Simvastatin pills 20mg №30

Dosage form

Film Coated Tablets

Composition

1 tablet, film coated contains:
active substances: simvastatin 20 mg

Packing

30 tablets

Mechanism of action

Simvastatin - a hypolipidemic agent, obtained synthetically from the fermentation product Aspergillus terreus, is an inactive lactone, in the body it undergoes hydrolysis to form 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 the formation of mevalonate from HMG-CoA. Since the transformation of HMG-CoA into 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 processes of synthesis in the body.

It 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-familial forms of hypercholesterolemia, with mixed hyperlipidemia, when elevated cholesterol is a part of the disease, the factor of hypercholesterolemia, with mixed hyperlipidemia, when the high content of cholesterol is a part of the disease, is one of the most important factors in hypercholesterolemia, with mixed hyperlipidemia, when high content of cholesterol is a factor..

Increases the content of high-density lipoprotein (HDL) and reduces the ratio of LDL / HDL and total cholesterol / HDL.

The beginning of the manifestation of the effect - after 2 weeks from the start of the reception, the maximum therapeutic effect is achieved after 4-6 weeks. The effect persists with continued treatment, with the cessation of therapy, the cholesterol content gradually returns to its original level.

Absorption is high. After ingestion C_max in blood plasma is reached in about 1.3-2.4 hours and decreases by 90% in 12 hours. Binding to plasma proteins is about 95%.

Metabolized in the liver, has the effect of "first pass" through the liver (hydrolyzes to form an active derivative: beta-hydroxy acids, other active, as well as inactive metabolites are found). T_1/2 active metabolites is 1.9 h.

Excreted mainly with feces (60%) in the form of metabolites. About 10-15% is excreted by the kidneys in an inactive form.

Indications and usage

Hypercholesterolemia:

• primary hypercholesterolemia (type IIa and IIb) with the ineffectiveness of diet therapy with low cholesterol and other non-drug interventions (exercise and weight loss) in patients with an increased risk of coronary atherosclerosis;
• combined hypercholesterolemia and hypertriglyceridemia, not corrected by a special diet and exercise.

Coronary heart disease:

• for the prevention of myocardial infarction,
• to reduce the risk of death
• reduce the risk of cardiovascular disorders (stroke or transient ischemic attacks),
• slowing the progression of atherosclerosis of the coronary vessels,
• reduce the risk of revascularization procedures.

Contraindications

• liver disease in the active phase, a persistent increase in liver enzymes of unknown etiology;
• skeletal muscle diseases (myopathy);
• age up to 18 years (efficacy and safety not established);
• hypersensitivity to simvastatin or to other components of the drug (including hereditary lactose intolerance), as well as to other statin drugs (inhibitors of HMC-CoA reductase) in history.

WITH caution prescribed to patients with alcohol abuse, patients after organ transplantation, which is treated with immunosuppressants (due to the increased risk of rhabdomyolysis and renal failure); in conditions that can lead to the development of severe kidney function deficiency, such as arterial hypotension, acute severe infectious diseases, pronounced metabolic and endocrine disorders, impaired water and electrolyte balance, surgical intervention (including dental) or injury; patients with reduced or elevated skeletal muscle tone of unknown etiology; epilepsy.

Pregnancy and Breastfeeding

Simvastatin may have an adverse effect on the fetus and is contraindicated in pregnant women. There are several reports of the development of anomalies in newborns whose mothers took simvastatin.

Women of reproductive age who take simvastatin should avoid conception. The use of simvastatin is not recommended for women of childbearing agenon-contraceptive use. If, in the course of treatment, the pregnancy nevertheless occurs, Simvastatin should be canceled and the woman should be warned of the possible danger to the fetus.

Data on the allocation of Simvastatin with breast milk are not available. If necessary, the appointment of Simvastatin during lactation should take into account that many drugs are excreted in breast milk, and there is a risk of severe reactions, so breastfeeding while taking the drug is not recommended.

Dosage and administration

Before starting treatment with simvastatin, the patient should be prescribed a standard hypocholesterol diet, which should be followed during the entire course of treatment.
Simvastatin should be taken orally once a day in the evening, drinking plenty of water.

Drug intake time should not be associated with food intake.
The recommended dose of simvastatin for the treatment of hypercholesterolemia varies from 10 to 80 mg 1 time per day in the evening. The recommended starting dose for patients with hypercholesterolemia is 10 mg.The maximum daily dose is 80 mg.
Changes (selection) 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 daily dose of simvastatin is 40 mg 1 time / day in the evening or 80 mg in 3 doses (20 mg in the morning, 20 mg in the afternoon and 40 mg in the evening).

When treating patients with coronary heart disease (CHD) or at high risk of developing CHD, the effective doses of simvastatin are 20-40 mg / day. Therefore, the recommended initial dose in such patients is 20 mg / 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 / day. If the content of LDL 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.

In elderly patients and in patients with mild or moderately severe renal failure no change in dosage of the drug is required.
In patients with chronic renal failure (creatinine clearance less than 30 ml / min) or receiving cyclosporine, danazol, gemfibrozil or other fibrates (except fenofibrate), 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 taking Amiodarone or Verapamil simultaneously with simvastatin, the daily dose should not exceed 20 mg.

Adverse reactions

From the digestive system: possible abdominal pain, constipation, flatulence, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increased activity of liver enzymes, alkaline phosphokinase and creatine phosphokinase (CPK).

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

Musculoskeletal system: myopathy, myalgia, muscle cramps, weakness; rarely - rhabdomyolysis.

