Composition, form of production and packaging
The tablets covered with a film membrane of white or almost white color, round, slightly biconcave, with a facet.
1 tab.
simvastatin 10 mg
- "- 20 mg
Excipients: lactose monohydrate, pregelatinized starch, butyl hydroxy anisole, citric acid anhydrous, ascorbic acid, corn starch, microcrystalline cellulose, magnesium stearate.
Composition of the film shell: hypromellose, talc, propylene glycol, titanium dioxide.
7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
The tablets covered with a film membrane of white or almost white color, round, slightly biconcave, with a facet and with risk on one side.
1 tab.
simvastatin 40 mg
Excipients: lactose monohydrate, pregelatinized starch, butyl hydroxy anisole, citric acid anhydrous, ascorbic acid, corn starch, microcrystalline cellulose, magnesium stearate.
Composition of the film shell: hypromellose, talc, propylene glycol, titanium dioxide.
7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Lipid-lowering drug.
The active substance of the drug Vazilip В® is simvastatin, the main effect of which is a decrease in the total cholesterol (total Xc) and low-density lipoprotein (LDL-C) cholesterol in blood plasma. It is an inhibitor of HMG-CoA reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonic acid (early stage of Xc synthesis). Simvastatin reduces the concentration of total Xc, Xc-LDL and triglycerides (TG). The Xc content of very low density lipoproteins (Xc-VLDL) also decreases, while the high-density lipoprotein (Xc-HDL) cholesterol content moderately increases. Reduces the total content of cholesterol and LDL in cases of heterozygous family and non-family forms of cholesterolemia, with mixed hyperlipidemia, when elevated Xc content is a risk factor. The drug reduces the level of total Xc and Xc-LDL in patients with IHD, reducing the risk of myocardial infarction and death for these patients.
Simvastatin also significantly reduces the content of apolipoprotein B, moderately increases the concentration of Xc-HDL and reduces plasma concentrations of TG.As a result of these effects of simvastatin, the ratio of total Xc to total XC-HDL and Xc-LDL decreases to Xc-LBV.
Anti-atherosclerotic effect of simvastatin is a consequence of the drug on the walls of blood vessels and components. Simvastatin alters the metabolism of macrophages, inhibiting the activation of macrophages and the destruction of atherosclerotic plaques. The drug inhibits the synthesis of isoprenoids, which are growth factors in the proliferation of smooth muscle cells of the inner shell of vessels. The action of simvastatin improves the endothelium-dependent dilatation of blood vessels.
Therapeutic effect occurs after 2 weeks, the maximum effect is observed after 4-6 weeks of treatment.
PHARMACOKINETICS
Suction and distribution
Simvastatin is presented in an inactive lactone form, which is relatively well absorbed (from 61% to 85%) from the digestive tract. Bioavailability is less than 5%.After ingestion C max is achieved in 1-2 hours and decreases by 90% after 12 hours. Simultaneous food intake does not affect the absorption of the drug. With prolonged intake of cumulation of the drug in the body does not occur. Binding to blood plasma proteins - 98%.
Metabolism
Simvastatin is a substrate of CYP3A4. Metabolized in the liver, subjected to the effect of "first passage" through the liver (basically hydrolysed to its active form? -hydroxy acid).
Excretion
It is mainly excreted through the intestine (60%) in the form of metabolites. About 13% is excreted by the kidneys in an inactive form. T 1/2 is 1.9 hours.
INDICATIONS
Hypercholesterolemia
- Primary hypercholesterolemia or mixed dyslipidemia (in addition to diet and in the ineffectiveness of other non-pharmacological activities / physical activity and weight loss /);
- homozygous hereditary hypercholesterolemia (in addition to a special diet and lipid-lowering therapy (eg, LDL apheresis) or in the inefficiency of these measures).
Prevention of cardiovascular diseases
- Reduction of cardiovascular mortality and morbidity in patients with clinical manifestations of atherosclerotic cardiovascular diseases or diabetes mellitus, with normal or elevated cholesterol levels and as an additional measure to correct other risk factors and cardioprotective therapy.
DOSING MODE
Inside, once in the evening. The recommended dose of simvastatin varies from 5 mg to 80 mg once a day in the evening. Most often, the initial dose of the drug is 10 mg. Changes (selection) of the dose should be carried out at intervals of not less than 4 weeks. The maximum daily dose is 80 mg. The maximum daily dose is recommended only for patients with severe hypercholesterolemia or a high risk of cardiovascular complications. Duration of the drug is determined individually by the attending physician.
