SIMVALIMIT - instructions for use, dose, side effects, contraindications

mcellulose, 85.82 mg; methylcellulose - 2.50 mg; magnesium stearate - 2.80 mg; butylhydroxyanisole 0.04 mg; ascorbic acid 5.00 mg; citric acid, monohydrate - 3.00 mg;

shell, tablets 10 mg:

33G 28707 Opaprayi white (hypromellose-40,000%, lactose monohydrate - 24,000%, macrogol 3000 - 22,000%, titanium dioxide (E 171) - 8,000%, triacetin - 6,000%) - 5.60 mg, carnauba wax;

tablets 20 mg:

85F 24678 Opadrai pink (polyvinyl alcohol, partially hydrolyzed, - 40,000%; titanium dioxide (E 171) - 24.930%; macrogol 3000 - 20,200%; talcum - 14,800%; iron oxide black (E 172) - 0.020%; iron oxide yellow (E 172) - 0.010%; carmozine (azorubin) (E 122) 0.040%) 11.20 mg, carnauba wax.

Description:

Tablets 10 mg: round biconvex tablets covered with a white sheath, on the fracture white.

Tablets of 20 mg: round biconvex tablets, coated with a light pink color, on the fracture white.

Pharmacotherapeutic group:lipid-lowering 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 that catalyzes the initial reaction of mevalonate formation 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 causes a decrease in 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 ) by inhibiting the synthesis of cholesterol in the liver and increasing the number of LDL receptors on the surface of cells, which leads to increased capture and catabolism of LDL.

Increases the high-density lipoprotein (HDL) content and reduces the ratio of LDL / HDL and total cholesterol / HDL. Does not have a mutagenic effect.

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 is high, bioavailability is less than 5%. 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%.

It enters the body in an inactive form. Hydrolyses in tissues into its active form - beta-hydroxy acid and inactive metabolites. Metabolized in the liver, has the effect of "first pass" through the liver. In the metabolism of the drug participate isozymes CYP3A4, CYP3A5 and CYP3A7. 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

Primary hypercholesterolemia (heterozygous familial and non-family, types of Pas, Pb and mixed according to Fredrickson classification) - with ineffectiveness of diet with low cholesterol and other non-drug measures (physical activity and weight loss) in patients with an increased risk of coronary atherosclerosis,
combined hypercholesterolemia and hypertriglyceridemia, hyperlipoproteinemia, which can not be corrected by a special diet and exercise;

Ischemic heart disease

secondary prophylaxis to reduce the overall risk of death, myocardial infarction (to slow the progression of coronary atherosclerosis), stroke and transient cardiovascular disorders, 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 GMC-CoA reductase) in the anamnesis,
liver disease in the active phase, or persistent increase in the activity of "hepatic" transaminases of unclear etiology,
simultaneous administration of cytochrome P450 inhibitors of ZA4 (isoenzyme CYP3A4) (eg, itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone),
diseases of skeletal muscles (myopathy),
pregnancy and lactation,
age to 18 years (efficacy and safety of use not studied),
deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome.

Carefully:

alcoholism, liver disease in history, severe

disturbances of water-electrolyte balance, expressed endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), myopathy, uncontrolled epilepsy, extensive surgical interventions, trauma; simultaneous administration with fibrates, cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), amiodarone, verapamil, diltiazem, grapefruit juice; marked renal failure (creatinine clearance less than 30 ml / min).

Pregnancy and lactation:

Simvastatin may adversely affect the fetus and is contraindicated in pregnant women. There are several reports of the development of anomalies in newborns whose mothers were taken by SIMVALIMIT®.

Women of reproductive age who take SIMVALIMIT® should avoid conception. The use of the drug SIMVALIMIT® is not recommended in women of childbearing age who do not use reliable methods of contraception. If during pregnancy the pregnancy does occur, SIMVALIMIT® should be canceled, and a woman should be warned about the possible danger to the fetus.

Data on the isolation of simvastatin with breast milk are absent.If you need the use of the drug SIMVALIMIT® during 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 while taking the drug SIMVALIMIT® should be discontinued.

