VAZILIP
Active material: Simvastatin
When ATH: C10AA01
CCF: Lipid-lowering drugs
ICD-10 codes (testimony): E78.0, E78.2, G45, i20, I21, I25.1, I61, I63
When CSF: 01.12.11.03
Manufacturer: KRKA d.d. (Slovenia)
Pharmaceutical form, composition and packaging
Pills, Film-coated white or nearly white, round, slightly biconcave, chamfered.
| 1 tab. | |
| simvastatin | 10 mg |
| -“- | 20 mg |
Excipients: lactose monohydrate, pregelatinized starch, ʙutilgidroksianizol, lemon acid (Anhydrous), vitamin C, corn starch, microcrystalline cellulose, magnesium stearate, hydroxypropyl, talc, Titanium dioxide.
The composition of the coating film: gipromelloza, talc, propylene glycol, Titanium dioxide.
7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.
Pills, Film-coated white or nearly white, round, slightly biconcave, with chamfer and scored on one side.
| 1 tab. | |
| simvastatin | 40 mg |
Excipients: lactose monohydrate, pregelatinized starch, ʙutilgidroksianizol, lemon acid (Anhydrous), vitamin C, corn starch, microcrystalline cellulose, magnesium stearate.
The composition of the coating film: gipromelloza, talc, propylene glycol, Titanium dioxide.
7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.
Pharmacological action
Lipid-lowering drugs.
The active substance of the preparation Vazilip® is simvastatin, the main effect of which is the reduction of total cholesterol (total Xc) and low density lipoprotein cholesterol (LDL-C) plasma. Is an inhibitor of HMG-CoA reductase inhibitors, enzyme, catalyzes the conversion of HMG-CoA to mevalonic acid (early stage of synthesis of Xc). Simvastatin lowers the concentration of total Cholesterol, LDL-C and triglycerides (TG). The content of very low density lipoprotein Cholesterol (Hs-LPONP) It also reduces the, While the contents of high density lipoprotein Cholesterol (Hs-HDL) moderate increases. Reduces the total Cholesterol and LDL CHOLESTEROL in cases of heterozygous familial and precluded from accompanying forms holesterinemii, When mixed Hyperlipidemia, When elevated levels of Cholesterol is a risk factor. The drug lowers total Cholesterol and LDL-Cholesterol in patients with ischemic heart disease, reducing the risk of myocardial infarction and death for these patients.
Simvastatin also significantly reduces apolipoprotein in, moderately increases the concentration of Cholesterol-HDL and reduces plasma concentration of TG. As a result of these effects, simvastatin reduced the ratio of total Cholesterol to a common XC-HDL and LDL to XC-XC-LPVN.
Antiaterosklerotičeskij simvastatin effect is a consequence of the impact of the drug on the walls of blood vessels and blood components. Simvastatin alters metabolism of macrophages, oppressing the activation of macrophages and the destruction of atherosclerotic plaques. The drug suppresses the synthesis of isoprenoids, are growth factors in the proliferation of smooth muscle cells of the inner lining of blood vessels. Under the influence of simvastatin improves endothelium-dependent vasodilation.
Therapeutic effect occurs through 2 of the week, maximum effect is observed after 4-6 weeks of treatment.
Pharmacokinetics
Absorption and distribution
Simvastatin is presented in an inactive form laktonnoj, that is relatively well absorbed (from 61% to 85%) from the gastrointestinal tract. Bioavailability – less 5%. After oral administration, Cmax achieved through 1-2 h and is reduced by 90% through 12 no. Simultaneous eating does not affect the absorption of the drug. In the long admission cumulation of drug in the body does not occur. The binding to plasma proteins – 98%.
Metabolism
Simvastatin is a CYP3A4 substrate. It is metabolized in the liver, exposed effect “first pass” through the liver (mainly hydrolyses in its active form β-gidrokshikislotu).
Deduction
Mostly displayed through the intestines (60%) as metabolites. About 13% report the news in the inactive form. T1/2 is 1.9 no.
Testimony
Hypercholesterolemia
-primary hypercholesterolemia or Mixed Dyslipidemia (In addition to the diet and the ineffectiveness of other non-drug interventions/physical activity and decrease in body weight/);
-homozygous hypercholesterolemia is hereditary (In addition to a special diet and cholesterol-lowering treatment/for example, LDL aferezu/or the ineffectiveness of these measures).
Prevention of cardiovascular diseases
— reduction of cardiovascular mortality and morbidity in patients with symptomatic atherosclerotic cardiovascular disease or diabetes, with normal or elevated cholesterol level and as a complementary measure to the correction of other risk factors and kardioprotektornoj therapy.