Hypercholesterolemia
The patient should follow a standard hypocholesterol diet throughout the entire period of treatment with Vasilip В® . The recommended initial dose of the drug for patients with hypercholesterolemia is 10 mg. With the aim of a more pronounced decrease in the level of X-LDL (more than 45%), treatment can be started from 20-40 mg / day (once in the evening).
In patients with homozygous hereditary hypercholesterolemia, the recommended daily dose of Vasilip В® is 40 mg 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); these patients are recommended to use Vasilip В® in combination with other lipid-lowering therapy (for example, apheresis of LDL).
Prevention of cardiovascular diseases
In patients with high risk of coronary heart disease, with or without hyperlipidemia, effective doses of the drug Vazilip В® 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 LDL content is less than 75 mg / dL (1.94 mmol / L), the total Xc content is less than 140 mg / dL (3.6 mmol / L), the dose of the drug should be reduced.
Concomitant therapy
The drug Vazilip В® is effective in monotherapy or in combination with bile acid sequestrants (for example, colestyramine and colestipol). In patients receiving cyclosporine, gemfibrozil, other fibrates or nicotinic acid (more than 1 g / day), the recommended initial dose of 5 mg, the maximum daily dose of the drug Vazilip В®is 10 mg. Further increase in dose in such situations is not recommended.
In patients who are simultaneously receiving amiodarone or verapamil, daily doses of the drug Vazilip В® should not exceed 20 mg.
In elderly patients and in patients with moderate renal insufficiency, dosage adjustment is not required.
In patients with severe renal failure (CC less than 30 ml / min), the recommended dose of Vasilip В® should not exceed 10 mg / day. If it is necessary to increase the dose, careful monitoring of such patients is necessary.
SIDE EFFECT
Classification of the incidence of adverse events (WHO): very often (> 1/10), often (> 1/100 to <1/10), infrequently (> 1/1000 to <1/100), rarely (> 1/10 000 to <1/1000), very rarely (from <1/10 000), including individual messages.
From the digestive system: rarely - constipation, abdominal pain, flatulence, dyspepsia, nausea, vomiting, diarrhea, pancreatitis, hepatitis, jaundice, increased activity of hepatic transaminases, alkaline phosphatase, KFK.
From the central and peripheral nervous system and sensory organs: rarely - headache, paresthesia, dizziness, peripheral neuropathy, asthenia, insomnia, convulsions, vagueness of vision, violation of taste sensations.
From the musculoskeletal system: rarely - myopathy, rhabdomyolysis, myalgia, muscle cramps.
Allergic and immunopathological reactions: developed syndrome of hypersensitivity (angioedema, lupus-like syndrome, rheumatic polymyalgia, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis, arthralgia, urticaria, photosensitivity, fever, flushing of the skin, dyspnea and severe weakness ).
Dermatological reactions: rarely - skin rash, skin itch, alopecia.
Other: rarely - anemia, palpitation, acute renal failure (due to rhabdomyolysis), decreased potency.
CONTRAINDICATIONS
- liver disease in the active phase or a persistent increase in the activity of hepatic transaminases of unclear etiology;
- simultaneous administration of inhibitors of the isoenzyme CYP3A4 (eg, itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone);
- Pregnancy;
- the period of lactation (breastfeeding);
- age under 18 years (effectiveness and safety of application not studied);
- Hypersensitivity to simvastatin and other components of the drug.
Caution should be given to the drug with alcohol abuse prior to initiation of therapy, liver diseases in history, severe electrolyte imbalance, severe endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), myopathy, uncontrolled epilepsy, extensive surgical interventions, trauma, deficiency lactase, galactosemia, or glucose-galactose malabsorption syndrome (because the drug contains lactose), concomitant administration with gemfibrosin, cyclosporine, nicotine (more than 1 g / day), amiodarone, verapamil, diltiazem, fenofibrate, grapefruit juice.
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy. There was no evidence of an increase in the incidence of congenital malformations in children of women taking simvastatin or another HMG-CoA reductase inhibitor. When a pregnant woman receives simvastatin, a decrease in the fetal levels of mevalonate, which is a precursor of the biosynthesis of Xs, is possible. The abolition of hypolipidemic drugs during pregnancy does not have a significant effect on the results of the short-term risk associated with primary hypercholesterolemia.
Simvastatin should not be used in pregnant women, in women planning pregnancy, or with suspected pregnancy. If during pregnancy pregnancy occurs, the drug should be canceled, and the woman is warned about possible danger to the fetus.
