Simvastatin - instructions for use, reviews of statin, analogs and form of release (tablets 10 mg, 20 mg and 40 mg) drugs for the treatment of hypercholesterolemia and lowering cholesterol in adults, children and pregnancy

In this article, you can read the instructions for using the drug Simvastatin. There are reviews of visitors to the site - consumers of this medication, as well as opinions of specialists on the use of Simvastatin in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Simvastatin analogues in the presence of existing structural analogues. The use of statin to treat hypercholesterolemia and reduce cholesterol in adults, children, as well as in pregnancy and lactation.

Simvastatin - a lipid-lowering agent obtained synthetically from the fermentation product Aspergillus terreus, is an inactive lactone, in the body it undergoes hydrolysis with the formation of 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 mevalonate formation 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.

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-family forms of hypercholesterolemia, with mixed hyperlipidemia, when elevated cholesterol is a risk factor ) by inhibiting the synthesis of cholesterol in the liver and increasing the number of LDL receptors on the surface of cells, which leads to increased capture and catabolism of LDL.

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

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 action is preserved when the treatment is continued; When the therapy is stopped, the cholesterol content gradually returns to the initial level.

Composition

Simvastatin + excipients.

Pharmacokinetics

Absorption is high, bioavailability is less than 5%. The connection with plasma proteins is about 95%. It enters the body in an inactive form. Hydrolyses 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. It is excreted primarily through the intestine (60%) in the form of metabolites. About 10-15% is excreted by the kidneys in an inactive form.

Indications

Hypercholesterolemia

• primary hypercholesterolemia (heterozygous family and non-familial, types 2a and 2b and mixed according to Fredrickson classification) with ineffectiveness of diet with low cholesterol and other non-medicinalmeasures (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

• secondary prophylaxis to reduce the overall risk of death, myocardial infarction (to slow the progression of coronary atherosclerosis), stroke and transient cardiovascular disorders, reduce the risk of revascularization procedures.

Forms of release

Tablets 10 mg, 20 mg and 40 mg.

Instructions for use and dosage

Before the treatment with simvastatin, the patient should be prescribed a standard hypocholesterolemic diet, which should be observed throughout the course of treatment.

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

The time of taking the drug should not be associated with eating. Duration of the drug is determined individually by the attending physician.

Hypercholesterolemia

The recommended dose of the drug Simvastatin for the treatment of hypercholesterolemia varies from 5 to 80 mg once a day in the evening.

If the drug is ineffective at a dose of 40 mg, it 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 the significant risk of myopathy.

The dosage of Simvastatin 80 mg should be used only in those patients who did not reach the target LDL concentration with a dose of 40 mg.

The recommended initial dose of the drug for patients with hypercholesterolemia is 10 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 of Simvastatin is 40 mg (2 tablets of 20 mg once a day in the evening or 80 mg in 3 divided doses (20 mg in the morning, 20 mg in the afternoon and 40 mg in the evening) .This patients are recommended to use simvastatin in combination with other lipid-lowering therapy (for example, apheresis of LDL).

Cardiac ischemia

In the treatment of patients with coronary heart disease (CHD) or a high risk of developing coronary artery disease, with or without hyperlipidemia, effective doses of Simvastatin 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 done at intervals of 4 weeks, if necessary, the dose can be increased to 40 mg per day (2 tablets of 20 mg of simvastatin). 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.

Concomitant therapy

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

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

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

In elderly patients and in patients with mild or moderate renal insufficiency, dose adjustment is not required.

In patients with severe renal failure (CK 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.