Dosage regimen
Inside, Once in the evening. The recommended dose of simvastatin varies from 5 mg 80 mg 1 time / day in the evening. Most often the initial dose of the drug – 10 mg. Changes (selection) the dose should be carried out at intervals of not less than 4 weeks. The maximum daily dose – 80 mg. The maximum daily dose is recommended only for patients with severe hypercholesterolemia, or high risk of cardiovascular complications. Duration of use of the drug is determined by the attending physician individually.
Hypercholesterolemia
The patient must comply with the standard gipoholesterinovu diet throughout the period of treatment with Vazilip®. The recommended initial dose of the drug for patients with hypercholesterolemia, is 10 mg. With a view to more pronounced decrease the level of Cholesterol-LDL (more than 45%), treatment can be started with the 20-40 mg / day (Once in the evening).
In patients with homozygous hypercholesterolemia is hereditary the recommended daily dose of the drug Vazilip® is 40 mg in the evening or 80 mg 3 admission (20 mg in the morning, 20 mg and day 40 mg in the evening); these patients Vazilip® recommended for use in combination with another cholesterol-lowering therapy (eg, aferezom ENGINEERS).
Prevention of cardiovascular diseases
In patients with a high risk of CORONARY HEART DISEASE, with or without hyperlipidaemia effective dosage Vazilip® up 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 of the week, if necessary, the dose can be increased to 40 mg / day. If the content of LDL is less 75 mg / dL (1.94 mmol / l), the content of total Cholesterol less than 140 mg / dL (3.6 mmol / l), drug dose should be reduced.
Soputstvuyushtaya therapy
Product Vazilip® effective alone or in combination with bile acid sekvestrantami (eg, cholestyramine and colestipol). Patients, receiving therapy ziklosporinom, gemfibrozilom, other fibratami or Nicotinic Acid (more 1 g / day), The recommended starting dose 5 mg, the maximum daily dose of the drug Vazilip® is 10 mg. Further increase the dose in such situations is not recommended.
Patients, at the same time receiving amiodarone or Verapamil, daily dose of the drug Vazilip® should not exceed 20 mg.
In elderly patients and patients with moderately expressed renal insufficiency changes do not require doses.
In patients with renal insufficiency (CC less than 30 ml / min) the recommended dose of the drug Vazilip® should not exceed 10 mg / day. If necessary, increase the dose, careful monitoring of such patients.
Side effect
Classification of the incidence of side effects (WHO): Often (> 1 /10), often (from > 1/100 to < 1/10), infrequently (from > 1/1000 to < 1 /100), rarely (from >1/10 000 to < 1/1000), rarely (from < 1/10 000), including isolated reports.
From the digestive system: rarely – constipation, abdominal pain, flatulence, dyspepsia, nausea, vomiting, diarrhea, pancreatitis, hepatitis, jaundice, increase in liver transaminases, Alkaline phosphatase, CPK.
Central and peripheral nervous system and sensory organs: rarely – headache, paresthesia, dizziness, perifericheskaya neuropathy, asthenia, insomnia, convulsions, blurred vision, dysgeusia.
On the part of the musculoskeletal system: rarely – myopathy, raʙdomioliz, myalgia, muscle cramps.
Allergic and immunopathological reactions: expanded hypersensitivity syndrome (angioedema, lupus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, thrombocytopenia, eozinofilija, increased erythrocyte sedimentation rate, arthritis, arthralgia, hives, photosensitivity, fever, rush of blood to the face, shortness of breath and severe weakness).
Dermatological reactions: rarely – skin rash, itching, alopecia.
Other: rarely – anemia, heartbeat, acute renal failure (due to rhabdomyolysis), reduced potency.
Contraindications
-liver disease in active phase or persistent increase in liver transaminaz unclear etiology;
-simultaneous inhibitors izofermenta CYP3A4 (eg, itraconazole, ketoconazole, HIV protease inhibitors, Erythromycin, clarithromycin, telithromycin and nefazodone);
- Pregnancy;
- Lactation (breast-feeding);
- Up to 18 years (efficacy and safety have not been studied);
-hypersensitivity to simwastatino and other components of the drug.
FROM caution should designate product if alcohol abuse before the start of therapy, a history of liver disease, heavy violations elektrolitnogo balance, pronounced endocrine and metabolic irregularities, hypotension, severe acute infections (sepsis), myopathies, uncontrolled epilepsy, extensive surgery, injuries, lactase deficiency, Galactose or glucose-Galactose malabsorption syndrome (tk. the drug contains lactose), together with the admission gemfibrozinom, cyclosporine, nicotinic acid (more 1 g / day), amiodarone, verapamil, diltiazemom, fenofibratom, grapefruit juice.