During the treatment with Vasilip В® , women of reproductive age should use reliable contraceptives.
It is not known whether the drug is excreted into breast milk, so therapy with Vasilip В® during breastfeeding is contraindicated.
APPLICATION FOR FUNCTIONS OF THE LIVER
With renal failure of mild or moderate severity, correction of the dosing regimen is not required. For renal insufficiency of severe degree (QC less than 30 ml / min) or with simultaneous application of fibrates, nicotinamide, the recommended dose of Vasilip should not exceed 10 mg / day. If necessary, an increase in the dose in this category of patients should be carried out under careful medical supervision.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in acute and exacerbation of chronic liver diseases, as well as with a persistent increase in the activity of transaminases of unknown origin.
APPLICATION FOR CHILDREN
Contraindication: age under 18 years (efficacy and safety of use not studied).
APPLICATION IN ELDERLY PATIENTS
In elderly patients, dosage adjustment is not required.
SPECIAL INSTRUCTIONS
In patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) with an increase in Xc level, the underlying underlying disease should first be treated.
Patients with severe renal failure are treated with renal function.
Treatment with simvastatin, as with other inhibitors of GMC-CoA reductase, can cause myopathy, sometimes resulting in rhabdomyolysis with or without renal failure, due to myoglobinuria. The risk of myopathy increases with an increase in the dose of simvastatin and in patients with severe renal insufficiency. In the treatment with simvastatin, it is possible to increase the content of serum CK, which should be taken into account in the differential diagnosis of chest pain and after intensive physical exertion.
Before starting therapy with VasilipВ® or increasing its dose, patients should be informed of the risk of developing myopathy and the need to consult a doctor immediately if there is unexplained pain, tension or weakness in the muscles, especially if accompanied by malaise or fever. The baseline level of CKD should be determined before the start of therapy in the following situations:
- in elderly patients;
- with kidney damage;
- with decompensated hypothyroidism;
- with an aggravated family history of hereditary muscle diseases;
- if there is a history of toxic effects on the muscles of statins or fibrates;
- with alcohol abuse.
It is necessary to evaluate the possible risk and the expected benefit and during the clinical monitoring recommended on the background of therapy. If initially the level of CK is significantly increased (more than 5 times with respect to IGN), the measurement should be repeated after 5-7 days to confirm the results. With a significant initial increase in the level of CK (more than 5 times relative to IGN), the drug should not be prescribed.
Before and during the course of treatment, the patient should be on a hypocholesterol diet.
During treatment with Vasilip В®, when muscle pain, weakness, or seizures appear, it is necessary to determine the level of CK. The criterion for the discontinuation of the drug is an increase in the serum levels of CK in more than 5 times relative to IGN. If the muscle symptoms are severe and cause discomfort, even if the CK level is less than 5 times the VGN, it may be necessary to stop treatment. If suspected of myopathy, therapy should be discontinued, regardless of the cause of myopathy.
If the symptoms disappear and the content of CPK returns to normal, reintroduction of a statin or an alternative drug of the same class in a minimal clinically effective dose and under careful medical supervision is possible. Therapy with Vasilip В® should be temporarily stopped a few days before major surgical interventions.
Patients with severe renal failure are treated with renal function.
Measures to reduce the risk of myopathy caused by drug interactions
The risk of myopathy and rhabdomyolysis increases significantly with simultaneous use of simvastatin and potent inhibitors of CYP3A4 (eg, itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone), gemfibrozil or cyclosporine. The risk of myopathy and rhabdomyolysis also increases with the combined use of fibrates and high doses of nicotinic acid (more than 1 g / day) or with simultaneous therapy with amiodarone or verapamil with high doses of simvastatin. The risk also increases somewhat with the simultaneous administration of diltiazem and high doses of simvastatin (80 mg). Therefore, the use of simvastatin concomitantly with itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors and nefazodone is contraindicated. If you can not refuse therapy with the listed inhibitors of CYP3A4, you should refrain from prescribing simvastatin. Simvastatin should also be combined with caution with some other, less potent inhibitors of CYP3A4: cyclosporine, verapamil and diltiazem.
Simultaneous administration of simvastatin and grapefruit juice should be avoided.
In patients taking ciclosporin, gemfibrozil or high doses of nicotinic acid (more than 1 g / day), the daily dose of simvastatin should not exceed 10 mg.
