Simvalimit

Simvalymit is a drug from the subgroup of monocomponent drugs with hypolipidemic activity; it slows down one of the reductase subtypes. The main active element is simvastatin.

The administration of the drug helps to reduce the level of HDL-C and apolipoproteins, and also weakens the catabolism and production of LDL-C, while also affecting the levels of these components in the blood, changing the proportions of lipoproteins with different densities. [ 1 ]

Indications Simvalimit

It is used for hereditary forms of primary hypercholesterolemia of the homo- or heterozygous type, as well as for the combined form of hyperlipidemia, which cannot be corrected by diet or other non-drug methods.

It is prescribed for coronary heart disease with symptoms of hypercholesterolemia to reduce the likelihood of coronary death, myocardial infarction (non-fatal), stroke and risks during myocardial revascularization procedures, and in addition to slow the progression of coronary atherosclerosis.

Release form

The medicinal product is produced in the form of tablets - 10 pieces in a cell pack; there are 3 such packs in a box.

Pharmacodynamics

Simvastatin is a substance that regulates lipid levels. It is part of a subgroup of elements that inhibit HMG-CoA reductase (also called statins). Blockade of HMG-CoA reductase activity slows down the transformation of HMG-CoA into mevalonic acid (a precursor of cholesterol; cholesterol binding processes are mostly carried out inside the liver).

In plasma, statins reduce the level of total cholesterol, as well as LDL-C and VLDL-C. At the same time, they can reduce triglyceride values and slightly increase the HDL-C level. At the same time, the hypolipidemic effect of drugs from this category is realized through another mechanism. [ 2 ]

A decrease in intracellular cholesterol reserves within the hepatocyte wall leads to a compensatory increase in the number of LDL endings and also promotes the excretion of LDL from the blood. [ 3 ]

Pharmacokinetics

Simvastatin is absorbed in the gastrointestinal tract and after hydrolysis processes is transformed into an active element - β-hydroxy acid. Other metabolic products (active and inactive) are also released. The drug reaches plasma Cmax values in 1.3-2.4 hours.

Simvastatin has intensive metabolic processes during the first intrahepatic passage. Less than 5% of the orally administered portion penetrates into the bloodstream in the form of metabolically active components. Protein synthesis of simvastatin with β-hydroxy acid is 95%.

The drug enters the gastrointestinal tract in the form of metabolic products with bile; it is excreted mainly with feces. About 10-15% of the dosage is excreted with urine (most of it in the form of inactive metabolites). The half-life of active metabolic elements is 1.9 hours.

Dosing and administration

Before starting to use the medicine, the patient should start following a standard diet with reduced cholesterol levels (the regimen should be followed during the entire treatment cycle). The drug should be taken in the evening - before dinner or with it.

Use in individuals with a combined type of hyperlipidemia, primary hypercholesterolemia, and hereditary heterozygous hypercholesterolemia.

Use 10 mg of the substance once a day (in the evening). The portion is adjusted at least once a month. You can use 10-80 mg of the drug per day. You cannot exceed the daily dosage of 80 mg.

A hereditary form of homozygous hypercholesterolemia.

Take 40 mg once a day (in the evening), or use a regimen of 80 mg divided into 3 doses (20 mg in the morning and afternoon, and the remaining 40 mg in the evening).

Introduction to coronary heart disease.

At first, it is necessary to take 20 mg once a day, in the evening. Then the portion is changed (at least once a month). No more than 80 mg can be consumed per day (in 1 dose).

In case of combined use with fibrates, cyclosporine or niacin, which is used as a hypolipidemic substance, Simvalymit can be taken in a dose of no more than 10 mg per day.

Kidney failure.

In severe cases of the disorder (CC level <30 ml per minute), the initial dosage is 5 mg per day. Such patients should be closely monitored. No more than 10 mg of the drug is taken per day.

• Application for children

Use in pediatrics is prohibited because there is no reliable information regarding medicinal effects and safety.

Use Simvalimit during pregnancy

Cholesterol, along with other intermediates for its binding, are components that are necessary for fetal development (among other things, for binding cell walls and steroids). Because statins slow down the binding of cholesterol and other bioactive derivatives of cholesterol, they can cause fetal developmental disorders when administered to pregnant women. For this reason, statins are not used during pregnancy.

Therapy with statins in women of childbearing age requires the use of contraception during treatment and for 1 month after its completion. If pregnancy occurs during therapy, it is necessary to stop taking the drug.

Simvalimit is prohibited to use during breastfeeding. If there is a vital need to use the medicine, breastfeeding should be stopped for the duration of therapy.

Contraindications

Among the contraindications:

• severe intolerance associated with simvastatin or other components of the drug;
• active form of liver pathology or an increase in the activity of intraserum aminotransferases (of unknown origin);
• porphyria.

Side effects Simvalimit

Often, side effects of the drug include gastrointestinal disorders: abdominal pain, vomiting, bloating, diarrhea or constipation, and nausea.

Sometimes rashes, blurred vision, dizziness, dysgeusia, headaches and insomnia may develop.

Negative effects on muscles and liver are occasionally observed. Increased serum aminotransferase activity is possible.

There are reports of the occurrence of hepatitis, jaundice or pancreatitis, as well as intolerance syndrome with the development of Quincke's edema.

Myopathy may develop, manifested as myositis, myalgia, and muscle weakness, along with a concomitant increase in CPK activity, especially in individuals using simvastatin in combination with fibrates, erythromycin, immunosuppressants, niacin, and itraconazole.

Polyneuropathy and paresthesia may occur.

There is evidence of the development of secondary renal failure and rhabdomyolysis.

Overdose

There are isolated cases of poisoning with Simvalimit, but no specific signs were found; the patients' condition always stabilized after symptomatic procedures.

In case of overdose, standard measures are taken (induction of vomiting, administration of activated charcoal, monitoring of vital organs). In addition, renal/liver function and serum creatine kinase values should be monitored.

Interactions with other drugs

Grapefruit juice increases plasma levels of simvastatin.

The antibiotics erythromycin with clarithromycin, nefazodone, which is an antidepressant, the antimycotics ketoconazole with itraconazole and other triazole derivatives with imidazole, cyclosporine (an immunosuppressant), antiviral drugs (slowing down the action of viral proteases) and other substances that reduce lipid levels (niacin with fibrates) can increase the likelihood of myopathy.

The combination of statins with anticoagulants that are derivatives of oxycoumarin (for example, warfarin with acenocoumarol) may provoke an increase in the likelihood of bleeding and the PT index.

Combining Simvalymit with coumarin anticoagulants (for example, warfarin or acenocoumarol) or changing the dose of simvastatin requires constant monitoring of the PTT level before the start of treatment and during the treatment cycle. Once stable values are achieved, it is then monitored at intervals prescribed to individuals taking anticoagulants.

Use of the drug together with digoxin may lead to an increase in the plasma level of the latter, which can cause vomiting, nausea and arrhythmia.

Storage conditions

Simvalimit should be stored in a dark place, protected from moisture and small children. Temperature level – no more than 25°C.

Shelf life

Simvalimit can be used for a period of 24 months from the date of manufacture of the medicinal product.

Analogues

The analogs of the drug are the substances Simvor, Simgal with Simvastatin, Simvastol and Vasilip with Ovencor, as well as Simvageksal, Zocor and Actalipide.