Allesta

Allesta is a hypolipidemic monocomponent drug from a subgroup of substances that slow down the effect of HMG-CoA reductase.

Simvastatin is a non-active lactone that readily undergoes hydrolysis with subsequent in vivo transformation into β-hydroxy acid (it noticeably slows down the activity of HMG-CoA reductase). The hydrolysis carried out has mainly an intrahepatic pathway; its plasma velocity is very low. [1]

It was determined that simvastatin reduces the standard, and with this increased levels of LDL cholesterol. LDL elements are formed from VLDL; their catabolism mainly occurs with the participation of endings with significant affinity for the LDL elements.

Indications Allesta

Hypercholesterolemia .

It is used for primary hypercholesterolemia or mixed dyslipidemia - as an addition to the ongoing diet, in cases where the reaction to diet and other non-drug methods of therapy (for example, weight loss and physical activity) is not effective enough.

It can be used in the case of a familial form of hypercholesterolemia (homozygous form) - to supplement diet and other methods of lipid-lowering therapy (this includes apheresis associated with LDL) or in situations where these treatments do not help.

It is prescribed for prophylaxis in case of problems with the activity of the CVS.

Allows to reduce the likelihood of death in people with CVS diseases, as well as morbidity in people with severe atherosclerotic CVS lesions or diabetes mellitus (with standard or increased cholesterol values) - additional treatment that helps to correct other risk factors and other cardioprotective procedures.

Release form

The release of the medicinal substance is realized in tablets with a volume of 10 and 20 mg (10 pieces inside a cell package; 3 packages inside a pack), as well as 40 mg (15 pieces inside a blister pack; 2 packs inside a box).

Pharmacodynamics

The principle of the development of the LDL-reducing effect of simvastatin may include a decrease in VLDL cholesterol levels, as well as stimulation of the activity of LDL endpoints, causing a decrease in the production and an increase in the catabolism of LDL cholesterol. Apolipoprotein B values also decrease significantly during simvastatin use.

Along with this, simvastatin significantly increases the level of HDL cholesterol and reduces intraplasmic triglyceride levels. Such changes cause a decrease in the proportions of systemic cholesterol in relation to HDL cholesterol, and with it LDL cholesterol in relation to HDL cholesterol.

Pharmacokinetics

Suction.

The absorption of simvastatin in humans proceeds well enough, with the passage of primary extensive intrahepatic metabolic processes. The secretion of drugs into the liver is determined by the intensity of the hepatic circulation. The main activity of the drug develops inside the liver. It was determined that the level of availability of β-hydroxy acid for passage into the systemic circulation with oral administration of simvastatin is less than 5% of the dosage.

The Cmax values of inhibitors with activity inside the blood plasma are determined approximately after 1-2 hours from the moment of drug administration. Eating food does not alter absorption. Pharmacokinetic characteristics of the substance with the introduction of single and multiple doses show that the drug does not cumulate in the case of multiple doses.

Distribution processes.

Inside the blood plasma, simvastatin and its metabolic element (with therapeutic activity) are synthesized with protein by> 95%.

Excretion.

Simvastatin is a substrate for the CYP3A4 component. The main metabolic elements of simvastatin in human blood plasma are β-hydroxy acid, as well as 4 additional metabolic products with activity.

After ingestion of a portion of the radioactive active element of the drug, for a period of 96 hours, 60% of the labeled substance was excreted with feces, and another 13% - along with urine. The volume found inside the feces is equivalent to the absorbed substance secreted from the bile, and in addition to the unabsorbed element.

With the on / in the introduction of the metabolite of β-hydroxy acid, the term of its half-life was on average 1.9 hours. In the form of inhibitors, only 0.3% of the dosage is excreted in the urine on average.

Dosing and administration

The medication is taken orally, once a day, in the evening; the serving size range ranges from 5 to 80 mg. The dosage is selected with at least 1-month intervals until the maximum daily portion of 80 mg is received (it is administered in the evening, once a day). A dosage of 80 mg is used only in persons with severe hypercholesterolemia and a very high probability of complications in the work of the CVS, for whom the required effect does not develop when using lower portions (also in cases where the probable advantages are more expected than the risks of negative consequences).

Hypercholesterolemia.

A standard diet is carried out aimed at reducing the level of cholesterol (it must be observed during the entire period of therapy with the introduction of simvastatin). Basically, the size of the initial dosage is 10-20 mg per day (1-time dose in the evening). For individuals who require a significant (over 45%) decrease in LDL-C, the starting portion may be 20-40 mg with 1-time evening intake. If the dosage selection is required, it is performed according to the above scheme.