Pregnancy and lactation
The drug is contraindicated in pregnancy. It has not been proved to increase the frequency of birth defects in children of women, taking simvastatin or another inhibitor of HMG-CoA reductase inhibitors. When hiring a pregnant woman simvastatin may reduce fetal levels of mevalonate, which is the precursor of the biosynthesis of Chs. Cancellation of lipid means pregnancy does not significantly affect the results of short-term risk, associated with primary hypercholesterolemia.
Simvastatin should not be used in pregnant women, female, planning pregnancy, or suspected pregnancy. If pregnancy was achieved during treatment, the drug must be cancelled, and the woman warned of the possible danger to the fetus.
During drug treatment Vazilip®, women of reproductive age must use reliable methods of contraception.
Unknown, whether the drug is excreted in breast milk, Therefore, drug therapy Vazilip® breastfeeding is contraindicated.
Cautions
In patients with reduced function of thyroid gland (gipotireoz) or if you have some kidney diseases (nephrotic syndrome) Chs level should first carry out therapy of the underlying disease.
Patients with severe renal failure treatment are under the control of the kidney.
Treatment simvastatinom, like other inhibitors of MMC-CoA reductase, can cause myopathy, sometimes resulting in rabdomiolizu with or without the development of renal failure, in consequence of the mioglobinurii. The risk of myopathy is increased with increasing doses of simvastatin and in patients with severe renal insufficiency. When treating simvastatinom may increase the content of serum CPK, that should be taken into account in the differential diagnosis of pain behind the breastbone and following intense physical activity.
Before starting therapy with Vazilip® or an increase in dose, patients should be informed about the risk of MYO and the need to immediately contact a physician in case of unexplained pain, strain or muscle weakness, especially if it's accompanied by malaise or fever. The initial level of CPK before therapy must be defined in the following situations:
-older patients;
— defeat of kidneys;
— декомпенсированном hypothyroidism;
— If a family history of hereditary muscle diseases;
— If you have a history of toxic effects on the muscles of statin or fibrate;
— alcohol abuse.
It is necessary to assess the potential risks and expected benefits and during therapy to clinical therapy monitoring. If the initial level of CPK significantly increased (more 5 times concerning the VGN), the measurement must be repeated after 5-7 days to certify the results. With a substantial source of increase of level of CPK (more 5 times concerning the VGN) the drug is not recommended to appoint.
Before and during the course of treatment the patient should be on gipoholesterinovoj diet.
During drug treatment Vazilip® When you see the muscle pain, weakness or cramps, you must determine the level of CPK. Criterion of the drug provides increase of CPK in the blood serum of more than 5 times concerning the VGN. If muscular symptoms and cause pronounced discomfort, even if CPK is less 5 times concerning the VGN, perhaps, treatment should be stopped. If myopathy is suspected, therapy should be stopped, regardless of the cause myopathy.
If the symptoms disappear, and content of the CKF has returned to a normal level, possible renomination statina or alternative drug of the same class in the minimum clinically effective dose and under careful medical supervision. Vazilip therapy® you need to temporarily stop a few days before the major surgical interventions.
Patients with severe renal failure treatment are under the control of the kidney.
Measures to reduce the risk of myopathy, caused by drug interactions
The risk of myopathy and rhabdomyolysis is greatly increased, while the use of simvastatin and strong CYP3A4 inhibitors (eg, itraconazole, ketoconazole, Erythromycin, clarithromycin, telitromicina, HIV protease inhibitors, nefazodona), gemfibrosila or Cyclosporine. The risk of myopathy and rhabdomyolysis is also increased when sharing fibrate and high doses of Nicotinic Acid (more 1 g / day) or if simultaneous therapy amiodarone or Verapamil with high doses of simvastatin. The risk also increases slightly while appointing high doses of simvastatin and diltiazem (80 mg). Hence, application of simvastatin simultaneously with itrakonazolom, ketoconazole, Erythromycin, clarithromycin, telitromicinom, HIV protease inhibitors and nefazodonom counter. If you cannot abandon the therapies listed CYP3A4 inhibitors, should desist from the appointment of simvastatin. Simvastatin also need to be wary combine with certain other, less strong CYP3A4 inhibitors: cyclosporine, Verapamil and diltiazem.
Avoid the simultaneous reception of simvastatin and grapefruit juice.
Patients, receiving ciclosporin, gemfibrozil or high doses of Nicotinic Acid (more 1 g / day), daily dose of simvastatin should not exceed 10 mg.
