Simvor - instructions for use, doses, side effects, contraindications

Composition:Each tablet contains
For a dosage of 10 mg
Active substance: simvastatin 10 mg
Excipients: lactose - 31.072 mg, pregelatinized starch 3.75 mg, microcrystalline cellulose 50 mg, low-substituted giprolase 4 mg, butyl hydroxy anisole 0.1 mg, magnesium stearate 1 mg.
Shell Material: opadray light pink OY-LS-54901 - 4 mg, water - q.s.
Fade light pink OY-LS-54901: hypromellose - 34,950%, lactose monohydrate - 27,180%, titanium dioxide - 25,207%, macrogol 400 - 9,700%. sodium citrate - 2.930%, iron oxide red - 0.033%.
For a dosage of 20 mg
Active substance: simvastatin 20 mg
Excipients: lactose 62.143 mg, pregelatinized starch 7.5 mg, microcrystalline cellulose 100 mg, low-added giprolose 8 mg, butyl hydroxy anisole 0.2 mg, magnesium stearate 2 mg.
Shell Material: opadraj brown OY-LS-56504 - 8 mg, water - q.s.
Fill brown OY-LS-56504: hypromellose - 34.950%, lactose monohydrate - 27.180%, titanium dioxide - 24.275%, macrogol 400 - 9.700%, sodium citrate - 2.930%. iron oxide yellow - 0.689%, iron oxide red - 0.276%.
For a dosage of 40 mg
Active substance: simvastatin 40 mg
Excipients: lactose 124.286 mg, pregelatinized starch 15 mg, microcrystalline cellulose 200 mg, low-substituted giprolose 16 mg, butyl hydroxy anisole 0.4 mg, magnesium stearate 4 mg.
Shell Material: opadrai pink OY-LS-54902 - 16 mg, water - q.s.
Opaprai pink OY-LS-54902: hypromellose 34.950%, lactose monohydrate 27.180%, titanium dioxide 23,990%, macrogol 400 9.700%, sodium citrate 2.930%, iron oxide red 1.250%.

Description:Tablets 5 mg: yellow biconvex tablets, oval in shape, covered with a film sheath with an engraved "SST" on one side and "5" on the other side.
Tablets 10 mg: pinkish-white biconvex oval tablet, film-coated with "SST" engraved on one side and "10" on the other side.
Tablets of 20 mg: light pink biconvex tablets - oval in shape, covered with a film sheath with an engraved "SST" on one side and "20" on the other side.
Tablets 40 mg: pink biconvex tablets of oval form, covered with a film shell with an engraving "SST" on one side and "40" on the other side.

Pharmacotherapeutic group:Hypolipidemic means - HMG-CoA reductase inhibitor.

ATX: & nbsp

C.10.A.A Inhibitors of HMG-CoA reductase

C.10.A.A.01 Simvastatin

Pharmacodynamics:A hypolipidemic agent obtained synthetically from the fermentation product of Aspergillus terreus is an inactive lactone in the body undergoing hydrolysis with the formation of a hydroxy-acid derivative.
The active metabolite inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), an enzyme that catalyzes the initial reaction of mevalonate formation from HMG-CoA. Since the conversion of HMG-CoA to mevalonate (an early stage in the synthesis of cholesterol, the use of simvastatin does not cause the accumulation of potentially toxic sterols in the body.) HMG-CoA is readily metabolized to acetyl-CoA, which participates in many synthesis processes in the body.Reduces the content of triglycerides (TG), low density lipoprotein (LDL), very low density lipoproteins (VLDL) and total cholesterol, in plasma (in cases of heterozygous familial and non-family forms of hypercholesterolemia, with mixed hyperlipidemia, when high cholesterol is a risk factor). Increases the high-density lipoprotein (HDL) content and reduces the ratio of LDL / HDL and total HDL cholesterol.
The onset of the effect is 2 weeks after the start of the treatment, the maximum therapeutic effect is achieved after 4-6 weeks. The action is preserved when the treatment is continued; When the therapy is stopped, the cholesterol content gradually returns to the initial level.

