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

Excipients: lactose monohydrate, butylhydroxyanisole, ascorbic acid, citric acid monohydrate, microcrystalline cellulose PH 101, pregelatinized starch, magnesium stearate

Shell composition: Opadrai II 33G24737 (hypromellose, lactose monohydrate, titanium

dioxide, macrogol, glycerol triacetate, iron dye oxide red, aluminum lacquer based on indigo carmine dye, iron oxide dye black).

Tablets of 20 mg.

Active substance: simvastatin 20 mg

Excipients: lactose monohydrate, butylhydroxyanisole, ascorbic acid, citric acid monohydrate, microcrystalline cellulose PH 101, pregelatinized starch, magnesium stearate

Shell composition: Opadry II 39G22514 (Hypromellose, titanium dioxide, lactose monohydrate, Macrogol, triacetin, iron oxide colorant yellow, iron oxide red dye, iron oxide black dye).

Description:

Tablets 10 mg - round biconvex tablets, covered with a film shell of pink color. On the cut, two layers are visible, the core is uniformly white, with a thin, pink coating on the edge of the core.

Tablets 20 mg - round biconvex tablets, covered with a film coating of yellow color. On the cut, two layers are visible, the core is uniformly white, with a thin yellow coating on the edge of the nucleus.

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 is exposed to form 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.

It causes a decrease in 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 high cholesterol is a risk factor) .

Increases of high density lipoprotein (HDL) 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 after 4-6 weeks.The effect persists with the continuation of treatment, with the cessation of therapy, the cholesterol content gradually returns to the baseline level.

Pharmacokinetics:

Absorption of simvastatin is 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 a "first pass" through the liver (hydrolyses to form an active derivative: beta-hydroxy acid, other active as well as 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 Nb) 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 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

cardiovascular disorders (stroke or transient ischemic attacks),

slowing the progression of coronary artery atherosclerosis, reducing the risk of revascularization procedures.

Contraindications:

increased sensitivity to simvastatin or to other components of the drug (including hereditary lactose intolerance), as well as to other statin drugs (inhibitors of HMG-CoA reductase) in the anamnesis;
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 organ transplantation, who undergo immunosuppressant therapy (due to an increased risk of rhabdomyolysis and kidney failure); at conditions that can lead to the development of severe renal failure, such as arterial hypotension,acute infectious diseases of severe course, expressed metabolic and endocrine disorders, violations of water and electrolyte balance, surgical interventions (including dental), or trauma; patients with decreased or increased tone of skeletal muscles of unknown etiology; epilepsy, liver disease in the anamnesis.

Pregnancy and lactation:

Simvastol® is contraindicated in pregnancy. There are several reports of the development 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, Simvastol® 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 prescribe Simvastol® 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 the treatment with Simvastol®, the patient should be prescribed a standard hypocholesterin diet, which should be observed throughout the course of treatment.

Simvastol® should be taken 1 time per day in the evening, with plenty of water.

To ensure the following dosing regimen, it is recommended to use the preparation of Simvastol® 10 mg and 20 mg.

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

Recommended dose for treatment hypercholesterolemia varies from 10 to 80 mg once a 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 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 (CHD) or a high risk of CHD development, effective doses of Simvastol® 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 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.

Have elderly patients and in patients with mild or moderate degree renal insufficiency 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), a 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 Simvastol® daily dose of Simvastol® should not exceed 20 mg.

Side effects:

Digestive system: abdominal pain, constipation, flatulence, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increased activity of "liver" enzymes, alkaline phosphokinase and creatine phosphokinase (CKF).

Nervous system and sensory organs: asthenic syndrome, headache, dizziness, insomnia, muscle cramps, paresthesia, peripheral neuropathy, blurred vision, impaired taste sensations.

Allergic and immunopathological reactions: angioedema,

Rheumatic polymyalgia, vasculitis, thrombocytopenia, increased ESR,

fever, arthritis, urticaria, photosensitivity, skin hyperemia, hot flashes, dyspnea, lupus-like syndrome, eosinophilia.

Dermatological reactions: rarely skin rash, itching, alopecia, dermatomyositis.

From the musculoskeletal system: Myopathy, myalgia, muscle cramps, weakness; rarely rhabdomyolysis.

Other: Anemia, palpitation, 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 level of CK in the blood serum.

With the development of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), the drug should be stopped immediately and the diuretic and sodium bicarbonate (intravenous infusion) administered to the patient. If necessary, hemodialysis is indicated.

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

Interaction:

Cytotoxic agents, antifungal agents (ketocobalase, 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 myopathy increases with the co-administration of other lipid-lowering drugs that are not potent inhibitors CYP3A4, but capable of causing myopathy under conditions of monotherapy. Such as gemfibrozil and other fibrates (except fenofibrate), as well as niacin (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 oral anticoagulants (eg fenprokumone, warfarin) and increases the risk of bleeding, which requires the need to monitor the coagulability of the blood before treatment, and often enough in the initial period of therapy. Once a stable prothrombin time indicator or International Normalized Ratio (MNO) is reached, its further control 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.

Increases the level 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 ingredients that inhibit CYP3A4 and can increase the concentration in the blood plasma of metabolic agents CYP3A4. The increase in activity of GIG-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-CoA reductase in blood plasma. In this regard, it is necessary to avoid the consumption of grapefruit juice in large quantities.

Special instructions:

At the beginning of Simvastol® therapy, a transient increase in the level of "liver" enzymes is possible.

Before the beginning of therapy, and further regularly carry out a study of liver function (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 once every six months), as well as with increasing doses, a test should be performed to determine the function of the liver. When the dose is raised to 80 mg, a test should be performed every 3 months. With a persistent increase in transaminase activity (3-fold compared with baseline), Simvastol® should be discontinued.

Simvastol®, like other HMG-CoA reductase inhibitors, should not be used at an increased risk of rhabdomyolysis and renal insufficiency (against severe acute infection, arterial hypotension, planned large 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 simvastol® is not recommended for 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), when the level of cholesterol is increased, the underlying disease should first be treated. Precautions are prescribed for persons 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 Simvastol®, therefore, simultaneous reception should be avoided.

Simvastol® is not indicated in cases where there is hypertriglyceridemia I, IV and V types.

Treatment with simvastol® can cause myopathy, leading to rhabdomyolysis and kidney failure. The risk of this pathology increases in patients,receiving simultaneously with Simvastol® one or more of the following medicines: fibrates (gemfibrozil, fenofibrate), ciclosporin, nefazodone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of "azoles" (ketoconazole, itraconazole) and HIV protease inhibitors (ritonavir). The risk of developing myopathy is also increased in patients with severe renal failure. All patients starting Symvastol® 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 to immediately seek medical attention in the event of unexplained pain, muscle soreness, lethargy or muscle weakness, especially if 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 that CK values be measured regularly.

When treating the drug, it is possible to increase the content of serum CK, 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 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 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 insufficiency ^ treatment are under control 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 effects of simvastatin on the ability to drive and work with machinery have not been reported.

Form release / dosage:

Tablets, film-coated 10 and 20 mg.

Packaging:

For 14 tablets coated with a film sheath in a blister of A1 / PVC

For 1 or 2 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

List B.

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N015147 / 01

Date of registration:24/04/2008

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER ROMANIA, S.A. Romania

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp01.08.2015

Illustrated instructions

Instructions

Simvastol® (Simvastol®)