Choosing the initial dose of the drug, you should consider the level of Xc 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 do a dose adjustment.

In connection with the possible development of side effects when taking a dose of 40 mg compared with lower doses of the drug, the final titration to a maximum dose of 40 mg should be performed only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia), in whom a dose of 20 mg did not achieve the target cholesterol level, and which will be under medical supervision.When appointing a dose of 40 mg, a thorough observation of the doctor is recommended. Do not administer a dose of 40 mg to patients who have not previously consulted a doctor.

The recommended initial dose for elderly patients (over 70 years) is 5 mg.

In patients with mild or moderate renal insufficiency, 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 / min). Patients with renal insufficiency of moderate severity of the appointment of the drug in a dose of 40 mg is contraindicated. The administration of the drug Mertenil in any dose is contraindicated in patients with severe renal insufficiency.

Patients with hepatic insufficiency of 7 and lower on the Child-Pugh scale did not show an increase in the systemic concentration of rosuvastatin. However, in patients with hepatic insufficiency of 8 and 9 on the Child-Pugh scale, an increase in the systemic drug concentration was noted. These patients should be monitored for liver function against therapy. Data on the use of rosuvastatin in patients with hepatic insufficiency of more than 9 points on the Child-Pugh scale are absent. Patients with liver disease in the active phase of Mortenil is contraindicated.

When administered at doses of 10 mg 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 in such patients is contraindicated.

Rosuvastatin binds to various transport proteins (in particular, to OATP1B1 and BCRP). When combined with medicinal products (such as cyclosporin, some HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and / or tipranavir), the risk of myopathy (including rhabdomyolysis may increase the concentration of rosuvastatin in plasma by interaction with transport proteins) ). In such cases, the possibility of prescribing alternative therapy or temporarily stopping the drug Mertenil should be evaluated. If the use of the above drugs is necessary, the ratio of benefit and risk of concomitant therapy with Mertenil should be assessed and the possibility of reducing its dose should be considered.

Side effect

• thrombocytopenia;
• hypersensitivity reactions, including angioedema;
• type 2 diabetes mellitus;
• depression;
• dizziness;
• headache;
• polyneuropathy;
• memory loss;
• sleep disorders (including insomnia and nightmares);
• cough;
• dyspnea;
• constipation, diarrhea;
• stomach ache;
• nausea;
• pancreatitis;
• increased activity of hepatic transaminases;
• jaundice;
• hepatitis;
• itching;
• rash;
• hives;
• Stevens-Johnson syndrome;
• myalgia;
• myopathy (including myositis);
• rhabdomyolysis;
• arthralgia;
• immuno-mediated necrotizing myopathy;
• hematuria (blood in the urine);
• proteinuria;
• gynecomastia;
• sexual dysfunction;
• asthenic syndrome;
• peripheral edema.

Contraindications

For tablets 5 mg, 10 mg and 20 mg

• liver diseases in the active phase, including a persistent increase in hepatic transaminase activity, as well as any increase in serum transaminase activity by more than 3 times compared with VGN;
• hepatic failure (more than 9 on the Child-Pugh scale);
• severe renal dysfunction (KK less than 30 ml / min);
• 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 means of contraception;
• age under 18 years (effectiveness and safety not established);
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption;
• increased sensitivity to rosuvastatin and other components of the drug.

For tablets 40 mg

• liver diseases in the active phase, including a persistent increase in hepatic transaminase activity, as well as any increase in serum transaminase activity by more than 3 times compared with VGN;
• hepatic failure (more than 9 on the Child-Pugh scale);
• renal failure of moderate severity (CC less than 60 ml / min);
• hypothyroidism;
• myopathy;
• personal or family anamnesis of muscular diseases;
• myotoxicity on the background of taking other inhibitors of HMG-CoA reductase or fibrates in anamnesis;
• in patients predisposed to the development of myotoxic complications;
• simultaneous administration of cyclosporine;
• simultaneous reception of fibrates;
• excessive use of alcohol;
• conditions that may lead to an increase in the concentration of rosuvastatin in the blood plasma;
• pregnancy;
• lactation period;
• age under 18 years (effectiveness and safety not established);
• patients of the Mongoloid race;
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption;
• increased sensitivity to rosuvastatin and other components of the drug.

