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

Excipients: lactose (milk sugar), potato starch, microcrystalline cellulose, ascorbic acid, citric acid, copovidone (Kollidon VA-64), magnesium stearate, silicon dioxide colloid (aerosil).

Film sheath: Opaprai II (series 85): polyvinyl alcohol partially hydrolyzed, macrogol-3350, talc, titanium dioxide E 171, iron dye oxide black E 172, iron dye oxide yellow E 172, aluminum dye based on dye red \ Charming E 129 .

Description:the tablets covered with a film cover of pink color, round, biconcave. On the fracture is white or almost 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 the fermentation product of 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. It causes a decrease in plasma concentrations 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, mixed hyperlipidemia,when increased cholesterol concentration is a risk factor). Increases the concentration of high density lipoproteins (LPVG1) and reduces the ratio of LDL / HDL and total cholesterol / LPVII. 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 effect persists with the continuation of treatment, with the cessation of therapy, the concentration of cholesterol gradually returns to the initial value.

Pharmacokinetics:

Suction: after oral administration simvastatin is absorbed from the gastrointestinal tract (GIT) - about 61-85 % and enters the systemic circulation. The maximum therapeutic concentration in the blood plasma is achieved in 1.3 - 2.4 hours and decreases by 90% after 12 hours. Simultaneous food intake does not affect the absorption of simvastatin. Distribution: the binding to plasma proteins is about 98%.

Metabolism: simvastatin is subjected to the effect of "first passage" through the liver (mainly hydrolysed to its active form beta hydroxy acid). In the metabolism of the drug, isozymes participate CYP3A4, CYP3A5 and CYP3A7.

The concentration of the active metabolite of simvastatin in the systemic circulation is 5% of the dose.

Excretion: the half-life of active metabolites is 1.9 hours. It is excreted mainly through the intestine (about 60%) in the form of metabolites. About 10-15% is excreted by the kidneys in an inactive form.

Indications:

primary hypercholesterolemia (type Pa and PN according to Frederickson) 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;

homozygous hereditary hypercholesterolemia (as an adjunct to hypolipidemic therapy);

ischemic heart disease (secondary prevention): the drug is indicated to patients in order to reduce the overall mortality; with the aim of reducing the risk of coronary mortality and preventing myocardial infarction; with the aim of reducing the risk of stroke and transient cerebral circulatory disorders; with the purpose of slowing the progression of coronary atherosclerosis.

Contraindications:

Contraindications

- increased sensitivity to the components included in the preparation, including, to Simvastatin and other drugs of the statistic series (inhibitors of HMG-CoA reductase);

- hepatic insufficiency and liver diseases in the active phase, increased activity of "liver" transaminases of unknown origin:

- porphyria;

diseases of skeletal muscles (myopathy);

- pregnancy and lactation;

- age under 18 years (safety and efficacy not established);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

- concomitant use with strong inhibitors of the isoenzyme CYP3A4 (itraconazole, post-opazole, voriconazole, HIV protease inhibitors, bocetrevir, telaprsvir, erythromycin, clarithromycin, telithromycin, nefazodone and preparations containing co-bicystate);

- concomitant treatment with gemfibrozil, cyclosporin or danazol.

Carefully:Be wary appoint patients with alcohol abuse, liver disease history, patients after organ transplantation, who undergo immunosuppressant therapy (due to an increased risk of rhabdomyolysis and renal insufficiency); at states,which can lead to the development of severe renal failure, such as arterial hypotension, acute infectious diseases of severe course, severe metabolic and endocrine disorders, disturbances of water-electrolyte balance, surgical interventions (including dental), or trauma; patients with decreased or increased tone of skeletal muscles of unknown etiology; epilepsy, uncontrolled convulsions; with simultaneous reception of dronsdarone.