Pharmacokinetics:Absorption of simvastatin - high. After oral administration, the maximum concentration in the blood plasma is reached after approximately 1.3 -2.4 hours and decreases by 90% after 12 hours. The connection with plasma proteins is 95%.
Metabolized in the liver, has an effect of the first passage through the liver (hydrolyses to form an active derivative of beta-hydroxy acid, other active and also inactive metabolites are found).The half-life of active metabolites is 1.9 hours.
It is excreted mainly with feces (60%) in the form of metabolites. About 10% -15% is excreted by the kidneys in an inactive form.

Indications:Hypercholesterolemia
- Primary hypercholesterolemia (type IIa and IIb) with ineffectiveness of diet therapy with low cholesterol and other non-medicamentous measures (physical activity and weight loss) in patients with an increased risk of coronary atherosclerosis;
- combined hypercholesterolemia and hypertriglyceridemia, not corrected by a special diet and exercise.
Cardiac ischemia
- for the prevention of myocardial infarction, to reduce the risk of death, reduce the risk of cardiovascular disorders (stroke or transient ischemic attacks), slow the progression of coronary artery atherosclerosis, reduce the risk of revascularization procedures.

Contraindications:- Hypersensitivity to simvastatin or to other components of the drug, as well as to other drugs of the statin series (inhibitors of HMG-CoA reductase) in the anamnesis;
- liver disease in the active phase, persistent increase in the activity of "hepatic" enzymes of unclear etiology;
- diseases of skeletal muscles (myopathy);
- age under 18 years (effectiveness and safety not established);
- simultaneous application with powerful inhibitors of the isoenzyme CYP3A4 (voriconazole, itraconazole, ketoconazole, posaconazole, HIV protease inhibitors, boceprevirov, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, preparations containing the co-bicystate); simultaneous application with gemfibrozil, cyclosporin, danazol;
lactose intolerance;
- deficiency of lactase;
- Glucose-galactose malabsorption syndrome.

Carefully:With caution appoint the drug Symvor® under the following conditions:
- Alcohol abuse;
- after organ transplantation during immunosuppressant therapy (due to an increased risk of rhabdomyolysis and renal insufficiency);
- conditions that can lead to renal failure (arterial hypotension, severe infectious diseases, severe metabolic and endocrine disorders, water-electrolyte balance disorders, surgical interventions (including dental), or trauma;
- severe renal failure (creatinine clearance less than 30 ml / min.);
- decreased or increased tone of skeletal muscles of unclear etiology;
- epilepsy;
- simultaneous use with dronedarone (increased risk of myopathy and rhabdomyolysis).

Pregnancy and lactation:The drug Symvor® is contraindicated in pregnancy. There are several reports of anomalies in newborns whose mothers were taking simvastatin.
Women of childbearing age who receive simvastatin, should avoid conception.
If during pregnancy the pregnancy does occur, the Simvor® drug should be canceled, and the woman should be warned about the possible danger to the fetus. Data on the isolation of simvastatin with mother's milk are absent. If it is necessary to administer Symvor® during breastfeeding, it should be borne in mind that many drugs are excreted in breast milk and there is a threat of severe reactions, so breast-feeding during taking the drug is not recommended.

Dosing and Administration:Before starting treatment with Symvor®, the patient should be given a standard hypocholesterol diet, which should be observed throughout the course of treatment.
The drug Symvor® should be taken 1 time per day in the evening, with plenty of water.
The time of taking the drug does not depend on the food intake.
The recommended dose of Symvor® for the treatment of hypercholesterolemia varies from 5 to 80 mg 1 time per day in the evening. The recommended initial dose of the drug for patients with hypercholesterolemia is 10 mg. The maximum daily dose is 80 mg. Changes (selection) of the dose should be carried out at intervals of 4 weeks. In most patients, the optimal effect is achieved when taking the drug at doses up to 20 mg per day.
In patients with homozygous hereditary hypercholesterolemia, the recommended daily dose of Symvor® is 40 mg once a day in the evening or 80 mg in three divided doses (20 mg in the morning, 20 mg in the afternoon and 40 mg in the evening).
In the treatment of patients with coronary heart disease (CHD) or a high risk of developing coronary artery disease, the effective dose of the Simvor ® preparation is 20-40 mg per day. Therefore, the recommended initial dose in such patients is 20 mg per day. Changes (selection) of the dose should be carried out at intervals of 4 weeks, if necessary, the dose can be increased to 40 mg per day.
If the LDL content is less than 75 mg / dL (1.94 mmol / L), the total cholesterol content is less than 140 mg / dL (3.6 mmol / L),the dose of the drug should be reduced.
For patients taking simvastatin simultaneously diltiazem or ranolazine, the daily dose of simvastatin should not exceed 20 mg.
In elderly patients or with a mild or moderate renal failure, no dosage is required.
In patients with chronic renal failure (creatinine clearance less than 30 ml / min) or with simultaneous application of cyclosporine, danazol. fibrates (except fenofibrate) dronedarone, nicotinic acid as lipid-lowering doses (more than 1 g / day), the maximum recommended dose Simvor® drug should not exceed 10 mg per day.
The daily dose of Symvor® in patients taking concomitantly with it amiodarone or verapamil, should not exceed 20 mg.