Application in pregnancy and lactation

Mertenil is contraindicated in pregnancy and lactation.

Women of childbearing age should use reliable and adequate contraception.

Since cholesterol and Xs biosynthesis products are of great importance for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of its use in pregnancy.

In case of pregnancy, the drug should be stopped immediately.

Data on the isolation of the drug with breast milk are absent. If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Use in children

Currently, Mertenil is not recommended for use in children and adolescents under the age of 18 (efficacy and safety for this age group of patients not established).

Application in elderly patients

The recommended initial dose for elderly patients (over 70 years) is 5 mg.

special instructions

Influence on the kidneys

Proteinuria, mainly of tubular origin, was noted in patients receiving the drug Mertenil in high doses, especially at a dose of 40 mg, but in most cases it was periodic or short-term. It is shown that such proteinuria does not mean the emergence of acute or progressive disease of the existing kidney disease. The frequency of severe renal dysfunction increases with the use of rosuvastatin 40 mg. It is recommended to monitor the parameters of kidney function during therapy with the drug Mertenil.

Musculoskeletal system

With the use of the drug Mertenil in all doses, especially when taking the drug at a dose of more than 20 mg, revealed myalgia, myopathy and, in rare cases, rhabdomyolysis. Very rarely there was rhabdomyolysis with simultaneous administration of ezetimibe and inhibitors of HMG-CoA reductase. In this case, pharmacological interaction of the drugs can not be ruled out, therefore, both Herethenim and ezetimibe should be used with caution.

The incidence of rhabdomyolysis with rosuvastatin 40 mg is increasing.

Definition of CKF

Determination of the activity of CKD should not be performed after intensive physical exertion causing an increase in CK, as this may make interpretation of the results difficult. With an increase in the CKK value before the start of therapy, more than 5 times higher than ULN, after 5-7 days, a second measurement should be performed. If the re-measurement confirms the baseline CK (5-fold higher compared with UGN), therapy with Mertenil should not be started.

Before the start of therapy

The drug Mertenil, like other inhibitors of HMG-CoA reductase, should be used with extreme caution in patients with existing risk factors for myopathy / rhabdomyolysis. Such factors include:

• kidney failure;
• hypothyroidism (for a dose of 40 mg);
• personal or family anamnesis of muscle diseases (for a dose of 40 mg);
• presence in the anamnesis of myotoxicity on the background of taking other inhibitors of HMG-CoA reductase or fibrates (for a dose of 40 mg);
• alcohol abuse (for a dose of 40 mg);
• age over 65;
• states, accompanied by an increase in the concentration of the drug in the blood plasma (for a dose of 40 mg);
• simultaneous reception of fibrates (for a dose of 40 mg).

In such patients, the risk-to-benefit ratio of therapy should be assessed and clinical observation performed throughout the course of therapy.

During therapy

It is recommended that patients be informed of the need to report promptly to the doctor about cases of unexpected muscle pain, muscle weakness, or spasms, especially in combination with malaise or fever.

In such patients, it is necessary to monitor the activity of CK. Treatment should be discontinued if the level of CK is more than 5 times higher than ULN, or if muscle symptoms are severe and cause daily discomfort throughout the day (even if the activity of CK is 5 times less than ULN). If symptoms disappear and CPK activity returns to normal, consideration should be given to the re-administration of the drug, Mertenil, or the administration of an alternative inhibitor of HMG-CoA reductase in smaller doses, with careful monitoring of the patient. Regular monitoring of the activity of CK in patients with no symptoms of rhabdomyolysis is inexpedient.

Very rare cases of immuno-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of proximal muscles and increased activity of CKK in blood serum during treatment or with stopping of taking statins are noted. rosuvastatin.It may be necessary to conduct additional studies of the muscular and nervous system, serological studies, as well as therapy with immunosuppressive drugs.

However, an increase in the incidence of myositis and myopathy was found in patients taking other HMG-CoA reductase inhibitors in conjunction with fibrolic acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid-lowering doses, antifungal agents, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Therefore, simultaneous administration of rosuvastatin and gemfibrozil is not recommended. The risk-to-benefit ratio should be carefully evaluated when rosuvastatin is combined with fibrates or nicotinic acid in lipid-lowering doses (> 1 g). Contraindicated simultaneous administration of rosuvastatin in a dose of 40 mg and fibrates.

