SIMWASTOL

Active material: Simvastatin
When ATH: C10AA01
CCF: Lipid-lowering drugs
ICD-10 codes (testimony): E78.0, E78.2, G45, I21, I25.1, I61, I63
When CSF: 01.12.11.03
Manufacturer: GEDEON RICHTER ROMANIA S.A. (Romania)

Pharmaceutical form, composition and packaging

Pills, Film-coated Pink colour, round, lenticular; to cut two layers are visible: the nucleus uniformly white, with a thin pink coating at the edge of the nucleus.

Excipients: lactose monohydrate, ʙutilgidroksianizol, vitamin C, citric acid monohydrate, microcrystalline cellulose PH101, pre-gelatinized starch, magnesium stearate.

The composition of the shell: Opadry II 33G24737 (gipromelloza, lactose monohydrate, Titanium dioxide, macrogol, glycerol triacetate, iron oxide red dye, aluminium lacquer on the basis of the dye Indigo Carmine, dye iron oxide black).

14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pills, Film-coated yellow color, round, lenticular; to cut two layers are visible – the nucleus uniformly white with a thin yellow coating on the edge of the kernel.

Excipients: lactose monohydrate, ʙutilgidroksianizol, vitamin C, citric acid monohydrate, microcrystalline cellulose PH101, pre-gelatinized starch, magnesium stearate.

The composition of the shell: Opadry II 39G22514 (gipromelloza, Titanium dioxide, lactose monohydrate, macrogol, triacetine, iron oxide red dye, dye iron oxide yellow, dye iron oxide black).

14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pills, Film-coated Brown color, round, lenticular; to cut two layers are visible: the nucleus uniformly white, with a thin Brown coating on the edge of the kernel.

Excipients: lactose monohydrate, ʙutilgidroksianizol, vitamin C, citric acid monohydrate, microcrystalline cellulose PH101, pre-gelatinized starch, magnesium stearate.

The composition of the shell: Opadry II 33G26729 (gipromelloza, Titanium dioxide, lactose monohydrate, macrogol, glycerol triacetate, iron oxide red dye, dye iron oxide yellow, dye iron oxide black).

14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pharmacological action

Lipid-lowering drugs, produced by synthetic product of the fermentation Aspergillus tereus. Laktonom is inactive, in the body is metabolised education gidroksikislotnogo derivative. The active metabolite ingibiruet g-KOA-reduktazu, enzyme, katalazirujushhij initial reaction from mevalonate education HMG-CoA. Since the conversion of HMG-CoA in mevalonat is an early stage of the synthesis of cholesterol, application of simvastatin is not causing accumulation in the body potentially toxic sterolov. HMG-CoA is easily metabolized to acetyl-CoA, who participates in many processes of synthesis in the body.

Causes downgrading content in plasma TG, LDL, VLDL and total cholesterol (in cases of heterozygous familial and precluded from accompanying forms of hypercholesterolemia, When mixed Hyperlipidemia, When high cholesterol is a risk factor). Adds lpvp and reduces LDL/HDL ratio and total cholesterol/HDL.

Onset of effect – through 2 weeks from the beginning of reception, maximum therapeutic effect was achieved through the 4-6 weeks. The remains for continuing treatment, with a therapy cholesterol gradually returning to the original level.

Pharmacokinetics

Absorption

Absorption simwastatina high. Treated effect “first pass” through the liver. After oral administration, C_max in plasma is approximately 1.3-2.4 h and is reduced by 90% through 12 no.

Distribution

Binding to plasma proteins is approximately 95%.

Metabolism

It is metabolized in the liver, hydrolyses education active derivative – Beta-hydroxyacids, discovered and other active, as well as inactive metabolites.

Deduction

T_1/2 active metabolites is 1.9 no. Write mainly in the faeces (60%) as metabolites. About 10-15% report the news in the inactive form.

Testimony

Hypercholesterolemia:

- Primary Hypercholesterolemia (Type IIA and IIb) with poor diet low in cholesterol and other non-drug interventions (physical activity and weight loss) in patients with increased risk of coronary atherosclerosis;

-combined giperholesterinemia and gipertriglitzeridemia, not adjustable special diet and physical activity.

Coronary artery disease:

-for prevention of myocardial infarction;

-to reduce the risk of death;

-to reduce the risk of cardio-vascular disorders (stroke or transient ischemic attacks);

— to slow the progression of atherosclerosis of the coronary arteries;

-to reduce the risk of revascularization procedures.

Dosage regimen

Prior to the start of treatment Simvastolom^® the patient should assign standard gipoholesterinovu diet, to be followed throughout the course of treatment.

Simwastol^® It should be taken into 1 time / day in the evening, drinking plenty of water.

While taking the drug should not be associated with food intake.

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

At treatment of hypercholesterolemia the recommended dose of Simvastola^® It varies between 10 mg 80 mg 1 time / day in the evening. The recommended initial dose of the drug for patients with hypercholesterolemia is 10 mg. The maximum daily dose – 80 mg.

