Simvagexal

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

Simvastatin is used in the treatment of primary hypercholesterolemia (if diet does not produce the desired effect). The drug is highly effective in reducing LDL and total cholesterol levels in non-familial and familial hypercholesterolemia, as well as mixed hyperlipidemia; in these cases, elevated cholesterol levels act as a risk factor for the development of atherosclerotic vascular lesions. [ 1 ]

Indications Simvagexal

It is used in coronary heart disease to reduce the risk 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 the coronary form of atherosclerosis (prevention of the development of general vascular occlusion and the appearance of new disorders).

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

Release form

The therapeutic substance is released in tablets - 10 pieces inside a blister pack; inside a box - 3 such packs.

Pharmacodynamics

After oral administration, simvastatin, which is an inactive lactone, is converted by hydrolysis into its active form (β-hydroxyl), which is the main metabolic component and also a substance that inhibits HMG-CoA reductase (an enzyme that catalyzes the reaction of mevalonate formation together with HMG-CoA, and also limits 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, which is why the principle of action of simvastatin is mainly associated with the destruction of cholesterol binding inside the liver in the mevalonic acid phase. [ 2 ]

In case of using a daily dosage within 10-80 mg, Simvaghexal reduces plasma values of total cholesterol, as well as the level of VLDL and LDL. At the same time, reducing the values of plasma triglycerides, the drug simultaneously slightly increases the values of antiatherogenic HDL. [ 3 ]

Since the formation of the bond between mevalonate and HMG-CoA occurs 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 in the body. In addition, HMG-CoA is quickly transformed into acetyl-CoA, an element that actively participates in most biosynthesis processes in the body.

When used in individuals with hypertriglyceridemia (triglyceride levels over 2.25 mmol/l), the drug reduces these values in blood plasma by 30%.

Simvastatin does not increase bile secretion, which is why its administration does not increase the risk of developing cholecystitis.

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

Pharmacokinetics

After administration of the drug, the active substance is well absorbed from the gastrointestinal tract, penetrating into the circulatory system. Protein synthesis is 95%. The Cmax values of active inhibitors in the blood plasma are recorded after 1-2 hours from the moment of administration of the drug.

Simvastatin and its metabolic components are excreted mainly with bile. The half-life of substances inhibiting HMG-CoA reductase from the systemic circulation is approximately 2 hours.

The amount of the active metabolic element simvastatin in the systemic circulation is less than 5% of the administered dose.

Excretion with urine occurs within 96 hours and is less than 0.5% of the drug dosage in the form of elements that inhibit HMG-CoA reductase.

Dosing and administration

Before starting to use Simvageksal, it is necessary to prescribe a standard hypocholesterol dietary regimen to the patient, which must also be followed during therapy. Tablets should be taken once a day, in the evening, without reference to food intake; the tablet is swallowed without chewing and washed down with plain water.

In case of coronary heart disease, the initial dosage is 20 mg, taken once a day (in the evening). The dosage should be changed based on the plasma cholesterol values, at least once a month. A maximum of 80 mg of the substance is allowed per day, taken once (in the evening). If the LDL level has dropped to less than 75 mg / dL or the total plasma cholesterol level has fallen below 140 mg / dL, it is necessary to gradually reduce the dose of the drug with the same frequency as when increasing it.

To treat hyperlipidemia, you must first take 10 mg of the medication (once a day, in the evening).

For individuals with moderate or mild hypercholesterolemia, it is recommended to initially take 5 mg of the drug in the evening, once a day; in this case, the drug is combined with non-drug therapies (for example, weight loss and exercise).

In the case of familial hypercholesterolemia of the homozygous type, the medication is taken in a dose of 40 mg (in the evening, 1 time per day); or a regimen is used with the introduction of 80 mg per day in 3 doses - 20 mg in the morning and during the day, and 40 mg in the evening.

• Application for children

The medication is not prescribed in pediatrics.

Use Simvagexal during pregnancy

It is prohibited to use Simvaghexal during pregnancy.

Contraindications

Main contraindications:

• severe intolerance associated with the components of the drug;
• those with active liver pathologies or an unexplained increase in plasma transaminase levels;
• myopathy;
• use with itraconazole, ketoconazole, or HIV protease inhibitors;
• breastfeeding period;
• the introduction of immunosuppressants or the presence of transplanted organs in the patient.

The use of the drug in women of reproductive age is permitted only if they are using contraceptives.

