Simvalimit

General characteristics. Structure:

Active ingredient: 10 mg or 20 mg of a simvastatin.

Excipients: lactoses monohydrate, starch corn, cellulose microcrystallic, methyl cellulose, magnesium stearate, butylhydroxyanisole, ascorbic acid, citric acid monohydrate.

White film cover: 33G28707 Opadray white (gipromelloza of 40%, lactoses monohydrate, macrogoal 3000, titanium dioxide (E171), triacetin, karnaubsky wax.

Light pink film cover: 85F 24678 Opadray pink (polyvinyl alcohol the dioxide (E171), a macrogoal 3000, talc, ferrous oxide which is partially hydrolyzed 40%, titanium black (E172), ferrous oxide yellow (E172), кармоизин (azoruby) (E122), karnaubsky wax.

Pharmacological properties:

Pharmacodynamics. Симвалимит® (симвастатин) – the medicine regulating the level of lipids. It concerns group of редуктазы3-гидрокси-3-метилглутарил-коэнзима A inhibitors (inhibitors of GMG-KOA reductase) which call also statines. As a result of blockade of GMG-KOA reductase transformation GMG-KOA into mevalonovy acid, being the predecessor of cholesterol is slowed down, and, thus, the amount of cholesterol in cells decreases.

As synthesis of cholesterol proceeds, generally in a liver, the scene of action of statines is the hepatocyte. Statines reduce concentration of the general cholesterol, cholesterol of lipoproteins of low (LPNP) and very low density (LPONP) in plasma. They are also capable to lower the level of triglycerides and to increase the level of cholesterol of lipoproteins of the high density (LPVP). However hypolipidemic effect of drugs of this group is explained by one more mechanism. At decrease in intracellular reserves of cholesterol in a membrane of hepatocytes the number of receptors of LPNP kompensatorno increases that promotes removal of LPNP of an izkrova.

Pharmacokinetics. Simvastatin is soaked up in digestive tract and after hydrolysis turns into an active form in the form of beta hydroxyacid. Both other active and inactive metabolites are allocated. The maximum concentration of drug in a blood plasma is reached during 1,3-2,4 h.

Intensive metabolism of the first passing through a liver – the place of the main effect of the medicine is characteristic of a simvastatin. Less than 5% of the dose accepted inside come to a blood stream in the form of active metabolites. Linkng with proteins of a blood plasma both the simvastatin, and its active metabolite (in the form of beta hydroxyacid) reaches 95 %.

Out of an organism симвастатин it is brought, generally with excrements, coming to digestive tract with bile in the form of metabolites. About 10-15 % of the accepted quantity are removed with urine, mainly, in the form of inactive metabolites.

Indications to use:

- primary hypercholesterolemia

- hereditary heterozygous hypercholesterolemia

- an inborn homozygous hypercholesterolemia or the combined lipidemia which does not give in to correction by means of a diet and other relevant activities

- for decrease in risk of coronary incidents at patients with atherosclerosis, owing to a hypercholesterolemia

- for delay of progressing of coronary atherosclerosis at patients with coronary heart disease at whom the level of the general cholesterol is equal to 5,5 mmol/l or above.

Route of administration and doses:

Before an initiation of treatment of Simvalimitom® patients should recommend a usual diet with the low content of cholesterol which should adhere during the entire period of treatment.

Primary hypercholesterolemia, hereditary heterozygous hypercholesterolemia, the combined lipidemia. The recommended initial dose makes 10 mg once a day, in the evening. The maximum daily dose – 80 mg. The dose is selected at an interval of 4 weeks. The chosen dose is accepted in one step, in the evening.

Inborn homozygous hypercholesterolemia. Apply 40 mg once in the evening or on 80 mg a day, having divided this dose into three receptions (the greatest dose is accepted in the evening).

Decrease in risk of coronary incidents of upatsiyent with atherosclerosis, delay of progressing of coronary atherosclerosis at patients with coronary heart disease. An initial dose – 20 mg once a day, in the evening. Further the dose is selected at least once in 4 weeks. The maximum daily dose – 80 mg once.

At the combined use of Simvalimita® with cyclosporine, fibrata or the niacin used as hypolipidemic means, the recommended maximum daily dose of drug – 10 mg. To patients with a renal failure of easy or average degree to select a dose there is no need. However, in case of a heavy renal failure (clearance of creatinine less than 30 mg/min.) the recommended initial dose makes 5 mg a day, patients of this category need careful observation.

Features of use:

Juice of grapefruit increases concentration симвастатинав to a blood plasma.

Grapefruit juice inhibits activity of P450 3A4 cytochrome, in large numbers, like other inhibitors of P450 3A4 cytochrome, increases Cmax and AUC of a simvastatin (beta hydroxyacid) and risk of a myopathy.