Changes (selection) the dose should be carried out at intervals of 4 of the week. In most patients the optimal effect is achieved when taking the drug in doses up to 20 mg / day.

At Homozygous Familial Hypercholesterolemia recommended daily dose Simvastola^® is 40 mg 1 times/day or evening 80 mg 3 admission (20 mg in the morning, 20 mg and day 40 mg in the evening).

At treatment of ISCHEMIC HEART DISEASE or high risk of ISCHEMIC HEART DISEASE effective dose Simvastola^® up 20-40 mg / day. Therefore, the recommended initial dose in such patients – 20 mg / day. Changes (selection) the dose should be carried out at intervals of 4 of the week, if necessary, the dose can be increased to 40 mg / day. If the content of LDL is less 75 mg / dL (1.94 mmol / l), total cholesterol – less 140 mg / dL (3.6 mmol / l), drug dose should be reduced.

In elderly patients with kidney failure and mild changes in dosage is not required.

In patients with chronic renal failure (CC<30 ml / min) or receiving ciclosporin, danazol, gemfibrozil or other Fibrates (In addition to fenofibrata), nicotine acid in lipidosnizhajushhih doses (≥1 g / day) at the same time with Simvastolom^®, the maximum recommended dose of Simvastola^® should not exceed 10 mg / day.

Patient, taking amiodarone or Verapamil concomitantly with Simvastolom^®, daily dose of Simvastola^® should not exceed 20 mg.

Side effect

From the digestive system: There may be pain in the abdomen, constipation, flatulence, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increase in liver transaminases, Alkaline phosphatase, CPK.

From the central and peripheral nervous system: asthenic syndrome, headache, dizziness, insomnia, muscle cramps, paresthesia, perifericheskaya neuropathy, blurred vision, dysgeusia.

On the part of the musculoskeletal system: myopathy, myalgia, muscle cramps, weakness; rarely – raʙdomioliz.

From the laboratory parameters: thrombocytopenia, increased erythrocyte sedimentation rate, eozinofilija.

Allergic reactions: fever, breathlessness, angioedema, polymyalgia rheumatica, vasculitis, arthritis, hives, lupus-like syndrome.

Dermatological reactions: photosensitivity, dermahemia; rarely – skin rash, itch, alopecia, dermatomyositis.

Other: tides, anemia, heartbeat, acute renal failure (due to rhabdomyolysis), reduced potency.

Contraindications

- Liver disease in active phase, strong increase in liver enzymes unclear etiology;

- Myopathy;

- Up to 18 years (efficacy and safety have not been established);

-hypersensitivity to simwastatino and other components of the drug (incl. hereditary lactose intolerance);

-hypersensitivity to other drugs statinovogo stimulants (inhibitors of HMG-CoA reductase inhibitors) history.

FROM caution prescribe the drug in patients with chronic alcoholism; After organ transplantation in the therapy immunodepressantami (in connection with heightened risk of rabdomioliza and kidney failure); under conditions, that can lead to the development of explicit violations of the kidney, such as arterial gipotenzia, acute infectious diseases heavy currents, expressed metabolic and endocrine disorders, violations of water-electrolyte balance, surgery (incl. dental) or injury; patients with low or high tone skeletal muscles unclear etiology; epilepsy, liver diseases in history.

Pregnancy and lactation

Simwastol^® contraindicated in pregnancy. There have been reports of development anomalies in newborns, mothers who took simvastatin in pregnancy.

Women of childbearing age, receiving simvastatin, should avoid conception. Use Simvastola^® It is not recommended for women of childbearing age, do not use contraceptives.

Because, that inhibitors of HMG-CoA reductase inhibitors inhibit the synthesis of cholesterol, and cholesterol and other synthesis products play a significant role in the development of the fetus, including the synthesis of steroids and cell membranes, simvastatin can have adverse effects on the fetus when it is assigned to pregnant. If pregnancy was achieved during treatment, the drug must be cancelled, and the woman warned of the possible danger to the fetus.

Cancellation of lipid means during pregnancy have no significant impact on the results of treatment of primary hypercholesterolemia.

Unknown, whether simvastatin is excreted in breast milk. If necessary, the appointment of Simvastola^® during the lactation period should take into account, that many medicines made with breast milk, and there is a threat to development of severe reactions, Therefore, breast-feeding while taking the drug is not recommended.

Cautions

Simwastol^®, like other inhibitors of HMG-CoA reductase inhibitors, It should not be at high risk of rabdomioliza and kidney failure (against the backdrop of severe acute infections, hypotension, planned a big surgery, injuries, severe metabolic disorders).

At the beginning of therapy Simvastolom^® possible transient increased liver enzymes.

Before therapy and regularly should undertake a study of the liver (control the activity of liver enzymes every 6 weeks within the first 3 Months, then every 8 weeks for the remainder of the first year, and then 1 semi-annually), also if the dose drug should be test for determination of liver. If the dose to 80 mg should be carried out every test 3 of the month. The steady increase in transaminaz (in 3 compared with a baseline) Welcome Simvastola^® discontinue.

In patients with hypothyroidism or if there is some kidney diseases (nephrotic syndrome) If you increase your cholesterol levels should first carry out the main disease therapy.