Dosing and Administration:

Before the start of treatment with the drug SIMVALIMIT the patient should be prescribed a standard hypocholesterol diet, which should be observed throughout the course of treatment. SIMVALIMIT® should be taken 1 time per day in the evening, with plenty of water.

The time of taking the drug should not be associated with eating.

Duration of the drug is determined individually by the attending physician.

Hypercholesterolemia

The recommended dose of the drug SIMVALIMIT® for treatment hypercholesterolemia varies from 5 to 80 mg once a day in the evening. The recommended initial dose of the drug is usually 10 mg for patients with hypercholesterolemia. 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 the drug SIMVALIMIT is 40 mg (2 tablets of 20 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). These patients are recommended to use SIMVALIMIT® in combination with other lipid-lowering therapy (for example, LDL-apheresis).

Cardiac ischemia

In the treatment of patients with ischemic heart disease (CHD) or a high risk of developing coronary artery disease, with or without hyperlipidemia, effective doses of the drug SIMVALIMIT are 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 done at intervals of 4 weeks, if necessary, the dose can be increased to 40 mg per day (2 tablets of 20 mg of the drug SIMVALIMIT®). 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.

Concomitant therapy

In patients receiving cyclosporine, danazol, gemfibrozil, other fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day), the recommended maximum daily dose of the drug SIMVALIMIT® should not exceed 10 mg. Further increase in dose in such situations is not recommended.

For patients who simultaneously take amiodarone or verapamil, the daily dose of the drug SIMVALIMIT® should not exceed 20 mg.

For patients who simultaneously take diltiazem, the daily dose of the drug SIMVALIMIT® should not exceed 40 mg.

In elderly patients and in patients with mild or moderate renal insufficiency, dose adjustment is not required.

In patients with severe renal failure (creatinine clearance less than 30 ml / min), the recommended dose of the SIMVALIMIT® preparation should not exceed 10 mg per day. If it is necessary to increase the dose, careful monitoring of such patients is carried out.

Side effects:

Classification of the incidence of side effects is presented in accordance with the classification of the World Health Organization (WHO).

From the digestive system

Constipation, abdominal pain, flatulence, dyspepsia, nausea, vomiting, diarrhea, pancreatitis, hepatitis, jaundice, increased activity of "liver" transaminases, alkaline phosphatase and creatine phosphokinase (CK); rarely acute pancreatitis.

From the central nervous system and sense organs

Asthenia, headache, paresthesia, dizziness, peripheral neuropathy, insomnia, muscle cramps, blurred vision, a violation of taste.

From the side of the musculoskeletal system

Myopathy, rhabdomyolysis, myalgia, muscle cramps, weakness.

Allergic and immunopathological reactions

The developed syndrome of hypersensitivity (angioedema, lupus-like syndrome, rheumatic polymyalgia, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, increased erythrocyte sedimentation rate (ESR), arthritis, arthralgia, urticaria, photosensitivity, fever, blood flushes to the skin of the face, dyspnea) .

Dermatological reactions Skin rash, itching, alopecia.

Other

Anemia, palpitations, acute renal failure (due to rhabdomyolysis), decreased potency.

Overdose:

In none of the known few cases of overdose (the maximum dose taken is 450 mg), no specific symptoms were identified.

Treatment: symptomatic, it is necessary to carry out general measures: monitoring and maintaining vital functions, preventing further absorption of the drug (gastric lavage, taking activated charcoal or laxatives).It is necessary to monitor the liver and kidney function, the activity of CKK in the blood serum. There is no specific antidote.

With the development of myopathy with rhabdomyolysis (a rare but severe side effect), stop taking the medication immediately and inject the patient with a diuretic and sodium hydrogen carbonate (intravenous infusion).

Rhabdomyolysis can cause hyperkalemia, which can be eliminated by intravenous administration of calcium chloride or calcium gluconate, glucose infusion with insulin, the use of potassium ion-exchange sorbents or, in severe cases, by hemodialysis.