The drug Mortenil should not be prescribed to patients with acute, severe illnesses suggesting myopathy or with the possible development of secondary renal failure (eg, sepsis, hypertension,surgical intervention, trauma, metabolic syndrome, convulsions, endocrine disorders, electrolyte disorders.

Effects on the liver

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

It is recommended to perform the determination of liver function indicators before and after 3 months after the start of treatment. If the activity of hepatic transaminases in the blood serum is 3 times higher than UGN, stop taking the drug or reduce the dose taken. The frequency of pronounced violations of the liver (associated mainly with an increase in the activity of hepatic transaminases), increases with the intake of 40 mg of the drug.

Secondary hypercholesterolemia

In patients with secondary hypercholesterolemia due to hypothyroidism, nephrotic syndrome, therapy of the underlying disease should be performed prior to the initiation of treatment with the drug Mertenil.

Ethnic groups

In the course of pharmacokinetic studies, an increase in the systemic concentration of rosuvastatin among patients of Asian origin was found,obtained among patients - representatives of the Caucasoid race.

Inhibitors of proteases

Simultaneous administration of rosuvastatin with protease inhibitors is not recommended.

Lactose

The drug should not be used in patients with lactase deficiency, intolerance to galactose and glucose-galactose malabsorption.

Interstitial lung disease

With the use of some statins, especially for a long time, there have been reports of single cases of interstitial lung disease. Manifestations of the disease can be shortness of breath, unproductive cough and deterioration in overall health (weakness, weight loss and fever). If suspicion of interstitial lung disease should be stopped by statin therapy.

Diabetes mellitus type 2

There is evidence that statins, like a class, cause an increase in blood glucose and in some patients at high risk of diabetes in the future can provoke a level of hyperglycemia, which shows the standard treatment of diabetes mellitus. However, this risk is outweighed by a reduced risk of developing vascular complications, so there is no reason to stop treatment with statins.In patients at risk for hyperglycemia (fasting glucose from 5.6 to 6.9 mmol / L, BMI greater than 30 kg / m2, elevated triglyceride concentration, hypertension), clinical and biochemical indicators should be monitored in accordance with national guidelines.

Impact on the ability to drive vehicles and manage mechanisms

Studies to study the influence of the drug Mertenil on the ability to drive a vehicle and use of technical means were not conducted. Care should be taken when driving a motor vehicle or work that requires a high concentration of attention and speed of psychomotor reactions (dizziness may occur during therapy).

Drug Interactions

Effect of the use of other drugs on Mertenil

Rosuvastatin binds to some transport proteins, in particular, to OATP1B1 and BCRP. The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of myopathy.

With concomitant administration of rosuvastatin and cyclosporin AUC, rosuvastatin increased 7-fold compared with the values ​​obtained in healthy volunteers. Joint application leads to an increase in the concentration of rosuvastatin in blood plasma by 11 times. With simultaneous administration of drugs, changes in the concentration of cyclosporine in the blood plasma were not detected.

The simultaneous administration of rosuvastatin and gemfibrozil or other means of lowering the level of lipids leads to an increase in 2 times of Cmax and AUC of rosuvastatin.

Based on the data of the specific interaction, no 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) with simultaneous administration with HMG-CoA reductase inhibitors increased the risk of myopathy, possibly due to the fact that they can cause myopathy and on admission in monotherapy. The simultaneous administration of rosuvastatin in a dose of 40 mg and fibrates is contraindicated. With the simultaneous administration of the drug with gemfibrozilom and other lipid-lowering agents, the initial dose of the drug Mortenil should not exceed 5 mg.

The simultaneous use of rosuvastatin 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in rosuvastatin AUC in patients with hypercholesterolemia. It is impossible to exclude an increased risk of side effects due to the pharmacodynamic interaction between rosuvastatin and ezetimibe.

