Simvagexal

Simvagexal contains the element simvastatin - a hypocholesterolemic substance obtained by synthesis from the fermentation products of ground aspergillus.

Simvastatin is used in the treatment of primary type hypercholesterolemia (if diet does not lead to the desired effect). The drug is highly effective in reducing the values of LDL and total cholesterol during non-familial and familial hypercholestrinemia, and in addition, hyperlipidemia of a mixed nature; in these cases, increased cholesterol levels act as a risk factor for the appearance of atherosclerotic vascular lesions. [1]

Indications Simvagexal

It is used in coronary artery disease to reduce the likelihood of myocardial infarction and coronary death. In addition, it is used to prevent stroke and temporary disorders of blood flow inside the brain, reduce the risk of needing surgery to restore coronary blood flow (CABG and PTCA), and reduce the rate of progression of coronary atherosclerosis (preventing the development of general vascular occlusion and the emergence of new disorders).

In persons with primary type hypercholesterolemia or its familial form (homo- or heterozygous), as well as with combined type hyperlipidemia, the drug is used as an adjunct to diet therapy - to reduce the increased index of total cholesterol, LDL-C, triglycerides and apolipoprotein B (in situations where when diet and other non-medicinal methods do not bring results).

Release form

The release of the therapeutic substance is made in tablets - 10 pieces inside a blister pack; inside the box - 3 such packages.

Pharmacodynamics

After ingestion, simvastatin, which is an inactive lactione, is converted by hydrolysis into its active form (β-hydroxyl) - the main metabolic component, as well as a substance that slows down HMG-CoA reductase (an enzyme that catalyzes the formation of mevalonate together with HMG-CoA, as well as limiting the initial stage of cholesterol biosynthesis).

The active form of the active substance of the drug is a specific inhibitor of the action of HMG-CoA reductase, due to which the principle of the effect of simvastatin is mainly associated with the destruction of cholesterol binding inside the liver in the mevalonic acid phase. [2]

In the case of using a daily dosage in the range of 10-80 mg, Simvagexal reduces the plasma values of total cholesterol, as well as the level of VLDL and LDL. At the same time, by reducing the plasma triglyceride levels, the drug simultaneously slightly increases the anti-atherogenic HDL values. [3]

Due to the fact that the formation of the bond between mevalonate and HMG-CoA is carried out at an early stage of cholesterol biosynthesis, therapy with the introduction of simvastatin does not lead to the accumulation of potentially toxic and dangerous sterols inside the body. In addition, HMG-CoA is rapidly transformed into acetyl-CoA, an element that is actively involved in most of the body's biosynthesis processes.

During use in persons with hypertriglyceridemia (triglyceride levels more than 2.25 mmol / l), the drug reduces these values within the blood plasma by 30%.

Simvastatin does not lead to increased biliary secretion, which is why its administration does not increase the risk of developing cholecystitis.

A tangible effect from therapy is noted after 14 days; the maximum medicinal effect is observed in the period of 1-1.5 months from the moment of the start of treatment, remaining during its continuation. After discontinuation of therapy, the overall level of cholesterol returns to the values noted at the beginning of the course.

Pharmacokinetics

After the introduction of drugs, the active substance is well absorbed from the gastrointestinal tract, penetrating into the circulatory system. Protein synthesis is equal to 95%. The Cmax values of active inhibitors inside the blood plasma are recorded after 1-2 hours from the moment the medication is used.

Simvastatin with its metabolic components is excreted mainly in the bile. The term half-life of substances that inhibit HMG-CoA reductase from the systemic circulation is approximately 2 hours.

The indicator of the active metabolic element of simvastatin within the systemic circulation is less than 5% of the administered portion.

Excretion in the urine takes 96 hours and is less than 0.5% of the dosage of drugs in the form of elements that slow down HMG-CoA reductase.

Dosing and administration

Before starting the use of Simvagexal, it is necessary to prescribe a standard hypocholesterol dietary regimen to the patient, which must be observed during therapy. Take the tablets 1 time per day, in the evening, without reference to food intake; the tablet is swallowed without chewing and washed down with plain water.

In the case of ischemic heart disease, the initial dosage is 20 mg, with one dose per day (in the evening). The dosage should be changed based on the plasma values of cholesterol, with a frequency of at least 1 time per month. A maximum of 80 mg of the substance is allowed per day, once (in the evening). If the LDL value drops to less than 75 mg / dL or the total plasma cholesterol level falls below 140 mg / dL, you need to gradually reduce the dose of the drug at the same frequency as when it was increased.

For the treatment of hyperlipidemia, you must first take 10 mg of the medication (1 time per day, in the evening).

For persons with a moderate or mild form of hypercholesterolemia, it is first recommended to use 5 mg of the drug, in the evening, 1 time per day; in this case, the drug is combined with non-drug methods of therapy (for example, weight loss and physical activity).

In the familial form of homozygous hypercholesterolemia, the medication is used in a portion of 40 mg (in the evening, 1 time per day); or a scheme is used with the introduction of 80 mg per day in 3 doses - 20 mg in the morning and in the afternoon, as well as 40 mg in the evening.

• Application for children

The medication is not prescribed in pediatrics.

Use Simvagexal during pregnancy

It is forbidden to use Simvagexal during pregnancy.

Contraindications

The main contraindications:

• severe intolerance associated with the elements of the drug;
• active hepatic pathologies or an unreasonable increase in the values of plasma transaminases;
• myopathy;
• use together with itraconazole, ketoconazole or drugs that slow down the action of HIV protease;
• GW period;
• the introduction of immunosuppressants or the presence of transplanted organs in the patient.

It is allowed to use the medicine in women of reproductive age only if contraceptives are used.

