Expiration date: 03/2025

Composition

Simvastatin tablets Zentiva, film-coated from white to almost white, oblong, biconvex, with valium on both sides and engraved with "SVT" and "10", "20" or "40" on one of the sides.

1 tablet contains: simvastatin 10, 20 or 40 mg

Excipients: lactose 298 mg corn starch pregelatinization 40 mg, microcrystalline cellulose - 20 mg talc 4 mg magnesium stearate 2 mg, butylhydroxyanisole - 0.08 mg.

Pharmaceutical action

A lipid lowering drug from the group of statins.

Simvastatin is prepared synthetically from fermentation product of Aspergillus terreus.

Is an inactive lactone, the body is subjected to hydrolysis with the formation of gidrokshikislota derived. The active metabolite ingibiruet g-Koa-reductase, the enzyme catalyzing the initial reaction of formation of mevalonate from HMG-COA.

Causes a decrease in the concentration of plasma TG, LDL, 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 the concentration of HDL and reduces the ratio of LDL/HDL and total cholesterol/HDL.

The onset of effect within 2 weeks from the beginning of reception, the maximum therapeutic effect is achieved after 4-6 weeks. The effect persists with continued treatment, at the termination of therapy cholesterol gradually returning to the initial level.

Indications:

Hyperlipidemia:

• primary hypercholesterolemia (type IIA and IIb according to Frederickson) gipoholesterinova with the ineffectiveness of diet and other non-drug measures 
  
• (physical activity and weight loss) in patients with increased risk 
  
• the occurrence of coronary atherosclerosis
  
• combined giperholesterinemia and gipertriglitzeridemia, 
  
• not amenable to correction special diet and physical exercise.
  

Coronary artery disease:

• for prevention of myocardial infarction, to reduce the risk of total mortality reduce the risk of cardiovascular disorders (stroke or transient ischemic attacks), slowing progression coronary atherosclerosis, reduce the risk of the revascularization, with both normal and elevated cholesterol.
  

Pregnancy

Contraindicated in pregnancy.

In the case of confirmation of pregnancy in the process of drug therapy Zentiva Simvastatin, the drug should be discontinued immediately, and patients to warn of the potential risk to the fetus.

Use in women of reproductive age is possible only if you use reliable methods of contraception and the patient should be informed 

about the possible risk to the fetus.

The use of the drug during the breastfeeding period, given the potential for adverse events in nursing infants, discontinue.

Contraindications:

• liver disease in the active phase, persistent increase in liver transaminaz ambiguous Genesis,
  
• concomitant use of powerful inhibitors CYP3A4
  
• (e.g., Itraconazole, ketoconazole, Posaconazole, HIV protease inhibitors, erythromycin, clarithromycin, and nefazodone telithromycin),
  
• concomitant treatment with gemfibrozil, cyclosporine or danazol,
  
• pregnancy,
  
• lactation (breast-feeding),
  
• the age 18 years (effectiveness and safety have not been established),
  
• hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption,
  
• hypersensitivity to the drug component Simvastatin Zentiva,
  
• hypersensitivity to other drugs statinovogo series (inhibitors of HMG-COA reductase inhibitors) in history.
  

With caution is prescribed to patients with sustained increased activity of hepatic transaminases (more than 3 times compared with CAH), patients who abuse alcohol, patients after organ transplantation who have undergone the therapy immunodepressantami (due to the increased risk of rabdomioliza and kidney failure), at the conditions that can lead to the development of severe renal insufficiency, such as hypotension, acute infectious diseases heavy currents, expressed metabolic and endocrine disorders, violations vodno-elektrolitnogo balance, surgical interventions (including dental surgery) or trauma, patients with low or high tone skeletal muscles unclear etiology, epilepsy, when administered simultaneously with fibrates (except a gemfibrozil fenofibrate), nicotinic acid lipidnami doses (more 1 g/day), amiodarone, verapamil, amlodipine, diltiazem, fusidic acid, grapefruit juice, severe renal failure, patients with diabetes mellitus.

Dosing

Before prescribing medication the patient should be encouraged gipoholesterinovu standard diet which it should observe during the entire period of therapy.

The drug is taken orally 1 times/day. in the evening, squeezed enough water.

The drug should not be linked with food intake.

The recommended dose of the drug Simvastatin Zentiva for the treatment of hypercholesterolemia varied from 5 to 80 mg 1 times/day. in the evening. The recommended initial dose for patients with hypercholesterolemia, is 10-20 mg/day. The maximum daily dose - 80 mg. 

