SIMVASTATIN PILLS 10MG

Mechanism of action

The lipid-lowering agent, obtained synthetically from the fermentation product Aspergillus terreus, is an inactive lactone, undergoes hydrolysis in the body 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 to form mevalonate from HMG-CoA. Since the transformation of HMG-CoA into mevalonat is an early stage of cholesterol synthesis, 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.

Simvastatin 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 there is an increased ) due to the inhibition of cholesterol synthesis in the liver and an increase in the number of LDL receptors on the cell surface, which leads to increased capture and catabolism of LDL.

Increases the content of high-density lipoprotein (HDL) and reduces the ratio of LDL / HDL and total cholesterol / HDL. Does not have a mutagenic effect.

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; at the termination of therapy the content of cholesterol gradually returns to the original level.

Pharmacokinetics

Absorption - high, bioavailability - less than 5%. After oral administration, TCmax - 1.3-2.4 h and decreases by 90% after 12 h. Communication with plasma proteins is about 95%.

Enters the body in an inactive form. It is hydrolyzed in tissues into its active form - beta-hydroxy acid and inactive metabolites.

Metabolized in the liver, has the effect of "first pass" through the liver. CYP3A4, CYP3A5 and CYP3A7 isoenzymes are involved in the metabolism of simvastatin.

T1/2 active metabolites is 1.9 hours. Excreted mainly through the intestines (60%) as metabolites. About 10-15% is excreted by the kidneys in an inactive form.

Indications

Hypercholesterolemia:

- primary hypercholesterolemia (heterozygous familial and nonfamily, types IIa and IIb and mixed according to the Fredrickson classification) with the ineffectiveness of diet therapy with low cholesterol and other non-drug measures (exercise and weight loss) in patients with increased risk of coronary atherosclerosis;

- combined hypercholesterolemia and hypertriglyceridemia, which is not corrected by a special diet and exercise.

Coronary heart disease:

- secondary prevention in order to reduce the overall risk of death, myocardial infarction (to slow the progression of coronary atherosclerosis), stroke and transient cerebral circulatory disorders, reducing the risk of revascularization procedures.

Dosage and administration

Before 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 duration of the drug is determined by the attending physician individually.

Hypercholesterolemia

The recommended dose of Simvastatin for treatmenthypercholesterolemiavaries from 5 to 80 mg once a day in the evening.

With the ineffectiveness of the drug in a dose of 40 mg is recommended to switch to another type of lipid-lowering therapy. The use of the drug in a dose of more than 40 mg increases a significant risk of myopathy.

The dose of Simvastatin 80 mg should be used only in those patients who have not reached the target concentration of LDL when using a dose of 40 mg.

The recommended starting dose for patients with hypercholesterolemia is 10 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 per day.

In patients with homozygous hereditary hypercholesterolemiaThe recommended daily dose of Simvastatin is 40 mg (2 pills of 20 mg once daily 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). These patients are recommended to use Simvastatin in combination with another lipid-lowering therapy (for example, LDL apheresis).

Coronary heart disease

When treating patients with ischemic heart disease (CHD) or high risk of developing CHD, with or without hyperlipidemia, effective doses of the drug Simvastatin are 20, 40 mg per day. Therefore, the recommended initial dose in such patients is 20 mg per day. Changes (selection) dose should be carried out at intervals of 4 weeks, if necessary, the dose can be increased to 40 mg per day (2 pills of 20 mg of the drug simvastatin). 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.

Concomitant therapy

In patients receiving treatment with cyclosporine, danazol, gemfibrozil, other fibrates (except fenofibrate) or nicotinic acid in lipid-lowering doses (more than 1 g / day), the recommended maximum daily dose of Simvastatin should not exceed 10 mg. A further dose increase in such situations is not recommended.

For patients simultaneously taking Amiodarone or Verapamil, the daily dose of the drug Simvastatin should not exceed 20 mg.

For patients simultaneously receiving diltiazem, the daily dose of the drug Simvastatin should not exceed 40 mg.

In elderly patients and in patients with mild or moderately severe renal failure dose adjustment of the drug is not required.

In patients with severe renal failure (CC less than 30 ml / min) The recommended dose of the drug Simvastatin should not exceed 10 mg per day. If it is necessary to increase the dose, careful monitoring of such patients is carried out.