Pregnancy and lactation:

Simvastatin is contraindicated in pregnancy. Women of childbearing age who receive drug, should avoid conception. If during pregnancy the pregnancy has occurred, it is necessary to cancel the intake of Simvastatin, and the woman should be warned about the possible danger to the fetus. Data on the isolation of simvastatin in breast milk are absent.

If it is necessary to administer the drug Simvastatin During lactation breastfeeding should be discontinued.

Dosing and Administration:

Dosing and Administration

Before the start of Simvastatin treatment, the patient should be prescribed a standard hypocholesterin diet, which should be observed throughout the course of treatment.Simvastagin is taken orally 1 time per day in the evening, with plenty of water. The time of taking the drug should not be associated with taking a baby. The recommended initial dose for patients with severe 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 a dose of 20 mg per day.

With homozygous hereditary hypercholesterolemia, the recommended daily dose of simvastatin 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 ischemic heart disease, an initial dose of 20 mg per day in the evening; if necessary, the dose is gradually increased every 4 weeks to 40 mg.

In elderly patients and in patients with mild or moderate degree of renal failure, dose changes are not required.

In patients with chronic renal insufficiency (creatinine clearance less than 30 ml / min) or receiving nicotinic acid in lipid-lowering doses (> 1 g / day) in combination with Simvastatin, the maximum recommended dose of simvastatin should not exceed 10 mg per day.

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

For patients receiving dronedaron Simvastatin simultaneously, the daily dose of Simvastatinium should not exceed 10 mg.

Side effects:

If it is necessary to administer the drug Simvastatin During lactation breastfeeding should be discontinued.

Overdose:

In none of several known cases of overdose (the maximum dose taken 450 mg) there were no specific symptoms.

Treatment: cause vomiting, take Activated carbon, symptomatic therapy. It is necessary to monitor the liver and kidney function, the activity of CKK in the blood serum. There is no specific antidote, hemodialysis is ineffective.

Several cases of overdose were reported, the maximum dose taken was 3.6 g. None of the patients had an overdose effect.

For the treatment of overdose, general measures are taken, including maintenance and symptomatic therapy.

Interaction:

Contraindicated combinations of medicines

Contraindicated concomitant therapy with the following drugs: Strong 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 administration of simvastatinium affects the concentration in the blood plasma of drugs metabolized by the CYP3A4 isoenzyme. Strong inhibitors of the CYP3A4 isoenzyme increase the risk of myopathy by reducing the rate of withdrawal of simvastatin. Simultaneous, less severe inhibitors of the isoenzyme CYP3A4 (eg, itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, bocetrevira, telaprevir, nefazodone and preparations containing the co-bicarbonate) and simvastatia are contraindicated.

- Gemfibrozil. ciclosporin or danazol (concomitant use is contraindicated because of the risk of myopathy / rhabdomyolysis).

Interaction with other drugs

Simvastatin enhances the effect of oral anticoagulants (for example, fenprocumone, warfarin) and increases the risk of bleeding, which requires the need to monitor the coagulability of the blood before the treatment, and often enough in the initial period of therapy. Once achieved stable performance irotrom- bnnovogo time or international normalized ratio (INR), its further monitoring should be carried out at intervals recommended for patients receiving 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. It increases the risk of myopathy administration of other lipid-lowering agents (which are not strong inhibitors of isoenzyme CYP3A4, but can cause myopathy monotherapy conditions), such as fibrates (except fenofibrate), and nicotinic acid at a dose of> 1 g per day.

The risk of myopathy increases with the combined use of amiodarone or verapamnl with high doses of simvastatin.

The risk of developing myopathy and rhabdomyolysis increases with the simultaneous use of simvastatin with dronzdarone.

The risk of developing myopathy increases with the simultaneous use of simvastatin with fusidic acid or colchicine.

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

Simvastatin increases the concentration of di-toxin in the blood plasma.

Kolestyramin and colestipol reduce 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 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 administration of simvastatin significantly increases the inhibitory activity against HMG-CoA reductase in blood plasma.In this regard, you must avoid the use of grapefruit juice in large quantities.