Simwastol^® be wary appoint patients with chronic alcoholism and/or have a history of liver disease.

Before and during the treatment, the patient should be on gipoholesterinovoj diet.

Simultaneous intake of grapefruit juice can increase the severity of side effects, associated with the acquisition of Simwastol^®, Therefore, you should avoid their simultaneous reception.

Simwastol^® not shown in cases, When there is gipertriglitzeridemia I, Type IV and V.

Treatment Simvastolom^® can cause myopathy, resulting in rabdomiolizu and renal failure. The risk of this pathology is increasing in patients, receiving simultaneously with Simwastol^® one or more of the following medicines: fibrates (gemfibrozil, fenofibrate), cyclosporine, nefazodon, makrolidы (Erythromycin, clarithromycin), antifungal agents from the group of azoles (ketoconazole, itraconazole) and HIV protease inhibitors (ritonavir). The risk of myopathy is increased also in patients with severe renal insufficiency. All patients, Beginners therapy Simwastol^®, and patients, who need to increase the dose of the drug, should be warned about the potential for myopathy and need immediate treatment to a doctor in case of unexplained pains, soreness in muscles, lethargy or muscle weakness, especially if it's accompanied by malaise or fever. Drug therapy should be immediately discontinued, If myopathy is diagnosed or suspected.

With a view to the timely diagnosis of myopathy during treatment it is recommended to regularly determine the activity of KFK.

When treating Simvastolom^® possible increase of serum CPK, that should be taken into account in the differential diagnosis of pain behind the breast bone. Criterion of the drug provides increase of CPK in the blood serum of more than 10 times concerning the VGN. In patients with myalgia, myasthenia and/or expressed by increased activity of KFK treatment with stop.

Simwastol^® effective as monotherapy, and in combination with bile acid sekvestrantami.

If this passes doses the drug should be taken as soon as possible. If it is time to receive the next dose, dose not doubling.

Treatment of patients with severe renal insufficiency are under the control of the kidney.

Effects on ability to drive vehicles and management mechanisms

The adverse effect of Simvastola^® the ability to manage and work with mechanisms not reported.

Overdose

None of the few known cases of overdose (maximum accepted dose 450 mg) specific symptoms were not revealed.

Treatment: , induce vomiting, assign activated carbon; if necessary, symptomatic therapy. Should monitor liver and kidneys, level of CPK in blood serum.

With the development of MYO with rhabdomyolysis is a and acute renal failure (rare, but severe side effects) You should immediately discontinue use of the drug, assign a diuretic and sodium bicarbonate (in / in infusion). Optionally shows the hemodialysis.

Rhabdomyolysis can cause giperkaliemia, that can be addressed in/with the introduction of calcium chloride or calcium glukonata, infusion of dextrose (Glucose) with insulin, use of potassium ion exchange products or, in severe cases, using hemodialysis.

Drug Interactions

The risk of myopathy is increased while applying Simvastola^® with one or more of the following medicines: cytostatics, fibrates, immunosuppressants, nefazodon, Erythromycin, clarithromycin, antifungal agents from the group of azoles (incl. ketoconazole, itraconazole), HIV protease inhibitors, high doses of nicotinic acid, telithromycin.

Together with the use of high doses of simvastatin with ziklosporinom or danazolom the risk of myopathy/rhabdomyolysis is increased.

The risk of myopathy is increased with a joint appointment with other lipid means, who are not powerful inhibitors izofermenta CYP3A4, but can cause myopathy in conditions alone. Like gemfibrozil and other Fibrates (In addition to fenofibrata), as well as niacin dose of ≥ 1 g/d.

The risk of myopathy is increased when amiodarone or Verapamil with simvastatinom in high doses.

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

Simvastatin potentiates the action of oral anticoagulants (incl. fenprokumona, varfarina) and increases the risk of bleeding. In this regard, to control blood coagulability before treatment, as well as often enough during the initial period of therapy. Once achieved a stable level of prothrombin time or MPE, further control should be spacing, recommended for patients, receiving anticoagulant therapy. When you change the dose or discontinuing simvastatin should also conduct monitoring protrombinovogo time or MPE for the above schema.

Simvastatinom therapy does not cause changes in prothrombin time and the risk of bleeding in patients, do not take anticoagulants.

Simvastatin improves the level of Digoxin in plasma.

Cholestyramine and colestipol reduce bioavailability (application of simvastatin may through 4 hours after taking these medicines, with additive effect).

Grapefruit juice contains one or more components, that inhibit CYP CYP3A4 and may increase concentration in plasma preparations, metaboliziruthan with participation of CYP3A4. Increased activity of inhibitors of HMG-CoA reductase inhibitors after taking 250 ml of juice a day is minimal and has no clinical significance. However, consumption of large amount of juice (more 1 liters per day) When taking simvastatin significantly increases the level of inhibiting activity against HMG-CoA reductase inhibitors in blood plasma. In this regard, the need to avoid grapefruit juice in large quantities.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 25 ° C. Shelf life - 3 year.