Side effect

Gastrointestinal:constipation, abdominal pain, flatulence, dyspepsia, nausea, vomiting, diarrhea, pancreatitis, hepatitis, cholestatic jaundice, abnormal liver function, increased activity of "hepatic" transaminases, alkaline phosphatase and CK.

From the side of the central nervous system and sensory organs:asthenia, headache, paresthesia, dizziness, peripheral neuropathy, insomnia, impaired memory, muscle cramps, blurred vision, impaired taste, myasthenia gravis, weakness.

Musculoskeletal system:myopathy, rhabdomyolysis, myalgia, muscle cramps.

Allergic and immunopathological reactions: expanded hypersensitivity syndrome (angioedema, lupus-like syndrome, rheumatic polymyalgia, vasculitis, dermatomyositis, thrombocytopenia, eosinophilia, increased ESR, arthritis, arthralgia, urticaria, photosensitization, blood flushes to the skin of the face, cloak)

Dermatologic:skin rash, itching, alopecia.

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

Contraindications

- liver disease in the active phase, a persistent increase in the activity of "liver" transaminases of unknown etiology;

- simultaneous administration of cytochrome P450 3A4 inhibitors (CYP3A4 isoenzyme) (for example, itraconazole, Ketoconazole, HIV protease inhibitors, Erythromycin, Clarithromycin, telithromycin and nefazodone);

- Diseases of skeletal muscles (myopathy);

- pregnancy and lactation;

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

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;

- Hypersensitivity to simvastatin or to other components of the drug, as well as to other statin drugs (HMG-CoA reductase inhibitors) in history.

with caution:alcoholism, history of liver disease, severe water and electrolyte imbalance, marked endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), myopathy, acute necrosis of skeletal muscles, uncontrolled epilepsy, extensive surgical interventions, trauma; simultaneous administration with gemfibrozil and other fibrates (except fenofibrate) cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), amiodarone, verapamil, diltiazem, grapefruit juice; severe renal failure (CC less than 30 ml / min); old age (over 65, especially women), impaired renal function.

Use during pregnancy and lactation

Simvastatin may have an adverse effect on the fetus and is contraindicated for use 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 the drug simvastatin is not recommended for women of childbearing age who do not use reliable methods of contraception.

If, in the course of treatment, the pregnancy does occur, 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 breastfeeding should be borne in mind that many drugs are excreted in breast milk, and there is a risk of severe reactions, so breastfeeding while taking the drug should be stopped.

Application for violations of the liver

Contraindications: liver disease in the active phase, a persistent increase in liver enzymes of unknown etiology.

With caution: a history of liver disease.

Application for violations of kidney function

With care: severe renal failure (CC less than 30 ml / min); impaired renal function.

In patients with severe renal insufficiency (CC less than 30 ml / min), the recommended dose of Simvastatin should not exceed 10 mg per day.If it is necessary to increase the dose, careful monitoring of such patients is carried out.

Patients with mild or moderate renal insufficiency do not require dose adjustment.

Use in children

Contraindicated in children under 18 years.

Use in elderly patients

Prescribe with care to the elderly (over 65, especially women).

Elderly patients do not require dose adjustment.

special instructions

At the beginning of therapy with simvastatin, a transient increase in the level of liver enzymes is possible.

Before starting therapy and continue to conduct regular liver function tests (monitor liver enzyme activity after 6 weeks for the first 3 months, then after 8 weeks for the remaining first year, and then once every six months), also with increasing doses, a test should be performed on determination of liver function. If you increase the dose to 80 mg, you need to test after 3 months. With a persistent increase in transaminase activity (3 times compared with the initial level), the administration of simvastatin should be stopped.

Simvastatin, like other HMG-CoA reductase inhibitors, should not be used with an increased risk of developing rhabdomyolysis and renal failure (against the background of severe acute infection, hypotension, trauma, planned major surgery, 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 must 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, intraconazole), intraconazole, and antifungal agents from the group of azoles (ketoconazole, intraconazole), antifungal agents from the group of azoles (ketoconazole, intraconazole), antifungal agents from the group of azoles (ketoconazole, intraconazole), antifungal agents from the group of azoles (ketoconazole, intraconazole), and intraconazole) and HIV proteases (ritonavir). The risk of myopathy also increases in patients with severe renal insufficiency.

Among the predisposing factors for the development of myopathy, there is an elderly age (over 65), female identity, uncontrolled hypothyroidism, and 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 pain, lethargy or muscle weakness, especially if this is accompanied by indisposition or fever. Product 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.