Side effects Simvagexal

The medication is generally tolerated without complications. Side effects are often mild and quickly disappear after reducing the dosage or stopping the medication. Among such disorders:

• systemic disorders: sometimes asthenia develops;
• problems with the gastrointestinal tract: nausea, stomach pain, constipation and bloating often occur. Sometimes stomach problems, diarrhea and vomiting are observed;
• liver dysfunction: occasionally hepatitis, jaundice or pancreatitis develops;
• manifestations associated with the nervous system: headaches sometimes occur. Paresthesia, dizziness and polyneuropathy are observed sporadically;
• disorders affecting the hematopoietic system: anemia is observed sporadically;
• Epidermal lesions: sometimes epidermal rash, itching or eczema develops. Alopecia is observed sporadically;
• dysfunction of muscles and bones: myalgitis or myositis, active form of muscle necrosis or muscle cramps appear occasionally;
• renal dysfunction: renal failure occurs occasionally.

Erectile dysfunction has been reported in isolated cases with the administration of simvastatin.

In addition, there are isolated data on the occurrence of intolerance syndrome in relation to the drug. Among its symptoms are vasculitis, Quincke's edema, rheumatoid polyneuralgia, lupus-like syndrome, arthritis, photophobia, dyspnea, thrombocytopenia, arthralgia, facial flushes, eosinophilia, malaise and fever.

Laboratory test data.

Increases in GGT and ALP are noted. Persistent increases in transaminase activity, more than three times the maximum normal value, may occur. Administration of the drug may cause a minor, temporary increase in serum CPK (in the CK fraction) obtained from skeletal muscle.

Negative symptoms that develop for unknown reasons.

There is isolated information about the appearance of purpura, various types of erythema (including SSc), leukopenia, and depression.

Overdose

No specific signs of poisoning have been observed when taking the drug. Dizziness, weakness, and allergy symptoms in the form of rash and itching may be observed; in addition, gastrointestinal disorders develop - vomiting with nausea and stomach pain.

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

Interactions with other drugs

Gemfibrozil together with other fibrates, as well as lipid-lowering doses of niacin (>1 g per day) do not affect the pharmacokinetics of simvastatin. However, when used in combination with this substance, the likelihood of myopathy increases - for this reason, such a combination should be avoided.

The drug should also not be used together with niacin and fibrates unless the positive effect of the subsequent change in lipid values outweighs the increased risk of complications with this combination.

When niacin and fibrates are supplemented with substances that inhibit the action of HMG-CoA reductase, there is a slight additional decrease in total LDL-C levels; 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 combined administration of simvastatin, niacin and fibrates.

People using fibrates, cyclosporine or niacin together with Simvahexal should use simvastatin in doses of no more than 10 mg per day, because at higher doses the likelihood of myopathy increases significantly.

Interaction between the drug and hemoprotein P4 50 3A4.

Simvastatin has no inhibitory effect on hemoprotein P450 3A4, and also no effect on plasma levels of drugs whose metabolic processes are realized with the help of hemoprotein P450 3A4.

Simvastatin acts as a substrate for the said hemoprotein. Elements with a strong inhibitory effect relative to hemoprotein P450 3A4 can increase the likelihood of myopathy by enhancing the activity of substances that inhibit HMG-CoA reductase in plasma when using simvastatin. Among the said inhibitors are ketoconazole, clarithromycin with cyclosporine, erythromycin and itraconazole, as well as nefozodone with inhibitors of HIV protease activity.

Combination of the drug with itraconazole, ketoconazole and drugs that inhibit HIV protease is prohibited. Caution is required when administered with nefazodone, clarithromycin or erythromycin.

Grapefruit juice contains one or more elements that inhibit the activity of hemoprotein P450 3A4, due to which it can increase the plasma level of drugs whose metabolic processes are realized with the help of the specified cytochrome. It is necessary to refuse to take juice during therapy with Simvageksal.

Coumarin derivatives.

In individuals using coumarin anticoagulants, PT values should be monitored before starting simvastatin administration and during its use to confirm the absence of significant deviations in PT values.

When using the drug in individuals who did not use coagulants, no changes in the PT level or occurrence of bleeding were observed.

Digoxin.

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

Cholestyramine with colestipol.

The drug should be administered 1 hour before or 4 hours after the administration of the above substances - this will prevent a decrease in the intensity of absorption of simvastatin.

Antipyrine.

Antipyrine is a model of drug metabolism by the liver microsomal enzyme system (hemoprotein P450 3A4 structure). A weak to moderate effect of simvastatin on the pharmacokinetic parameters of antipyrine is observed in people with hypercholesterolemia.

Storage conditions

Simvageksal should be stored in a place protected from moisture, sunlight and small children. Temperature level – no more than 30°C.

Shelf life

Simvaghexal can be used within a 24-month period from the date of manufacture of the pharmaceutical substance.

Analogues

The analogs of the drug are Simgal, Simvor with Simvastatin, Ovencor and Actalipide with Vasilip, and in addition Simvastol with Zocor.