Side effects Simvagexal

The medication is generally tolerated without complications. Side signs are often mild and quickly disappear after a dosage reduction or drug withdrawal. These violations include:

• systemic disorders: asthenia sometimes develops;
• problems with the gastrointestinal tract: often there is nausea, stomach pain, constipation and bloating. Sometimes gastric disturbances, diarrhea and vomiting are observed;
• violations of hepatic function: hepatitis, jaundice or pancreatitis develops singly;
• manifestations associated with NS: sometimes headaches occur. Paresthesias, dizziness and polyneuropathy are singly noted;
• disorders affecting the hematopoietic system: anemia is observed singly;
• epidermal lesions: Sometimes an epidermal rash, itching, or eczema develops. Alopecia is singularly noted;
• dysfunction of muscles and bones: myalgitis or myositis appears singly, an active form of muscle necrosis or muscle cramps;
• renal dysfunction: a single failure of the kidneys occurs.

Occasionally, with the introduction of simvastatin, the appearance of erectile dysfunction was noted.

In addition, there are sporadic data on the appearance of a drug intolerance syndrome. Among its symptoms are vasculitis, Quincke's edema, rheumatoid polyneuralgia, lupus-like syndrome, arthritis, photophobia, dyspnea, thrombocytopenia, arthralgia, facial flushing, eosinophilia, malaise and fever.

Laboratory test data.

An increase in the values of GGT and alkaline phosphatase is noted. There may be a persistent increase in transaminase activity, more than three times the maximum normal value. The administration of the drug can provoke an insignificant temporary increase in serum CPK values (in the CC fraction) obtained from the skeletal muscles.

Negative symptoms that develop for unknown reasons.

There is sporadic information about the appearance of purpura, different types of erythema (among them SJS), leukopenia, and depression.

Overdose

There was no development of specific signs of poisoning when taking drugs. Dizziness, weakness, and allergy symptoms in the form of rash and itching may occur; in addition, disorders of the gastrointestinal tract develop - vomiting with nausea and stomach pain.

In case of intoxication, it is necessary to take measures for the excretion of the drug (gastric lavage and the use of activated carbon within half an hour after the use of drugs) and symptomatic procedures, and at the same time monitor the activity of transaminases (in the hospital).

Interactions with other drugs

Gemfibrozil, along with other fibrates, and in addition, lipid-lowering portions of niacin (> 1 g per day) do not affect the pharmacokinetics of simvastatin. But if they are used in combination with this substance, the likelihood of developing myopathy increases - because of this, such a combination should be avoided.

Also, you can not use the medication together with niacin and fibrates, if the positive effect of the subsequent change in lipid values does not exceed the increased risk of complications with this combination.

When niacin and fibrates are supplemented with substances that slow down the action of HMG-CoA reductase, there is an insignificant additional decrease in total LDL-C; in addition, there may be a further decrease in triglyceride values and an additional increase in HDL-C.

When using one of the above agents in combination with simvastatin, the likelihood of developing myopathy is lower than in the case of the combined administration of simvastatin, niacin and fibrates.

People who use fibrates, cyclosporin or niacin with Simvagexal should use simvastatin in portions of no more than 10 mg per day, because at a higher dosage, the likelihood of myopathy increases markedly.

Interaction of medication and hemoprotein P4 50 3A4.

Simvastatin does not have a retarding effect on the P450 3A4 hemoprotein, as well as the effect of drugs on the plasma values, whose metabolic processes are realized with the help of the P450 3A4 hemoprotein.

In this case, simvastatin acts as a substrate for the specified hemoprotein. Elements with a strong inhibitory effect on the hemoprotein P450 3A4 are capable of increasing the likelihood of myopathy, increasing the activity of substances that inhibit HMG-CoA reductase within the plasma when using simvastatin. These inhibitors include ketoconazole, clarithromycin with cyclosporine, erythromycin and itraconazole, as well as nefzodone with inhibitors of HIV protease activity.

The combination of a drug with itraconazole, ketoconazole and drugs that slow down the HIV protease is prohibited. Caution should be exercised when administered with nefazodone, clarithromycin, or erythromycin.

Grapefruit juice contains one or more elements that slow down the activity of hemoprotein P450 3A4, which is why it can increase the plasma level of drugs, whose metabolic processes are carried out using the specified cytochrome. It is required to stop taking juice during therapy with Simvagexal.

Coumarin derivatives.

In persons using coumarin anticoagulants, it is required to monitor PTT values before starting the administration of simvastatin, as well as during the period of its use - in order to confirm the absence of significant deviations in PTV values.

When using drugs in persons who did not use coagulants, there was no change in the level of PTT or the appearance of bleeding.

Digoxin.

The use of the drug together with digoxin causes a slight increase (less than 0.3 ng / ml) in the plasma parameters of the latter.

Cholestyramine with colestipol.

The drug must be used 1 hour before or after 4 hours after the introduction of the above substances - this will prevent a decrease in the absorption rate of simvastatin.

Antipyrine.

Antipyrine is a model of the metabolic processes of drugs using the hepatic enzymatic system of microsomes (structure of hemoprotein P450 3A4). There is a weak or moderate effect of simvastatin in relation to the pharmacokinetic parameters of antipyrine in people with hypercholesterolemia.

Storage conditions

Simvagexal should be stored in a place protected from moisture, sunlight and small children. Temperature level - no more than 30 ° С.

Shelf life

Simvagexal can be applied within a 24-month term from the date of manufacture of the pharmaceutical substance.

Analogs

Analogues of drugs are Simgal, Simvor with Simvastatin, Ovenkor and Aktalipid with Vasilip, and in addition Simvastol with Zokor.