Interaction:

Pharmacodynamic interactions

Simultaneous use of simvastatin with fibrates, nicotinic acid (more than 1 g / day) increases the risk of myopathy, including rhabdomyolysis (with simultaneous use with fenofibrate, there is no evidence of an increased risk of myopathy compared with monotherapy with each drug alone). Simultaneous use with gemfibrozil can lead to an increase in the concentration of simvastatin in the serum.

Pharmacokinetic interactions

Inhibitor inhibitors CYP3A4 (itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors and nefazodone), involved in the metabolic conversion of simvastatin in the liver, increase the risk of myopathy and rhabdomyolysis during simvastatin therapy. Simultaneous use with these drugs is contraindicated. Caution should be given simultaneously with less potent inhibitors of the isoenzyme CYP3A4: cyclosporine, verapamil and

diltiazem.

The daily dose of the drug SIMVALIMIT® with simultaneous administration with cyclosporine should not exceed 10 mg.

The daily dose of the drug SIMVALIMIT® on the background of simultaneous reception of amiodarone or verapamil should not exceed 20 mg, and 40 mg - against the simultaneous reception of diltiazem, unless the expected benefit clearly exceeds the potential risk of myopathy and rhabdomyolysis.

Simvastatin in a dose of 20-40 mg / day in healthy volunteers and patients with hypercholesterolemia potentiates the effects of indirect anticoagulants - coumarin derivatives (for example, warfarin), in particular, an increase in prothrombin time and an international normalized relationship (INR). Therefore, in patients taking coumarin anticoagulants, prothrombin time and INR are necessary

determine before the start of simvastatin therapy, in the initial treatment period, with a change in the dose of simvastatin or withdrawal of the drug. When a stable prothrombin time and INR is reached, further monitoring should be performed at intervals recommended for patients receiving anticoagulant therapy. Therapy with simvastatin does not cause changes in prothrombin time and the risk of bleeding in patients who do not take anticoagulants. Kolestyramine and colestipol reduce bioavailability (the use of the drug SIMVALIMIT® is possible 4 hours after taking these drugs, with an additive effect noted).

Simvastatin increases the concentration of digoxin in the blood plasma.

Grapefruit juice contains one or more components that inhibit the isoenzyme CYP3A4 and can increase the concentration of blood in the blood plasma metabolized by isoenzyme CYP3A4. 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 the drug SIMVALIMIT® significantly increases the inhibitory activity against HMG-CoA reductase in blood plasma.In this regard, it is necessary to avoid the consumption of grapefruit juice in large quantities.

Special instructions:

In patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) with increasing cholesterol concentration, first therapy of the underlying disease should be performed.

Patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) are treated under the control of kidney function.

Treatment with the drug SIMVALIMIT®, like other inhibitors of GMC-CoA reductase, can cause myopathy, sometimes resulting in rhabdomyolysis with or without renal failure, due to myoglobinuria. The risk of myopathy increases with an increase in the dose of the drug SIMVALIMIT® and in patients with severe renal failure.

Among the predisposing factors for the development of myopathy, there are elderly (over 65 years), female, uncontrolled hypothyroidism and renal dysfunction.

In the treatment with the drug SIMVALIMIT®, an increase in the activity of CKF is possible, which should be taken into account in the differential diagnosis of chest pain and after performance of intensive physical exertion.

Before starting therapy with the drug SIMVALIMIT® or increasing its dose, patients should be informed of the risk of developing myopathy and the need to consult a doctor immediately if there is unexplained pain, tension or weakness in the muscles, especially if accompanied by malaise or fever. The initial activity of CKK before beginning therapy should be determined in the following situations:

in elderly patients,

when the kidney function is impaired, with decompensated hypothyroidism,

with a burdened family history of hereditary muscle diseases,

if there is a history of toxic effects on the muscles of lipid-lowering

means - inhibitors of HMG-CoA reductase (statins) or fibrates,

at abusing alcohol.