It must be kept in mind that during treatment of Simvalimitom® activity of serumal aminotransferases can exceed limits of norm. These raised indicators usually without interruption in treatment decrease to the level observed before an initiation of treatment. Functional indicators of a liver (activity of "hepatic" transaminases) should be defined before an initiation of treatment, then – in 1-3 months after an initiation of treatment, and further – each 6 months. If during treatment find increase in activity of serumal transaminases, carry out repeated hepatic tests. However, if activity of ALT and nuclear heating plant exceeds the upper bound of norm by 3 times and more for a long time, treatment should be stopped. Симвалимит® the patients having diseases of a liver and alcoholism should apply with care.

With care apply Simvalimit® at arterial hypotension, a heavy renal failure, at epilepsy, extensive surgical interventions, injuries, states after organ transplantation against the background of immunodepressive therapy.

Before the beginning and during treatment it is necessary to define activity of a kreatinfosfokinaza. If at the patient this indicator is raised, or muscular pains, morbidity or weakness of muscles are observed, it is necessary to estimate probability of development of a myopathy. Patients need to recommend to report about muscular pains of not clear origin, morbidity or weakness of the muscles which are especially accompanied with the general weakness and fever. Treatment should be stopped if activity of a kreatinfosfokinaza by 10 times exceeds the upper bound of norm, there is a suspicion on development of a myopathy, or it is diagnosed. It is necessary to estimate carefully risk of development of a rabdomioliz and a secondary renal failure at patients with heavy acute infections, hypotension, injuries or undergone a heavy operation, with endocrine diseases, disturbances of metabolism and electrolytic balance, and also in case of uncontrollable spasms.

Prior to treatment and in its initial stage it is recommended to conduct ophthalmologic examination (biomicroscopy of eyes).

During treatment it is regularly necessary to determine cholesterol level in a blood plasma.

At patients with a hereditary homozygous hypercholesterolemia who completely have no receptors of LPNP Simvalimit® is less effective.

Patients with a lactose intolerance should mean that 1 tablet from 10 mg of Simvalimita® contains 55,95mg, and from 20 mg of Simvalimita® – 111,90 mg of lactose.

Pregnancy and lactation. Use of statines is contraindicated at pregnancy and breastfeeding. At treatment by statines women of reproductive age during treatment and within 1 month after its termination should apply the corresponding contraceptives. If during treatment pregnancy nevertheless occurs, it is necessary to stop use of a medicine.

Симвалимит® does not exert impact on ability to manage the vehicle and to service potentially dangerous mechanisms.

Side effects:

- nausea, vomiting, a gastralgia, abdominal pains, a lock or diarrhea, a meteorism, hepatitis, jaundice, perhaps expressed and steady increase in activity of "hepatic" transaminases, an alkaline phosphatase and kreatinfosfokinaza, acute pancreatitis;

- asthenic syndrome, dizziness, headache, sleeplessness, spasms, paresthesias, peripheral neuropathy, sight vagueness, disturbance of flavoring feelings;

- myopathy, mialgiya, muscular weakness, рабдомиолиз;

- a Quincke's disease, a volchanochnopodobny syndrome, a rheumatic polimialgiya, a dermatomyositis, a vasculitis, arthritis, an arthralgia, a small tortoiseshell, an alopecia, a photosensitization, fever, skin rash, an itch, a dermahemia, "inflows" of blood to the person;

- anemia, thrombocytopenia, eosinophilia, increase in SOE; 

- heartbeat, asthma;

- an acute renal failure (owing to a rabdomioliz);

- decrease in a potentiality.

Interaction with other medicines:

Antibiotics кларитромицин and erythromycin, antidepressant нефазодон, antifungal means итраконазол and ketokonazol, perhaps, other derivatives of an imidazole and triazole, anti-virus means (inhibitors of virus proteases), an immunosuppressant cyclosporine, and also the means lowering the level of lipids – fibrata and niacin, can increase risk of development of a myopathy.

Simultaneous use of statines and anticoagulants – oxycoumarin derivatives (for example, an atsenokumarola, warfarin) can increase a prothrombin time and risk of bleeding.

Contraindications:

- hypersensitivity to drug components;

- acute disease of a liver or long increase in activity of serumal aminotransferases of not clear etiology;

- porphyria;

- beremennost lactation period;

- children's and teenage age up to 18 years;

- diseases of skeletal muscles;

- deficit of lactase, lactose intolerance, syndrome of glyukozo-kalaktozny malabsorption.

Overdose:

There are messages only on several cases of overdose which proceeded asymptomatically and without complications. The greatest accepted dose – 450 mg. In view of the available experience, specific treatment is not necessary. It is unknown whether dialysis concerning removal from an organism of Simvalimita® and its metabolites is effective.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C.

To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.

On 3 planimetric packagings together with the application instruction in the state and Russian languages invest in a pack from a cardboard.