Although the exact mechanism of interaction is unknown, simultaneous administration of rosuvastatin with protease inhibitors may lead to an elongation of T1 / 2 rosuvastatin. In a pharmacokinetic study with simultaneous administration of rosuvastatin at a dose of 20 mg and a combined preparation containing two protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir), healthy volunteers showed a 2-fold increase in AUC (0-24) and 5 times the C max of rosuvastatin, respectively. Therefore, simultaneous administration of rosuvastatin and protease inhibitors in the treatment of patients with HIV is not recommended.

Simultaneous administration of rosuvastatin and antacids in a suspension containing aluminum or magnesium hydroxide can lead to a decrease in the concentration of rosuvastatin in the blood plasma by approximately 50%. This action is less pronounced if antacids are administered 2 hours after rosuvastatin administration.The clinical significance of this interaction has not been studied.

Simultaneous administration of rosuvastatin and Erythromycin can lead to a decrease in AUC (0-t) rosuvastatin by 20% and Cmax rosuvastatin - by 30%. This relationship can be caused by increased intestinal motility caused by the intake of erythromycin.

The results of the studies showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a rather weak substrate for these enzymes. There was no clinically significant interaction between rosuvastatin and Fluconazole (inhibitor of isoenzymes CYP2C9 and CYP3A4) or Ketoconazole (inhibitor of isoenzymes CYP2A6 and CYP3A4). The combined use of Itraconazole (inhibitor of the isoenzyme CYP3A4) and rosuvastatin increases the aUC of rosuvastatin by 28% (clinically insignificant). Therefore, any interaction of drugs associated with metabolism involving cytochrome P450 isoenzymes is not expected.

Interaction with drugs that requires dose adjustment

The dose of Medenil should be adjusted when it is necessary to use it together with drugs that increase the exposure of rosuvastatin.If the exposure is expected to be 2 times or more, the initial dose of the drug Mortenil should be 5 mg once a day. Also, the maximum daily dose of the drug Mertenil should be adjusted so that the expected exposure of rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of medications interacting with rosuvastatin. For example, the maximum daily dose of the drug Mortenil with simultaneous use with gemfibrozil is 20 mg (1.9 times increase in exposure), with ritonavir / atazanavir 10 mg (an increase in exposure by 3.1 times).

Influence of the use of morbenil on other drugs

As with other HMG-CoA reductase inhibitors, initiating rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (eg, Warfarin or other coumarin anticoagulants) may lead to an increase in MHO. Cancellation or reduction of the dose of rosuvastatin may cause a decrease in MHO. In such cases, MHO monitoring should be carried out.

Simultaneous administration of Mbhartenil and oral contraceptives may increase the AUC of ethinylestradiol and norgestrel by 26% and 34%, respectively,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 therapy are not available, therefore, it is impossible to exclude a similar effect when using this combination. However, this combination of drugs was widely used by women during clinical trials and was well tolerated.

No clinically significant interaction is expected with simultaneous administration of rosuvastatin and digoxin.

Analogues of the drug Menlenil

Structural analogs for the active substance:

• Akorta;
• The Cross;
• Ro-statin;
• Rosart;
• Rosystark;
• Rosuvastatin;
• Rosewood;
• Rosulip;
• Roxer;
• Rustor;
• Suvardio;
• Tevastor.

Analogues for the pharmacological group (statins):

• Aktalipid;
• Anistat;
• Apexstatin;
• Atherostat;
• Atokord;
• Atomax;
• Ator;
• Atorvastatin;
• Atorvox;
• Atoris;
• The Vasator;
• Vazilip;
• Zocor;
• Zokor forte;
• Zorstat;
• Cardiostatin;
• Leskol;
• Leskol Fort;
• Lipobay;
• Lipon;
• Lipostat;
• Lipofford;
• Liprimar;
• Liptonorm;
• Lovacor;
• Lovastatin;
• Lovasterol;
• Mevakor;
• Medostatin;
• Novostat;
• Ovenkor;
• Pravastatin;
• Rovacor;
• Simvakol;
• Simvale;
• Simvastatin;
• Simvastol;
• Symvor;
• Simgal;
• Simlo;
• Sinquard;
• Torvazine;
• Torvacard;
• Torvalip;
• Torvas;
• Tulip;
• Holvasim;
• Holletar.

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