Special instructions:

special instructions

Simvastatii is effective both in the form of monotherapy, and in combination with bile acid sequestrants.

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

If the current dose is skipped, the drug should be taken as soon as possible. If it's time for the next dose, do not double the dose.

Duration of the drug is determined individually by the attending physician. Before starting therapy, continue to conduct regular liver function tests (monitor the activity of "liver" transaminases 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). Patients receiving Simvastaty in a daily dose of 80 mg, liver function is monitored every 3 months. In those cases when the activity of "hepatic" transaminases increases (exceeding the upper limit of the norm by 3 times), therapy is canceled.

In patients with myalgia, myasthenia gravis and / or with a marked increase in the activity of CKK, treatment with the drug is stopped.Simvastatii, like other inhibitors of HMG-CoA reductase, should not be used at an increased risk of rhabdomyolysis and renal insufficiency (due to severe acute infection, arterial hypertension, large surgical surgery, trauma, severe metabolic disorders). The abolition of hypolinidemic drugs during pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.

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. Simvastatin is not indicated in cases where there is ginertriglitseridemiya I. IV and V type. All patients starting therapy with the drug Simvastatin, 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 myasthenia gravis, especially if accompanied by a malaise or fever.The drug should be discontinued immediately if myopathy is diagnosed or suspected. Concomitant therapy with strong inhibitors of the CYP3A4 isoenzyme at therapeutic doses (for example, itracoazole, bipolysis, iozaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and preparations containing cobicisgate) is contraindicated. If you avoid short-term treatment with strong inhibitors of isofermene CYP3A4 can not. drug therapy Simvastatin should be interrupted for the period of their application. Moderate inhibitors of the isoenzyme CYP3A4 (eg, dronedaron) may increase the risk of myopathy, especially at high doses of simvastatin. When Simvastatin and moderate inhibitors of CYP3A4 isoenzymes are used concomitantly, a reduction in the dose of simvastatin may be required.

In order to diagnose the development of myopathy, it is recommended to regularly measure the value of CK.

When treating with the drug Simvasmagin, an increase in the serum CKF content is possible, which should be taken into account in differential diagnosis of chest pain.The criterion for the discontinuation of the drug is an increase in serum levels of CK in more than 10 times the upper limit of the norm. In patients with myalgia, myasthenia gravis, and / or a marked increase in the activity of CPK, the drug intake is discontinued on the background of treatment. Patients with severe renal failure receive treatment under the control of kidney function.

Therapy with simvastatin does not cause changes in prothrombin time and the risk of bleeding in patients taking anticoagulants.

Influence on the ability to drive vehicles and engage in other activities that require concentration of attention and speed of psychomotor reactions. The adverse effect of the drug on the ability to drive vehicles and engage in other activities that require concentration and speed of psychomotor reactions were not reported. However, given that the drug can cause dizziness, blurred vision, you should be careful when implementing these activities.

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

Influence on the ability to drive vehicles and engage in other activities that require concentration of attention and speed of psychomotor reactions. The adverse effect of the drug on the ability to drive vehicles and engage in other activities that require concentration and speed of psychomotor reactions were not reported. However, given that the drug can cause dizziness, blurred vision, you should be careful when implementing these activities.

Form release / dosage:

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

By 10 tablets into a contour mesh box made of polyvinyl chloride film and aluminum foil printed lacquered.

3 contour packagings along with the toolksieth nabout primyenMr.andyu pomconsciencein pachku from cardboard.

Packaging:

By 10 tablets into a contour mesh box made of polyvinyl chloride film and aluminum foil printed lacquered.

3 contour packagings along with the toolksieth nabout primyenMr.andyu pomconsciencein pachku from cardboard.

Storage conditions:

In a place protected from light and moisture, at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use at the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001180

Date of registration:27.08.2010

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Representation: & nbspVALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Information update date: & nbsp30.07.2015

Illustrated instructions

Instructions

Simvastatin (Simvastatin)