The dose of 80 mg/day. it is recommended to appoint only in case, if the treatment at lower doses did not allow to achieve certain goals of therapy

and expected benefit from treatment exceeds the potential risk. Change (selection) the dose should be carried out at intervals of 4 weeks. In most patients the optimal effect is achieved when taking the drug in doses up to 20 mg/day.

In patients with homozygous hereditary hypercholesterolemia the recommended dose is Simvastatin Zentiva 40 mg 1 times/day. in the evening or 80 mg 3 reception (20 mg morning, 20 mg day and 40 mg in the evening). The dose of 80 mg/day. it is recommended to appoint only in case, if the treatment at lower doses did not allow to achieve certain goals of therapy and the expected benefit from treatment exceeds the potential risk.

In the treatment of patients with CHD or high risk for coronary heart disease effective dose of the drug Simvastatin Zentiva amount to 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 weeks, the dose can be increased to 40 mg/day.If the content of LDL cholesterol less than 75 mg/DL (1.94 mmol/l), total cholesterol - less than 140 mg/DL (3.6 mmol/l), the dose should be reduced.

In elderly patients and in patients with renal insufficiency or moderate changes of dose is not required. In patients with chronic renal insufficiency (CC <,,30 1="" 10="" br="">,, For patients taking amiodarone or verapamil simultaneously with the Zentiva drug Simvastatin daily dose Simvastatin Zentiva should not exceed 20 mg.

For patients taking diltiazem or amlodipine simultaneously with the Zentiva drug Simvastatin daily dose Simvastatin Zentiva should not exceed 40 mg.

If you skip doses of the drug must be taken as soon as possible. If it is time for your next dose, double dose is not recommended.

Side effects

The liver and biliary tract: rarely - hepatitis, jaundice.

CNS: rarely - headache, dizziness, paresthesia, insomnia, peripheral neuropathy, rarely - impaired memory, depression.

From the side of respiratory system: very rarely - interstitial lung disease. With the appearance in patients of the symptoms of lung disease (shortness of breath, non-productive cough) on the background of General symptoms (fatigue, weight loss), you need to stop taking the drug and consult a specialist.

From the sensory organs: rarely - blurred vision, 

a violation of taste sensations.

From the skin: rarely - skin rash, itching, alopecia, dermatomyositis.

From the side of musculoskeletal system: rare - myopathy, myalgia,

muscle cramps, rhabdomyolysis.

With the hematopoietic system: rarely - anemia.

Allergic and immunopathological reactions: rare - angioneurotic edema, rheumatic polimialgia, vasculitis, arthritis, urticaria, volchanochnopodobny syndrome.

Other: rarely - palpitations, "tides" of blood to the face, weakness, fever, shortness of breath, skin flushing, photosensitivity, asthenia, acute renal failure (due to rhabdomyolysis), low potency.

Overdose:

None of the few known cases of overdose

(the maximum accepted dose 3.6 g) specific symptoms have been identified.

Treatment: gastric lavage, administration of activated charcoal. Symptomatic therapy. 

Interaction

Cytostatics, antifungal agents (ketoconazole, Itraconazole, Posaconazole), fibrates, immunosuppressants, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone when administered together with simvastatin increase the risk of myopathy.

The risk of myopathy/rhabdomyolysis is increased when administered together with cyclosporine or danazol, high doses of simvastatin.

The risk of myopathy is increased with a joint appointment with other lipid-lowering drugs that are not potent inhibitors of CYP3A4, but can cause myopathy in monotherapy conditions, such as gemfibrozil and other fibrates (except phenofibrate), and nicotinic acid in Lipetskaya doses (more 1 g/day).

The risk of myopathy increases with coadministration of amiodarone or verapamil with high doses of simvastatin.

The risk of myopathy is increased when co-administered fusidic acid and statins. 

The risk of myopathy/rhabdomyolysis is increased when administered together colchicine and simvastatin.

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

Simvastatin increases the concentration of digoxin in plasma.

Cholestyramine and colestipol reduce the bioavailability of simvastatin (simvastatin may apply after 4 hours after taking the medicines, while there is an additive effect).

Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the concentration in blood plasma means metabolized by CYP3A4. Increased activity of inhibitors of HMG-COA reductase after drinking 250 ml of juice a day is minimal and has no clinical significance. 

However, the use of a large amount of juice (more 1 l a day) while taking simvastatin significantly increases the level of inhibitory activity against HMG-COA reductase in the blood plasma. In this regard, you must avoid drinking grapefruit juice in large quantities on the background of therapy with simvastatin.