Side effect

• constipation;
• stomach ache;
• flatulence;
• dyspepsia;
• nausea, vomiting;
• diarrhea;
• pancreatitis;
• hepatitis;
• cholestatic jaundice;
• abnormal liver function;
• asthenia;
• headache;
• paresthesia;
• dizziness;
• peripheral neuropathy;
• insomnia;
• memory impairment;
• muscle cramps;
• blurred vision;
• a violation of taste sensations;
• myasthenia gravis;
• weakness;
• myopathy;
• rhabdomyolysis;
• myalgia;
• muscle cramps;
• developed syndrome of hypersensitivity (angioneurotic edema, lupus-like syndrome, rheumatic polymyalgia, vasculitis, dermatomyositis, thrombocytopenia, eosinophilia, increased ESR, arthritis, arthralgia, urticaria, photosensitization, "tides" of blood to the skin of the face, dyspnea);
• skin rash;
• itching;
• alopecia;
• anemia;
• a feeling of palpitations;
• acute renal failure (due to rhabdomyolysis);
• decreased potency.

Contraindications

• liver disease in the active phase, persistent increase in the activity of "liver" transaminases of unclear etiology;
• simultaneous administration of cytochrome P450 3A4 inhibitors (isoenzyme CYP3A4) (eg, itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone);
• diseases of skeletal muscles (myopathy);
• pregnancy and lactation;
• age under 18 years (effectiveness and safety not established);
• deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome;
• increased susceptibility to simvastatin or to other components of the drug, as well as to other drugs of the statin series (inhibitors of HMG-CoA reductase) in the anamnesis.

Application in pregnancy and lactation

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 were taking simvastatin.

Women of reproductive age who take simvastatin should avoid conception. The use of simvastatin is not recommended in women of childbearing age who do not use reliable methods of contraception.

If during pregnancy the pregnancy is still there, simvastatin should be canceled,and a 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 appoint simvastatin during breastfeeding, it should be borne in mind that many drugs are excreted in breast milk and there is a threat of development of severe reactions, so breast-feeding during drug intake should be discontinued.

Application in elderly patients

Prescribe with caution elderly people (over 65, especially women).

In elderly patients, dose adjustment is not required.

Use in children

Contraindicated in children under 18 years.

special instructions

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

Before the beginning of therapy, and further regularly carry out a study of liver function (to monitor the activity of liver enzymes after 6 weeks during the first 3 months, then 8 weeks during the remaining first year, and then 1 time in six months), and with increasing doses, determination of liver function. When the dose is raised to 80 mg, the test should be performed after 3 months.With a persistent increase in the activity of transaminases (3-fold compared with baseline), the intake of simvastatin should be discontinued.

Simvastatin, like other inhibitors of HMG-CoA reductase, should not be used at an increased risk of rhabdomyolysis and renal insufficiency (against severe acute infection, arterial hypotension, trauma, planned large surgical operation, 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.

In patients with a reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome), when the level of cholesterol is raised, first therapy should be performed for the underlying disease.

Simvastatin is cautiously prescribed to people 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 simvastatin, therefore, one should avoid their simultaneous administration.

Simvastatin is not indicated in cases where there is hypertriglyceridemia 1, 4, and 5 types.

Treatment with simvastatin can cause myopathy, leading to rhabdomyolysis and kidney failure. The risk of this pathology increases in patients receiving one or more of the following medicines simultaneously with simvastatin: fibrates (gemfibrozil, fenofibrate), cyclosporine, nefazadone, macrolides (erythromycin, clarithromycin), antifungal agents from the azole group (ketoconazole, itraconazole) and inhibitors HIV protease (ritonavir). The risk of developing myopathy also increases in those with severe kidney failure.

Among the predisposing factors for the development of myopathy, there are elderly age (over 65 years), belonging to the female sex, uncontrolled hypothyroidism and renal insufficiency.

All patients starting therapy with Simvastatin, also 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 a malaise or fever.Therapy with the product must be stopped 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 Simvastatin, it is possible to increase the content of serum CK, which should be taken into account in differential diagnosis of chest pain. The criterion for the cancellation of the product is an increase in the content of CK in the serum 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 product 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 product must be taken as soon as possible.

If it's time to take the next dose, do not double the dose.

Patients with severe renal failure receive treatment under the control of kidney function.

The duration of the use of the product is determined individually by the attending physician.

The use of simvastatin is not recommended in women of childbearing age who do not use reliable methods of contraception.

Impact on the ability to drive vehicles and manage mechanisms

Care must be taken when driving vehicles and various mechanisms (risk of dizziness).