Simultaneous appointment of simvastatin and gemfibrozil is possible only in those cases when the expected benefit significantly exceeds the potential risk of such a drug combination. The benefits of combined use of simvastatin 10 mg / day and other fibrates (other than fenofibrate), nicotinic acid (more than 1 g / day) or cyclosporine should be carefully weighed against the potential risk of such combinations.
There is a risk of myopathy in the appointment of fenofibrate and simvastatin alone, so caution is needed when taking this combination at the same time.
When taking simvastatin at doses exceeding 20 mg / day, simultaneous administration of amiodarone or verapamil should be avoided, unless the expected benefit exceeds the potential risk of myopathy.
Effects on the liver
Treatment with simvastatin may cause an increase in the activity of hepatic enzymes in the serum. This increase is usually insignificant and clinically insignificant.After the drug is discontinued, transaminase levels usually slowly decrease to the baseline level. Nevertheless, before the treatment begins, it is necessary to conduct a study of liver function in the future (to monitor the activity of hepatic transaminases every 6 weeks for the first 3 months, then every 8 weeks for the remaining first year, and then once every six months). If necessary, higher doses up to 80 mg, liver function monitoring is required before increasing the dose in 3 months after the increase, and then periodically (e.g., once every 1 to 6 months) in the first year of treatment. When ACT persistent increase the activity and / or serum ALT 3 times the ULN, simvastatin treatment should be discontinued.
Be wary appoint persons who abuse alcohol and / or have a history of liver disease.
Impact on the ability to drive vehicles and manage mechanisms
On the adverse effects of the drug Vasilip В® driving ability and work with the mechanisms have not been reported. However, it should be noted that in the post-marketing use of simvastatin observed isolated cases of vertigo.
OVERDOSE
There is evidence of several cases of overdosage with simvastatin. The maximum dose taken was 3.6 g
Treatment: In case of overdose symptomatic treatment; necessary to carry out common activities: monitoring and maintenance of vital functions, preventing further absorption drugs (gastric lavage, activated charcoal or laxatives). It is recommended to monitor liver function and CK. There is no specific antidote.
With the development of myopathy with rhabdomyolysis (a rare, but serious side effects), stop taking the drug, the patient enter a diuretic and sodium hydrogen carbonate (w / infusion). Rhabdomyolysis can cause hyperkalemia, which can be eliminated in / from the introduction of calcium chloride and calcium gluconate, glucose infusion with insulin, using potassium ion exchangers or, in severe cases, by dialysis.
DRUG INTERACTION
Pharmacodynamic interactions
Concomitant use of simvastatin with fibrates, nicotinic acid (more than 1 g / d) increases the risk of myopathy, including rhabdomyolysis (while the use of fenofibrate - not shown increased risk of myopathy, compared to a monotherapy each drug alone).
The simultaneous use of gemfibrozil may lead to an increase in the concentration of simvastatin in serum.
pharmacokinetic interactions
Inhibitors of cytochrome 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 on background therapy with simvastatin. The simultaneous use of these drugs is contraindicated.
Precautions must be simultaneously administered with less potent inhibitors of CYP3A4: cyclosporine, verapamil and diltiazem. The daily dose of simvastatin while receiving cyclosporine should not exceed 10 mg. The daily dose of simvastatin on the background of the simultaneous reception of amiodarone or verapamil should not exceed 20 mg, and 40 mg - against the backdrop of the simultaneous reception of diltiazem, unless the expected benefit clearly outweighs the potential risk of myopathy and rhabdomyolysis.
Simvastatin 20-40 mg / day volunteers and patients with hypercholesterolemia potentiates the effects of coumarin anticoagulant (e.g., warfarin), in particular an increase in prothrombin time, MHO. Therefore, in patients taking coumarin anticoagulants, prothrombin time and MHO should be determined before starting therapy with simvastatin, in the initial period of treatment, when changing the dose of simvastatin or eliminate drug. Upon reaching stable indicator prothrombin time and MHO, further control should be carried out at intervals recommended for patients receiving anticoagulant therapy. Therapy with simvastatin did not cause changes in prothrombin time and bleeding risk in patients not taking anticoagulants.
Grapefruit juice inhibits the CYP3A4 activity. Simultaneous reception of a large amount of grapefruit juice (more than 1 liter per day) and simvastatin leads to a significant increase in the concentration in the blood plasma simvastatinovoy acid. Therefore, during treatment with simvastatin should avoid grapefruit juice.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be kept out of reach of children at a temperature not higher than 30 В° C. Shelf life - 3 years.