The simultaneous appointment of simvastatin and gemfibrosila is possible only in cases, when expected benefit significantly outweighs the potential risk of this drug combination. The benefits of the combined use of simvastatin 10 mg/day and other fibrate (In addition to fenofibrata), nicotinic acid (more 1 g / day) or Cyclosporine should be carefully weighed against the potential risk of such combinations.
There is a risk of myopathy when assigning separately fenofibrata and simvastatin, Therefore there is a need for caution while receiving this combination.
When taking simvastatin in doses, exceeding 20 mg / day, You must avoid the simultaneous appointment of amiodarone or Verapamil, except, when expected benefit exceeds the potential risk of myopathy.
Effect on liver
Simvastatinom treatment can cause increase in liver enzymes in the serum. This enhancement is usually clinically insignificant and inconsequential. After the drug transaminaz levels usually decrease slowly to baseline. Nonetheless, before the start of treatment and thereafter, it is necessary to conduct a study of the liver (monitor activity transaminaz liver every 6 weeks within the first 3 months, then every 8 weeks for the remainder of the first year, and then 1 semi-annually). If necessary, increase the dose to 80 mg, required monitoring of the liver before increasing the dose, through 3 months after the increase and then periodically (eg, 1 once every 6 Months) during the first year of treatment. The steady increase in activity ACT and/or ALT in serum in 3 raza about VGN, simvastatinom treatment should be discontinued.
Be wary appoint persons, alcohol abusers, and/or have a history of liver disease.
Effects on ability to drive vehicles and management mechanisms
The adverse effect of drug Vazilip® on the ability to drive and work with mechanisms not reported. Nonetheless, should be considered, What if postmarketingovom use of simvastatin noted isolated cases of Vertigo.
Overdose
There are several cases of overdose simvastatin. The maximum dose is adopted 3.6 g.
Treatment: in the case of an overdose of symptomatic treatment; It is necessary to carry out general activities: monitoring and maintenance of the vital functions, to prevent the further intake of medication (gastric lavage, administration of activated charcoal or laxatives). It is recommended that monitoring of liver function and the CKF. There is no specific antidote.
With the development of MYO with rhabdomyolysis is (rare, but severe side effects) You should immediately discontinue use of the drug, enter patient diuretic and sodium bicarbonate (in / in infusion). Rhabdomyolysis can cause giperkaliemia, that can be addressed in/with the introduction of calcium chloride and calcium gluconate, infusion of glucose with insulin, use of potassium ion or, in severe cases, using hemodialysis.
Drug Interactions
Pharmacodynamic interactions
The simultaneous use of simvastatin with fibratami, nicotinic acid (more 1 g / day) increases the risk of myopathy, including rhabdomyolysis (together with the application fenofibratom – It has not been proved to increase the risk of Myopathy in comparison with each drug alone in isolation).
The simultaneous use of gemfibrozilom can lead to increased concentrations of simvastatin in serum.
Pharmacokinetic interactions
Inhibitors zitohroma CYP3A4 (itraconazole, ketoconazole, Erythromycin, clarithromycin, telithromycin, HIV protease inhibitors and nefazodone), involved in metabolic transformation of simvastatin in the liver, increase the risk of myopathy and rhabdomyolysis while therapy simvastatinom. The simultaneous use of these drugs is contraindicated.
The caution should be appointed with less potent inhibitors of CYP3A4: cyclosporine, Verapamil and diltiazem. Daily dose of simvastatin together with ziklosporinom shall not exceed 10 mg. Daily dose of simvastatin on simultaneous reception background amiodarone or Verapamil should not exceed 20 mg, and 40 mg – amid simultaneous reception diltiazema, unless the expected benefit clearly does not exceed the potential risk of myopathy and rhabdomyolysis.
Simwastatin dose 20-40 mg/day for volunteers and patients with hypercholesterolemia potenziruet effects kumarinovykh anticoagulants (eg, warfarin), in particular an increase in prothrombin time, MHO. Therefore patients, receiving coumarin anticoagulants, Prothrombin time and MHO should be determined before therapy simvastatinom, in the initial period of treatment, When you change the dose or eliminate the medication simvastatin. When it reaches a stable measure prothrombin time and MPE, further control should be spacing, recommended for patients, receiving anticoagulant therapy. Simvastatinom therapy does not cause changes in prothrombin time and the risk of bleeding in patients, do not take anticoagulants.
Grapefruit juice inhibits CYP3A4 activity. Simultaneous intake of large quantities of grapefruit juice (more 1 liters per day) and simvastatin leads to a significant increase in plasma concentrations of simvastatinovoj acid. Therefore, During simvastatinom therapy should avoid eating grapefruit juice.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 3 year.