Drug Interactions

Pharmacodynamic interactions

Simultaneous use of simvastatin with fibrates, nicotinic acid in lipid-lowering doses (more than 1 g per day) increases the risk of myopathy, including rhabdomyolysis (with simultaneous use with fenofibrate, there is no evidence of increased risk, myopathy compared with monotherapy with each drug alone)

With the simultaneous use of Amlodipine with the drug Simvastatin in a dose of 80 mg, there is an insignificantly increased risk of myopathy.

Pharmacokinetic interactions

Inhibitors of the cytochrome isoenzyme CYP3A4 (itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors and nefazodone), involved in the metabolic conversion of simvastatin in the liver, increase the risk of myopathy and rhabdomyolysis during simvastatin therapy. Simultaneous use with these drugs is contraindicated.Caution should be given simultaneously with less potent inhibitors of the isoenzyme CYP3A4: cyclosporine, verapamil and diltiazem.

The daily dose of simvastatin when administered simultaneously with cyclosporine should not exceed 10 mg.

The daily dose of simvastatin against the simultaneous use of amiodarone or verapamil should not exceed 20 mg, and 40 mg should be combined with the simultaneous use of diltiazem, unless the expected benefit clearly exceeds the potential risk of myopathy and rhabdomyolysis.

Simvastatin 20-40 mg per day in healthy volunteers and patients with hypercholesterolemia potentiates the effects of indirect anticoagulants of coumarin derivatives (eg, warfarin), in particular, an increase in prothrombin time and the international normalized ratio (MHO). Therefore, in patients taking coumarin anticoagulants, prothrombin time and MHO should be determined before the start of simvastatin therapy, in the initial treatment period, with a change in the dose of simvastatin or drug withdrawal. When a stable prothrombin time and MHO are reached, further monitoring should be performed at intervals recommended for patients receiving anticoagulant therapy.Therapy with simvastatin does not cause changes in prothrombin time and the risk of bleeding in patients who do not take anticoagulants.

Kolestyramin and colestipol reduce bioavailability (the use of the drug simvastatin probably 4 hours after the application of these drugs, with an additive effect noted).

Simvastatin increases the concentration of Digoxin in the blood plasma.

Grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme and can increase the concentration in the blood plasma of substances metabolized with the CYP3A4 isoenzyme. The increase in the activity of HMG-KoA-reductase inhibitors after consuming 250 ml of juice per day is minimal and has no clinical significance. However, the consumption of a large amount of juice (more than 1 liter per day) with the use of simvastatin significantly increases the 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.

Analogues of the drug Simvastatin

Structural analogs for the active substance:

• Aktalipid;
• Atherostat;
• Vazilip;
• Vero Simvastatin;
• Zocor;
• Zokor forte;
• Zorstat;
• Ovenkor;
• Simvard;
• Simvakol;
• Simvale;
• Simvastatin Zentiva;
• Simvastatin Pfizer;
• Simvastatin Ferein;
• Simvastatin Chaykafarma;
• Simvastol;
• Symvor;
• Simgal;
• Simlo;
• Sinquard;
• Holvasim.

Analogues for the pharmacological group (statins):

• Akorta;
• Anistat;
• Apexstatin;
• Atherostat;
• Atokord;
• Atomax;
• Atorvastatin;
• Atorvox;
• Atoris;
• The Vasator;
• Vazilip;
• Zorstat;
• Cardiostatin;
• The Cross;
• Leskol;
• Leskol Fort;
• Lipobay;
• Lipon;
• Lipostat;
• Lipofford;
• Liprimar;
• Liptonorm;
• Lovacor;
• Lovastatin;
• Lovasterol;
• Mevakor;
• Medostatin;
• Mertenil;
• Ovenkor;
• Pravastatin;
• Rovacor;
• Rosuvastatin;
• Rosewood;
• Rosulip;
• Roxer;
• Tevastor;
• Torvazine;
• Torvacard;
• Tulip;
• Holvasim;
• Holletar.

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