Simvastatin-Teva - instructions for use, dose, side effects, contraindications

lactose monohydrate, corn pregelatinized starch, microcrystalline cellulose, ascorbic acid, citric acid monohydrate, butylhydroxyanisole, magnesium stearate;

Shell

Tablets coated with a film coating, 10 mg:

Opadry II 33G23092 (peach) (hypromellose (E464), titanium dioxide (E171), lactose monohydrate, macrogol-3000, triacetin, dye iron oxide red (E172), ferric oxide yellow oxide (E172), dye iron black oxide (E172)).

Film-coated tablets, 20 mg:

Opadry II 33G27237 (tan) (hypromellose (E464), titanium dioxide (E171), lactose monohydrate, macrogol-3000, triacetin, dye iron oxide red (E172), ferric iron oxide yellow (E172)).

Tablets coated with a coating, 40 mg:

Opadry II 33G24896 (pink) (hypromellose (E464), titanium dioxide (E171), lactose monohydrate, macrogol-3000, triacetin, dye iron oxide red (E172)).

Description:

Tablets, film-coated, 10mg:

from light pink to slightly yellowish brown oval tablets covered with a film sheath, with an engraving "10" on one side.
Film-coated tablets, 20 mg:from yellowish brown to light brown oval tablets, covered with a film shell, with an engraving "20" on one side.
Tablets coated with a coating, 40 mg:from pink to pink with a slightly brown tinge oval tablets covered with a film shell, with an engraving "40" on one side.
At the break of the tablet - the core of white color.

Pharmacotherapeutic group:Hypolipidaemic agent - 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 a fermentation product Aspergillus terreus, is an inactive lactone in the body undergoes 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 catalyzing the initial reaction of formation of mevalonate from HMG-CoA. Since the conversion of HMG-CoA to mevalonate is 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 easily metabolized to acetyl-CoA, which is involved in many synthesis processes in the body. Simvastatin reduces the plasma levels of triglycerides (TG), low-density lipoproteins (LDL), very low density lipoproteins (VLDL), and total cholesterol (in cases of heterozygous familial and non-family forms of hypercholesterolemia, with mixed hyperlipidemia, when elevated cholesterol is a risk factor) .Increases the high-density lipoprotein (HDL) content and reduces the ratio of LDL / HDL and total cholesterol / HDL. The onset of the effect is 2 weeks after the start of the treatment, the maximum therapeutic effect is achieved in 4-6 weeks. The effect persists with the continuation of treatment, with the cessation of therapy the cholesterol content gradually returns to the initial value (before the start of treatment).

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 about 95%.

Metabolized in the liver, has the effect of "first passage" through the liver (hydrolyses to form an active derivative: 0-hydroxy acid, found other active, as well as inactive metabolites). The half-life of active metabolites is 1.9 hours.

It is excreted primarily through the intestine (60%) in the form of metabolites. About 10-15% is excreted by the kidneys in an inactive form.

Indications:

Hypercholesterolemia:

- homozygous hereditary hypercholesterolemia;

- primary hypercholesterolemia (type IIa and IIb according to Fredrickson) with ineffectiveness of diet therapy with low cholesterol and other non-drug measures (physical activity and weight loss) in patients with an increased risk of coronary atherosclerosis;

- combined hypercholesterolemia, hypertriglyceridemia, hyperlipoproteinemia, which can not be corrected by special diet and exercise.

Cardiac ischemia:

- to slow the progression of the disease;

- to reduce the risk of coronary death and prevent myocardial infarction;

- to reduce the likelihood of undergoing an operation to restore coronary blood flow (aortocoronary bypass and percutaneous transluminal coronary angioplasty);

- to slow the progression of coronary atherosclerosis;

Cerebrovascular disease:

- to reduce the risk of stroke and transient cerebral circulation.

Contraindications:

- Hypersensitivity to simvastatin or to other components of the drug (including hereditary lactose intolerance),as well as to other drugs of the statin series (inhibitors of HMG-CoA reductase) in the anamnesis;

- Deficiency of lactase, glucose-galactose malabsorption;

- liver disease in the active phase, persistent increase in the activity of "liver" enzymes of unclear etiology;

- diseases of skeletal muscles (myopathy);

- age to 18 years (efficacy and safety not established).