Side effects:By frequency, side effects are divided according to criteria of the World Health Organization (WHO) for the following
categories: very often (≥ 1: 10); often (≥ 1: 100 and <1: 10); infrequently (≥ 1: 1000 and <1: 100); rarely (≥ 1: 10000 and <1: 1000); highly
rarely (<1: 10000), the frequency is unknown (the frequency can not be estimated from the available data).
Infringements from bodies of a hemopoiesis.
Rarely, anemia.
Disorders from the digestive system
Rarely - dyspepsia, nausea, diarrhea, vomiting, acute pancreatitis, hepatitis, cholestatic jaundice: very rarely - fatal and non-fatal hepatic insufficiency; the frequency is unknown - abdominal pain, constipation, flatulence, increased activity of "liver" transaminases, alkaline phosphatase and creatine phosphokinase.
Disorders from the nervous system and sensory organs
Rarely - dizziness, paresthesia, peripheral neuropathy; very rarely - insomnia, sleep disturbance, "nightmarish" dreams; frequency unknown - asthenic syndrome, headache, muscle cramps, blurred vision, impaired taste, memory loss, confusion, depression.
Allergic and immunopathological reactions
Rarely, hypersensitivity syndrome (angioedema, rheumatic polymyalgia, vasculitis, thrombocytopenia,
increased ESR, fever, arthritis, urticaria, photosensitization, "hot flushes" of the blood to the skin of the face, dyspnea, lupus-like syndrome, eosinophilia, dyspnea, general weakness); very rarely - immuno-mediated necrotizing myopathy.
Disturbances from the skin
Rarely - skin rash, itching, alopecia; frequency unknown - dermatomyositis.
Disorders from the musculoskeletal system
Rarely - myopathy, myalgia, muscle cramps, rhabdomyolysis; frequency unknown - muscle weakness, myositis, tendinopathy, tendon rupture.
Disturbances from the respiratory system
The frequency is unknown - the interstitial disease of the lungs.
Disorders from the excretory system
The frequency is unknown - acute renal failure. Myoglobinuria.
Disorders from the reproductive system
The frequency is unknown - erectile dysfunction.
Violations from laboratory indicators
Rarely, an increase in glycosylated hemoglobin *, an increase in the level of glucose in the blood plasma, an increase in the activity of gamma-glutamyltransferase.
Other violations
The frequency is unknown - malaise.
* should be considered when diagnosing type II diabetes.

Overdose:In none of the known few cases of overdose (the maximum dose of 450 mg) specific symptoms were identified.
Treatment: induce vomiting, take Activated carbon. Symptomatic therapy.It is necessary to monitor the liver and kidney function, the level of CK in the blood serum. With the development of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), stop taking the drug immediately and inject the patient with a diuretic and sodium bicarbonate (intravenous infusion). If necessary, hemodialysis is indicated.
Rhabdomyolysis can cause hyperkalemia, which can be eliminated by intravenous calcium supplementation with calcium gluconate, glucose infusion with insulin, use of potassium ion exchangers, or in severe cases by hemodialysis.