Allergic and immunopathological reactions: angioedema, rheumatic polymyalgia, vasculitis, thrombocytopenia, increased ESR, fever, arthritis, urticaria, photosensitization, skin flushes, hot flashes, shortness of breath, lupus-like syndrome, eosinophilia.

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

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

At the beginning of therapy with simvastatin, a transient increase in liver enzymes is possible.
Before starting therapy and then regularly conduct a study of the liver (monitor the activity of liver enzymes every 6 weeks for the first 3 months, then every 8 weeks for the remaining first year, and then once every six months), as well as with increasing doses should be tested to determine liver function.If you increase the dose to 80 mg, you need to test every 3 months. With a persistent increase in the activity of transaminases (3 times compared with the initial level), the administration of Simvastatin should be stopped.

Simvastatin, like other inhibitors of HMG-CoA reductase, should not be used with an increased risk of developing rhabdomyolysis and renal failure (against the background of severe acute infection, hypotension, planned major surgery, trauma, severe metabolic disorders).
Cancellation of hypolipidemic drugs during pregnancy does not have a significant impact 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 an increase in cholesterol level, the therapy underlying the disease should first be carried out.
Simvastatin is prescribed with caution to persons who abuse alcohol and / or have a history of liver disease.

Before and during treatment, the patient should be on a cholesterol diet.
The simultaneous intake of grapefruit juice can increase the severity of side effects associated with the intake of simvastatin, so their simultaneous intake should be avoided.

Simvastatin is not indicated in cases where there is hypertriglyceridemia I, IV and V types.
Treatment with simvastatin can cause myopathy, leading to rhabdomyolysis and renal failure.The risk of this pathology increases in patients receiving one or more of the following drugs simultaneously with Simvastatin: fibrates (gemfibrozil, fenofibrate), cyclosporine, nefazadone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of azoles (ketoconazole, itraconazole) and HIV proteases (ritonavir). The risk of myopathy is also increased in patients with severe renal failure.
All patients starting therapy with 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 for immediate medical attention in case of unexplained pain, muscle soreness, lethargy or muscle weakness, especially if this is accompanied by indisposition or fever. Drug therapy should be immediately discontinued if myopathy is diagnosed or contemplated.

In order to diagnose the development of myopathy, it is recommended to regularly measure CPK values.
When treating with Simvastatin, an increase in the serum CPK content is possible, which should be taken into account in the differential diagnosis of chest pain. The criterion for discontinuation of the drug is an increase in the content of CK in the serum of more than 10 times relative to the upper limits of the norm. In patients with myalgia, myasthenia and / or a pronounced increase in the activity of CPK, treatment with the drug is stopped.
The drug is effective both in the form of monotherapy, and in combination with bile acid sequestrants.

In case of missing the current dose, the drug should be taken as soon as possible. If the time for the next dose has arrived, do not double the dose.
Patients with severe renal insufficiency are treated under the control of renal function.
The duration of the drug is determined by the attending physician individually.
Influence on ability to drive motor transport and control mechanisms
No adverse effects of the drug on the ability to drive and work with mechanisms were reported.

Cytostatics, antifungal agents (ketoconazole, 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 co-administration of cyclosporine or danazol with high doses of simvastatin.

Other hypolipidemic agents that can cause the development of myopathy: the risk of developing myopathy increases with the joint appointment of other lipid-lowering drugs that are not potent inhibitors of CYP3A4 , but are able to induce myopathy in monotherapy. Such as gemfibrozil and other fibrates (except fenofibrate), as well as nicotinic acid in a dose of ≥ 1 g per day.

Amiodarone and verapamil: the risk of myopathy increases with co-administration of amiodarone or verapamil with high doses of simvastatin.

Diltiazem: the risk of myopathy is slightly increased in patients receiving diltiazem simultaneously with Simvastatin at a dose of 80 mg.

Simvastatin potentiates action oral anticoagulants (for example, fenprocumon, warfarin) and increases the risk of bleeding, which requires the need to monitor blood clotting indicators prior to treatment, as well as quite often in the initial period of therapy. Once a stable level of prothrombin time or the International Normalized Relationship (INR) is achieved, its further monitoring should be carried out at intervals recommended for patients receiving anticoagulant therapy. When changing the dosage or discontinuation of Simvastatin, the prothrombin time or INR should also be monitored as described above.

Simvastatin therapy does not cause changes in prothrombin time and the risk of bleeding in patients not taking anticoagulants.

Level up digoxin in blood plasma.

Kolestiramin and Kolestipol reduce bioavailability (use of Simvastatin is possible 4 hours after taking these medicines, with an additive effect).

Grapefruit juice contains one or more components that inhibit CYP3A4 and may increase the plasma concentration of drugs metabolized by CYP3A4.The 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, consuming a large volume of juice (more than 1 l per day) while taking Simvastatin significantly increases the level of inhibitory activity against HMG-CoA reductase in plasma. In this regard, it is necessary to avoid the consumption of grapefruit juice in large quantities.

None of the known several cases of overdose (maximum dose of 450 mg) revealed any specific symptoms.
Treatment: induce vomiting, take activated charcoal, conduct symptomatic therapy. Liver and kidney function, serum CK levels should be monitored.
With the development of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), the drug should be stopped immediately and a diuretic and sodium bicarbonate should be given to the patient (intravenous infusion). If necessary, hemodialysis is indicated.
Rhabdomyolysis can cause hyperkalemia, which can be eliminated by intravenous administration of Calcium chloride or Calcium gluconate , infusion of glucose with insulin , using potassium ion exchange sorbents or, in severe cases, by hemodialysis.

In a dry, dark place at a temperature not higher than 25 ° C. Keep out of the reach of children.