Carefully:

Carefully prescribe patients who abuse alcohol, patients after transplantation of the organs undergoing therapy immunosuppressants (due to an increased risk of rhabdomyolysis and renal failure); at conditions that can lead to the development of severe renal failure, such as arterial hypotension, acute infectious diseases of severe course, severe metabolic and endocrine disorders, water-electrolyte balance disorders, surgical interventions (including dental), or trauma; patients with decreased or increased tone of skeletal muscles of unknown etiology; epilepsy.

Pregnancy and lactation:

Simvastatin is contraindicated during pregnancy.There are several reports of the development of anomalies in newborns whose mothers were taking simvastatin.

Women of childbearing age who receive simvastatin, must to avoid conception. If in the course of treatment the pregnancy nevertheless has come, simvastatin should be canceled.

Data on the isolation of simvastatin with breast milk are absent. If it is necessary to prescribe the drug during the period of breastfeeding, it should be borne in mind that many drugs are excreted in breast milk and there is a threat of development of severe reactions, so breast-feeding during taking the drug is not recommended.

Dosing and Administration:

Before the start of treatment with Simvastatin-Teva, the patient should be prescribed a standard hypocholesterol diet, which should be observed throughout the course of treatment.

The drug Simvastatin-Teva should be taken orally 1 time per day in the evening, regardless of food intake, with plenty of water.

Hypercholesterolemia: usually the initial dose is 10 mg 1 time / day in the evening.

When mild to moderate hypercholesterolemia the initial dose is 5 mg / day.

When choosing a dose, increase the dose should be made, observing the 4-week intervals. In most patients, the optimal effect is achieved when taking the drug at doses up to 20 mg per day. The maximum daily dose is 80 mg.

In patients with homozygous hereditary hypercholesterolemia the recommended daily dose of Simvastatin-Teva is 40 mg once a day in the evening or 80 mg / day, divided into 3 doses (20 mg in the morning, 20 mg in the afternoon and 40 mg in the evening).

In the treatment of patients from ischemic heart disease (CHD) or a high risk of CHD First appoint a dose of 20 mg 1 time / day, in the evening. If necessary, the dose is increased gradually with an interval of 4 weeks to 40 mg. 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.

Have elderly patients and patients with mild or moderate degree renal failure no change in dosage is required.

In patients with chronic renal failure (creatinine clearance less than 30 ml / min) or receiving ciclosporin, danazol, gemfibrozil or other fibrates (except fenofibrate), nicotinic acid in doses that lower the concentration of lipids in the blood plasma,(more than 1 g / day) in combination with simvastatin, the maximum recommended dose of Simvastatin-Teva should not exceed 10 mg per day.

For patients receiving amiodarone or verapamil Simvastatin-Teva, the daily dose of Simvastatin-Teva should not exceed 20 mg.

Side effects:

The incidence of adverse reactions described below was determined according to the WHO classification:

Rarely: (> 0.01%, <0.1%).

From the digestive system: rarely - abdominal pain, constipation, flatulence, nausea, diarrhea, vomiting, acute pancreatitis, hepatitis, increased activity of "liver" enzymes, alkaline phosphatase and creatine phosphokinase (CKF).

From the central nervous system and sensory organs: rarely - asthenia, headache, dizziness, insomnia, muscle cramps, paresthesia, peripheral neuropathy, blurred vision, impaired taste sensations.

Allergic and immunopathological reactions: rarely - skin rash, itching, urticaria, angioedema, lupus-like syndrome, rheumatic polymyalgia, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis, arthralgia, photosensitivity, fever, skin hyperemia, blood flushes to the skin of the face, dyspnea.

From the musculoskeletal system: rarely - myopathy, myalgia, myasthenia gravis, muscle cramps, weakness, rhabdomyolysis.

Other: anemia, palpitations, acute renal failure (due to rhabdomyolysis), decreased potency.

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 activity of CKK in the blood serum.

With the development of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), stop taking the medication immediately and administer the patient diuretic and sodium hydrogen carbonate (intravenous infusion). With oliguria and anuria hemodialysis is indicated.

When developing hyperkalemia against rhabdomyolysis, intravenous calcium chloride or calcium gluconate should be used, glucose infusion with insulin, potassium ion exchangers or, in severe cases, hemodialysis.

Interaction:

Cytostatics, antifungal agents (ketoconazole, itraconazole), fibrates, high doses of nicotinic acid, immunosuppressants, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone increase the risk of myopathy.

Cyclosporine or danazol: The risk of myopathy / rhabdomyolysis increases with the simultaneous administration of cyclosporine or danazol with high doses of simvastatin.