Interaction:Powerful inhibitors of the isoenzyme CYP3A4. Simvastatin is metabolized by the CYP3A4 isoenzyme, but does not inhibit the activity of this isoenzyme. This suggests that the use of simvastatin does not affect the concentration in the blood plasma of drugs metabolized by the isozyme CYP3A4. Powerful inhibitors of the CYP3A4 isoenzyme increase the risk of myopathy by decreasing the rate of simvastatin clearance. Simultaneous use of potent inhibitors of the isoenzyme CYP3A4 (eg, itraconazole, ketoconazole,pozakonazola, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, drugs containing the co-bicystate) and simvastatin is contraindicated.
Other agents that can cause the development of myopathy
The risk of developing myopathy increases with the co-administration of other lipid-lowering drugs that are not potent inhibitors of the CYP3A4 isoenzyme, but are capable of causing myopathy under monotherapy, such as gemfibrozil and other fibrates (except fenofibrate), a nicotinic acid in lipid-lowering doses (more than 1 g per day). The risk of myopathy increases with the simultaneous use of danazol and cyclosporine. The simultaneous use with gemfibrozilom, danazolom, cyclosporine is contraindicated.
The risk of developing myopathy increases with simultaneous use of simvastatin with amiodarone, verapamil, amlodipine, and lopitamide. The risk of myopathy is slightly increased in patients receiving diltiazem simultaneously with simvastatinom in a dose of 80 mg.
It is necessary to reduce the dose of simvastatin with simultaneous use with amiodarone, verapamil, amlodipine, diltiazem.
Moderate inhibitors of the isoenzyme CYP3A4. With the simultaneous use of dronedarone, ranolazine simultaneously with high doses of simvastatin, the risk of myopathy may increase. In this regard, it is necessary to reduce the dose of simvastatin when used simultaneously with dronedarone and ranolazine.
Grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme and can increase the concentration in the blood plasma of agents metabolized by the CYP3A4 isoenzyme.
An increase in the activity of HMG-CoA reductase inhibitors after consuming 250 ml of juice per day is minimal and has no clinical significance. However, consumption of a large amount of juice (more than 1 liter per day) with the use of simvastatin significantly increases the level of inhibitory activity against HMG in blood plasma. In this regard, it is necessary CoA-reductase to avoid the consumption of grapefruit juice in large quantities.
With the simultaneous use of simvastatin with fusidic acid, the risk of myopathy may increase. Simultaneous application of transport protein inhibitors OATP1B1 and simvastatin may lead to an increase in the plasma concentration of the hydroxy acid of simvastatin and an increased risk of myopathy.
With simultaneous use with colchicine in patients with renal insufficiency, cases of myopathy and rhabdomyolysis have been described. When combined therapy with these drugs, such patients should be carefully monitored. Simvastatin potentiates the effect of oral anticoagulants (eg fenprokumone, warfarin) and increases the risk of bleeding, which requires monitoring of blood coagulation rates before treatment, and often enough in the initial period of therapy. After achieving a stable prothrombin time or INR (international normalized ratio), further monitoring should be performed at intervals recommended for patients receiving anticoagulant therapy. When changing the dosage or stopping the intake of simvastatin, it is also necessary to monitor prothrombin time or INR according to the above scheme.
Therapy with simvastatin does not cause changes in prothrombin time and the risk of bleeding in patients who do not take anticoagulants. With simultaneous application simvastatin increases the level of digoxin in the blood plasma. Kolestyramine and colestipol reduce the bioavailability of simvastatin.
The use of simvastatin is possible 4 hours after the administration of these drugs, with an additive syndrome noted.