Familial form of hypercholesterolemia (homozygous).

First, you need to use 40 mg of the substance once a day (in the evening). Simvastatin is used as an adjunct to other lipid-lowering therapy (for example, LDL apheresis) or when such therapy is impossible.

Prevention of diseases associated with the function of the CVS.

Often, people with a high likelihood of coronary artery disease (in combination with hyperlipidemia or not) are used 1 time in the evening for 20-40 mg of the drug. Medication treatment can be combined with exercise and diet. If the selection of dosages is required, it is carried out according to the scheme described above.

Complementary treatment.

Simvastatin demonstrates good efficacy as monotherapy, and in addition, in combination with bile acid sequestrants. It is necessary to use drugs at least 2 hours before the introduction of sequestrants or after at least 4 hours after their use.

In persons who use Allesta together with fibrates (except for gemfibrozil) or fenofibrate, the dose of simvastatin is a maximum of 10 mg per day. In people taking the drug in combination with verapamil, amiodarone, diltiazem or amlodipine, this dosage per day is no more than 20 mg.

Serving sizes for kidney failure.

In people with severe kidney failure, the drug is used with extreme caution - no more than 10 mg per day.

Use in pediatrics (10-17 years of age).

For children in the age range of 10-17 years with a familial type of hypercholesterolemia (heterozygous), first use a 10 mg portion with 1 evening use per day. Before starting therapy, the child is prescribed a standard diet aimed at lowering the level of cholesterol (it must be observed for the entire period of the treatment course).

Usually used daily dosages in the range of 10-40 mg; 40 mg is the highest serving per day. The selection of dosages is carried out personally, taking into account the purpose of treatment and the recommendations of therapy for the pediatric group. Portions are selected at minimum 1-month intervals.

• Application for children

The therapeutic efficacy and safety indicators of simvastatin use in persons 10-17 years old with a familial form of hyperlipidemia (heterozygous) was studied during controlled clinical testing, in which boys (Tanner age phase 2 and above), as well as girls who already at least 1 year of menstruation. The statistics for adverse events in people using simvastatin did not generally differ from those in people who received placebo. Administration of portions exceeding 40 mg has not been tested in this category of treatment. During this testing, no effect of simvastatin was found on puberty and growth in children, as well as on the length of the menstrual cycle.

Girls need to be informed about the use of contraception during therapy using Allesta. In persons under the age of 18, the safety and efficacy of the drug over a period of more than 48 weeks have not been studied; there is no information on the long-term possible consequences associated with physical, sexual and mental development.

The effect of drugs has not been investigated in persons under the age of 10, girls before the onset of menstruation and children in the prepubertal period.

Use Allesta during pregnancy

You can not use simvastatin during pregnancy, because there is no proven information regarding the safety of its appointment during the specified period - controlled clinical trials with the participation of pregnant women have not been performed. Occasionally, information appeared about the appearance of congenital anomalies in the case of exposure of agents that slow down HMG-CoA reductase inside the womb. But the analysis of information obtained during observations of approximately 200 pregnant women who used simvastatin or other similar substances that slow down HMG-CoA reductase in the 1st trimester showed that the incidence of congenital anomalies roughly corresponds to the frequency observed in the general population.

But it should be borne in mind that when using simvastatin, a decrease in fetal indicators of mevalonate (a precursor of cholesterol biosynthesis) may be observed. Atherosclerosis is a chronic process, so often the abolition of lipid-lowering medications during pregnancy has some effect on the long-term risks associated with primary hypercholesterolemia. Because of this, it is forbidden to use simvastatin in pregnant women, if there is a suspicion of pregnancy, as well as during its planning. Therapy using this substance must be stopped for the period of gestation or until the moment when pregnancy is completely excluded.

There is no information about whether the drug is excreted with mother's milk. Because many medicines can be excreted in milk, and in addition, due to the high likelihood of severe side symptoms in women using simvastatin, breastfeeding should be stopped for the period of treatment.

Contraindications

The main contraindications:

• severe intolerance associated with simvastatin or other elements of the medication;
• hepatic pathologies in the active phase or persistent increase in serum transaminase values of an unknown nature;
• administration together with potent inhibitors of the action of CYP3A4 (drugs that increase the AUC level by about five times or higher). These include ketoconazole and voriconazole with itraconazole and posaconazole, boceprevir and clarithromycin with nefazodone; the list also includes erythromycin, telaprevir with telithromycin and agents that slow down the activity of HIV protease (among them nelfinavir);
• use in combination with cyclosporine or gemfibrozil, as well as danazol.