Other hypolipidemic 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 CYP3A4, but capable of causing myopathy in conditions monotherapy. Gemfibrozil and other fibrates (except fenofibrate) have this effect, and a nicotinic acid in a dose> 1 g per day.

Amiodarone and verapamil: The risk of myopathy increases with the joint administration of amiodarone or verapamil with high doses of simvastatin.

Diltiazem: The risk of myopathy is slightly increased in patients receiving diltiazem simultaneously with simvastatinom in a dose of 80 mg.

Simvastatin potentiates the action indirect anticoagulants (for example, fenprokumone, warfarin) and increases the risk of bleeding, which requires monitoring the coagulability of the blood before the treatment, and often enough in the initial period of therapy. Once a stable prothrombin time or international normalized ratio (MNO) is reached, further monitoring should be performed at intervals recommended for patients receiving indirect anticoagulant therapy. When changing the dose or stopping the intake of simvastatin, it should also be monitored prothrombin time or INR in 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.

Increases concentration digoxin in the blood plasma.

Kolestyramine and colestipol reduce the bioavailability (the use of simvastatin is possible 4 hours after the administration of these drugs, with an additive effect noted).

Grapefruit juice contains one or more components that inhibit the isoenzyme CYP3A4 and can increase the concentration of blood in the blood plasma metabolized with the participation of isoenzyme CYP3A4. The 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 of HMG-CoA reductase. In this regard, it is necessary to avoid the consumption of grapefruit juice in large quantities.

Special instructions:

At the beginning of therapy with the drug Simvastatin-Teva, a transient increase in the activity of "hepatic" enzymes is possible.

Before the start of therapy and further it is recommended to carry out regular liver function tests (to 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, a determination of liver function should be performed. When the dose is raised to 80 mg, this test should be carried out every 3 months. With a persistent increase in the activity of transaminases (more than 3 times compared with the baseline), the drug should be discontinued.

Simvastatin-Teva, like other inhibitors of HMG-CoA reductase,should not be used at an increased risk of rhabdomyolysis and renal failure (on the background of severe acute infection, hypotension, planned major surgery, trauma, severe metabolic disorders). 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 occurs, the drug should be canceled, and the woman is warned about possible danger to the fetus.

The use of the drug Simvastatin-Teva is not recommended in women of childbearing age who do not use reliable contraceptives.

In patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) withincreasing the concentration of cholesterol should be first conducted treatment of the underlying disease.

Preparation Simvastatin-Teva with caution prescribed to 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, so you should avoid their simultaneous administration.

The drug Simvastatin-Teva is not indicated in cases where there is hypertriglyceridemia I, IV and V type.

Treatment with the drug Simvastatin-Teva can cause myopathy, leading to rhabdomyolysis and kidney failure. The risk of this pathology increases in patients receiving simultaneously Simvastatin-Teva one or more of following medicines: fibrates (gemfibrozil, fenofibrate), ciclosporin, nefazadone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of "azoles" (ketoconazole, intraconazole) and HIV protease inhibitors (ritonavir).The risk of developing myopathy is also increased in patients with severe renal failure.

All patients starting therapy with Simvastatin-Teva, as well as patients who need to increase the dose of the drug, should be warned about the possibility of myopathy and the need to immediately seek medical attention in the event of unexplained pain, muscle soreness, lethargy or muscle weakness, especially if this is accompanied by a 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 the drug Simvastatin-Teva, an increase in serum CKF is possible, which should be taken into account in the differential diagnosis of chest pain. The criterion for discontinuation of the drug is an increase in the activity of CK in the blood serum more than 10 times as compared with the upper limit of the norm. In patients with myalgia, myasthenia gravis and / or a marked increase in the activity of CKK, treatment with the drug is stopped.

The drug is effective both in the form of monotherapy, and in combination with sequestrants of bile acids.

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 failure receive treatment 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 Simvastatin-Teva on the ability to drive and work with machinery has not been reported.

Form release / dosage:

Tablets, film-coated, 10 mg, 20 mg, 40 mg.

Packaging:

For 10 tablets in a blister of PVC and aluminum foil.

For 3 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

List B.

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 N015543 / 01

Date of registration:22.12.2009

Expiration Date:Unlimited

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Representation: & nbspTeva Teva Israel

Information update date: & nbsp28.12.2016

Illustrated instructions

Instructions

Simvastatin-Teva (Simvastatin-Teva)