Special instructions:At the beginning of therapy with Simvor®, a progressive increase in the activity of "hepatic" enzymes is possible.
Before the beginning of therapy and further regularly monitor the activity of "liver" enzymes: every 6 weeks for the first 3 months, then every 8 weeks for the remainder of the first year, and then 1 time in six months, as well as with increasing doses. When the dose is raised to 80 mg, this test should be performed every 3 months. With a stable triple increase in the activity of transaminases, the preparation of Symvor® should be discontinued.
There are rare post-registration reports of cases of liver failure, including fatal. If serious damage to the liver develops with the Simvor® drug, Simvor® should be discontinued immediately. If there is no other cause of the development of liver damage, the repeated administration of Symvor® is contraindicated.The cause of increased activity of alanine aminotransferase (ALT) can also be damage to muscle tissue, so the increase in activity of ALT and CK may indicate the development of myopathy. The abolition of lipid-lowering drugs during pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.
Due to the fact that inhibitors of HMG-CoA reductase inhibitors inhibit the synthesis of cholesterol, and cholesterol and other products of its synthesis play an essential role in fetal development, including steroids and synthesis of cellular membranes, simvastatin may have an adverse effect on the fetus when prescribing it to pregnant women (women of reproductive age should avoid conception). If during pregnancy pregnancy is established, the drug should be canceled, and the woman herself is warned about possible danger to the fetus. The use of Symvor® is not recommended in women of childbearing age who do not use contraceptives. In patients with a reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome), with increasing cholesterol concentration, first treatment of the underlying disease that causes hypercholesterolemia should be performed.Cigarette preparation with caution is prescribed for patients who abuse alcohol and / or have a history of liver disease.
Before and during treatment, the patient should be on a hypocholesterol diet. Simultaneous reception of grapefruit juice can increase the severity of side effects associated with taking the drug Symvor®, so you should avoid them at the same time. The preparation Symvor®, like other inhibitors of HMG-CoA reductase, should not be used at an increased risk of rhabdomyolysis (against severe acute infection, arterial hypotension, planned large surgery, trauma, severe metabolic disorders). In patients with myalgia, myasthenia gravis and / or marked increase in the activity of CKK, treatment with the drug is stopped. The drug Symvor ® is not indicated in cases where there is hypertriglyceridemia I, IV and V types. Treatment with Symvor® can cause myopathy, which leads to rhabdomyolysis.
Rhabdomyolysis is a dangerous condition that can lead to kidney failure and death. The risk of this pathology increases in patients,receiving simultaneously with the drug Symvor® one or more of the following medicines: fibrates (fenofibrate), ciclosporin, nefazadone, macrolides (erythromycin, clarithromycin, telithromycin), antifungal agents from the azole group (ketoconazole, itraconazole, voriconazole), HIV protease inhibitors (ritonavir), boceprevir, telaprevir, danazol, blockers of "slow" calcium channels (verapamil, diltiazem. amlodipine), lomitapid, ranolazine, amiodarone, dronedaron. fusidic acid, a nicotinic acid in lipid-lowering doses (more than 1 g / day), preparations containing a cobicystate, colchicine. The risk of myopathy is also increased in patients with severe renal failure.
Simultaneous use of simvastatin and fusidic acid is not recommended.
If the use of systemic fusidic acid preparations is considered necessary, simvastatin should be canceled for the period of this therapy. In exceptional cases, when long-term therapy with systemic fusidic acid preparations is necessary, for example, for the treatment of severe infections,the possibility of simultaneous use of simvastatin and fusidic acid should be considered individually in each individual case and combined therapy should be performed under careful medical supervision.
All patients starting Symov® therapy, as well as patients who need to increase the dose of the drug, should be warned about the possibility of myopathy and the need for immediate medical attention in the event of unexplained pain, muscle soreness, lethargy or muscle weakness, especially if it is accompanied by malaise or fever. The drug should be discontinued immediately if myopathy is diagnosed or suspected.
In order to diagnose the development of myopathy, it is recommended to regularly measure the activity of CK. In the treatment with Symvor®, the activity of serum CK can increase, which should be taken into account in the differential diagnosis of chest pain. The criterion for the discontinuation of the drug is an increase in the activity of CK in the blood serum more than 10 times the upper limit of the norm.
Symvor® is effective both in the form of monotherapy, and in combination with bile acid sequestrants. If the current dose is skipped, the drug should be taken as soon as possible. If it's time to take the next dose, do not double the dose.
Patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) are treated with caution under the control of kidney function. Duration of the drug is determined individually by the attending physician.

Effect on the ability to drive transp. cf. and fur:The adverse effect of Simvor® on the ability to drive and work with machinery has not been reported.

Form release / dosage:The coated tablets are 5 mg, 10 mg, 20 mg, 40 mg.

Packaging:10 tablets in a blister of aluminum foil and PVC film.
1, 3 or 10 blisters with instructions for use in a cardboard bundle.

Storage conditions:Store in a dry place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011797

Date of registration:07.10.2011 / 06.06.2016

Expiration Date:Unlimited

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp2016-12-27

Illustrated instructions

Instructions

Simvore® (Simvor®)