In the treatment with SIMVALIMIT®, it is necessary to evaluate the possible risk and the expected benefits of its use.If the CKK activity is initially significantly increased (more than 5 times the upper limit of the norm), the measurement should be repeated after 5-7 days to confirm the results. specified value of the activity of CKK preparation is not recommended.

Before and during the course of treatment, the patient should be on a hypocholesterol diet.

During treatment with the drug SIMVALIMIT® with the appearance of muscle pain, weakness or seizures, it is necessary to determine the activity of CK. The criterion for discontinuing the drug is an increase in the activity of CK in the blood serum more than 5 times the upper limit of the norm. If the symptoms from the muscles are severe and cause discomfort to the patient, even at a concentration of CK less than 5 times the upper limit of the norm, it may be necessary to stop treatment. If suspected of myopathy, therapy should be discontinued, regardless of the cause of myopathy.

If symptoms disappear and CPK activity returns to normal, re-administration of lipid-lowering drugs - inhibitors of EME-CoA reductase (statins) or an alternative drug of the same class in a minimally clinically effective dose and under careful medical supervision is possible.

Reception of the drug SIMVALIMIT® should be temporarily stopped a few days before major surgical interventions.

Measures to reduce the risk of myopathy caused by drug interactions

The risk of myopathy and rhabdomyolysis increases significantly with the simultaneous use of simvastatin and potent inhibitors of the isoenzyme CYP3A4 (eg, itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone) (see section "Interaction with other drugs"), which indicates a contraindication of their joint use.

The risk of myopathy and rhabdomyolysis also increases with the combined use of fibrates, cyclosporine and nicotinic acid in lipid-lowering doses (more than 1 g / day), as well as amiodarone and verapamil with high doses of the drug SIMVALIMIT® (above 20 mg / day). In patients who received diltiazem Simultaneously with preparation SIMVALIMIT in a dose of 80 mg, the risk of development of a myopathy increased.

Effects on the liver

Treatment with the drug SIMVALIMIT® can cause an increase in the activity of "liver" transaminases in the blood serum. This increase is usually insignificant and clinically insignificant. After the withdrawal of the drug SIMVALIMIT® activity of "liver" transaminases usually slowly decreases to the initial value. Nevertheless,before the beginning of treatment and further it is necessary to conduct a study of liver function (to monitor the activity of "liver" transaminases every 6 weeks for the first 3 months, then every 8 weeks for the remaining first year, and then 1 time in six months). If it is necessary to increase the dose to 80 mg, it is necessary to monitor the liver function before the dose increase, 3 months after the increase and then periodically (for example, every 6 months) during the first year of treatment with the drug SIMVALIMIT®. With a persistent increase in activity of aspartate aminotransferase (ACT) and / or alanine aminotransferase (ALT) in the serum 3 times higher than the upper limit of the norm, treatment with the drug SIMVALIMIT® should be discontinued.

With caution appoint patients who abuse alcohol and / or have a history of liver disease.

Effect on the ability to drive transp. cf. and fur:

On the adverse effect of the drug SIMVALIMIT® on the ability to drive vehicles and engage in other potentially hazardous activities requiring increased concentration and speed

psychomotor reactions were not reported.Nevertheless, it should be taken into account that when using the drug SIMVALIMIT®, isolated cases of dizziness and other side effects are noted that can affect these abilities.

Form release / dosage:

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

10 tablets per blister of a polyvinyl chloride film with polyvinylidene chloride coating and aluminum foil.

Three blisters together with instructions for use are placed in a pack of cardboard.

Packaging:

10 tablets per blister of a polyvinyl chloride film with polyvinylidene chloride coating and aluminum foil.

Three blisters together with instructions for use are placed in a pack of cardboard.

Storage conditions:

Store in a dry, dark 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.

Terms of leave from pharmacies:On prescription

Registration number:П N015509 / 01

Date of registration:28.04.2011

The owner of the registration certificate:GRINDEX, JSC GRINDEX, JSC Latvia

Manufacturer: & nbsp

Grindeks, JSC Latvia

Information update date: & nbsp28.04.2011

Illustrated instructions

Instructions

SIMVALIMIT® (Simvalimit)