Side effects Allesta

Among the side effects:

• disorders associated with the blood system and lymph: rarely anemia occurs;
• problems affecting the psyche: insomnia appears occasionally. Depression may develop;
• disorders of the activity of the National Assembly: paresthesias, headaches, polyneuropathy and dizziness are occasionally observed. A single memory disorder develops;
• lesions associated with the organs of the mediastinum and sternum or with the respiratory system: the appearance of interstitial pulmonary disease is possible;
• disturbances in the digestive tract: occasionally bloating, diarrhea, abdominal pain, constipation, vomiting, dyspepsia, pancreatitis and nausea are noted;
• problems with hepatobiliary activity: occasionally jaundice or hepatitis occurs. Single - failure of hepatic activity (possibly fatal);
• lesions of the epidermis with the subcutaneous layer: occasionally itching, rash or alopecia appears;
• disorders of the functioning of connective tissues and muscle structure with the skeleton: rarely, myopathy (may include myositis), myalgia, rhabdomyolysis (supplemented or not supplemented with acute renal failure) and muscle spasms are noted. Development of tendinopathy is possible, which is sometimes complicated by rupture;
• problems affecting the mammary glands and fertility: impotence may occur;
• systemic manifestations: asthenia is occasionally observed;
• severe intolerance syndrome: occasionally dermatomyositis, eosinophilia, Quincke's edema, polymyalgia, rheumatic in nature, thrombocytopenia, lupus-like syndrome, urticaria, arthralgia, hot flashes, increased ESR marks, and in addition, arthritis, fever and photosensitivity, nondibomies
• change in test readings: occasionally there is an increase in serum values of transaminases (AST, ALT, and also GGT), creatine kinase and ALP.

The use of statins, among which simvastatin, can cause an increase in Hba1c values, as well as serum glucose when administered on an empty stomach.

There is evidence of the development of cognitive dysfunctions (for example, forgetfulness, confusion, memory loss or memory disorder) that were caused by taking statins (also simvastatin). Usually these cases were mild and reversible, disappearing after the statin use was discontinued.

There were isolated reports of the development of IONM, myopathy of an autoimmune nature, which was caused by the use of statins. With IONM, weakness in the proximal muscle and an increase in serum creatine kinase levels (this process persists even when statin administration is canceled) is observed, and in addition, symptoms of necrotizing myopathy according to muscle biopsy data develop (without severe inflammation) and improvement in connection with treatment with immunosuppressants.

The use of certain statins can cause the following additional negative signs:

• sleep disorders, including nightmares;
• disorder of sexual activity;
• diabetes mellitus: the likelihood of its development is determined by the absence or presence of risk factors (fasting blood glucose values ≥5.6 mmol / L, BMI> 30 kg / m2, a history of increased blood pressure and elevated triglycerides).

Overdose

At the moment, there is information on several cases of Allesta poisoning. The highest dosage accepted was 3600 mg. The recovery of all such patients passed without the development of negative consequences.

There is no specific therapy for intoxication - supportive and symptomatic actions are carried out.

Interactions with other drugs

Pharmacodynamic parameters of interaction.

The likelihood of developing myopathy (also includes rhabdomyolysis) increases when the drug is combined with fibrates. In addition, an interaction with the substance gemfibrozil develops, causing an increase in the plasma values of simvastatin.

In some cases, rhabdomyolysis or myopathy develops due to the combination of the drug with lipid-modifying portions (≥1 g per day) of niacin.

Pharmacokinetic characteristics of the interaction.

Use in combination with substances that have a strong inhibitory effect on the activity of CYP3A4 (among them voriconazole and itraconazole with posaconazole and ketoconazole, and in addition clarithromycin and erythromycin with telithromycin), and in addition with boceprevir, cyclosporin, telaprevir and danazib, and, nefazodone and HIV protease inhibitors (including nelfinavir) are prohibited.

When combined with other fibrates (except fenofibrate), you can use no more than 10 mg of simvastatin per day.

It is prohibited to use the medicine together with fusidic acid.

When prescribed in combination with amlodipine, diltiazem, as well as amiodarone and verapamil, the daily dosage of the drug should be a maximum of 20 mg.

During treatment with Allesta, you should not drink grapefruit juice.

Storage conditions

Allesta should be kept in a place closed from the penetration of small children. Temperature level - maximum 25 ° C.

Shelf life

Allesta can be used within a 24-month term from the date of manufacture of the medicinal substance.

Analogs

The analogues of the drug are Zokor, Vasilip, Simvatin with Vasostat, and in addition Simvastatin and Simvastat.