Simvastatin

Simvastatin is an agent that reduces serum triglycerides and cholesterol levels. In addition, the drug slows down the action of HMG-CoA reductase.

Orally taken simvastatin, which is an inactive lactone, participates in intrahepatic hydrolysis with the formation of the corresponding type of active β-hydroxy acid (it potently inhibits the activity of HMG-CoA reductase). This enzyme catalyzes the transformation of HMG-CoA into mevalonate - at an early stage, limiting the processes of cholesterol biosynthesis. [1]

Indications Simvastatin

It is used in the case of the primary stage of hypercholesterolemia or a mixed form of dyslipidemia - as an addition to the dietary regimen (in situations where other non-drug methods - such as weight loss and physical activity - do not work).

It is prescribed for the treatment of a hereditary type of homozygous type of hypercholesterolemia - in addition to diet and other lipid-lowering procedures (for example, LDL apheresis) or in cases where these methods of treatment are ineffective.

Primary and secondary prevention of cardiovascular complications in persons with coronary artery disease or diabetics.

Release form

The release of a therapeutic element is made in the form of tablets with a volume of 10, 20 or 40 mg - 14 pieces each inside a cell package. A pack contains 2 such packages.

Pharmacodynamics

Simvastatin is able to reduce the values of cholesterol (both increased and normal) and LDL. The principle of the therapeutic effect, which reduces the level of LDL, consists of a reduction in LDL-C, as well as LDL endings - this causes a decrease in the production and increased catabolism of LDL-C.

The introduction of drugs also significantly reduces the values of apolipoprotein B. At the same time, the drug moderately increases the values of HDL-C and lowers the plasma triglyceride values. [2]

Pharmacokinetics

The hydrolysis of the substance occurs in vivo with the formation of the corresponding β-hydroxy acid. The hydrolysis process is mainly carried out inside the liver; the intraplasmic development of hydrolysis occurs at a very low rate.

The medicine is well absorbed inside the body. The active form of the substance first acts inside the liver. The rate of passage of β-hydroxy acid into the bloodstream after drug administration is less than 5% of the dosage. Plasma level Cmax of inhibitors with activity is noted after 1-2 hours from the moment of drug administration. Eating with food does not alter the intensity of absorption. [3]

Increasing the dose of the drug does not cause the accumulation of simvastatin. The level of protein synthesis of an active element with an active metabolic product is over 95%.

The half-life of simvastatin is within 1.3-3 hours.

Dosing and administration

The daily dosage is in the range of 5-80 mg (use in the evening, once a day). If you need to change the portion, it is carried out at least after 1 month (while it should be no more than 80 mg per day). Individuals with a severe stage of hypercholesterolemia and people with an increased likelihood of complications of the CVS function use a dosage of 80 mg.

Hypercholesterolemia.

It is necessary to follow a standard diet that helps to lower the cholesterol values (the regimen is adhered to for the entire period of therapy). The size of the initial dosage is in the range of 10-20 mg, once a day (taken in the evening).

For persons who need a significant decrease in the level of LDL-C (over 45%), you can start with 1-time intake per day (in the evening) 20-40 mg. If necessary, the dosage can be changed according to the scheme indicated above.

Hereditary type of homozygous hypercholesterolemia.

The size of the daily portion - taken in the evening 40 mg or the introduction of 80 mg for 3 uses (twice 20 mg, and then, in the evening - 40 mg).

Simvastatin is used in the form of an adjunct to therapy using other lipid-lowering methods (for example, the LDL apheresis procedure) or in situations where this method of therapy is not possible.

Prevention of the development of CVD diseases.

A standard daily dose of drugs (20-40 mg) for persons with a high probability of developing IHD complications (with or without hyperlipidemia) is administered in the evening, 1 time per day. Therapy can be started at the same time as exercise or diet. If you need to adjust the portion, it is carried out according to the scheme described above.

Concomitant treatment measures.

The drug is effective in monotherapy and when used in combination with bile acid sequestrants. It should be consumed at least 2 hours before or after at least 4 hours after the administration of sequestrants.

Use in people with impaired renal function.

If a person with a severe stage of impairment needs to take medicine (CC level <30 ml per minute), it is necessary to use extremely carefully daily portions of more than 10 mg.

• Application for children

There is no data on whether the drug will be safe and effective when administered to children. Because of this, it is not used in pediatrics.

Use Simvastatin during pregnancy

You can not use the medication during pregnancy, since the safety of its use during the indicated period has not been proven.

Contraindications

The main contraindications:

• severe sensitivity to simvastatin or other components of the medication;
• active stage of hepatic disease or a persistent increase in serum transaminases (regardless of the origin of the disorder);
• administration in combination with potent inhibitors of the CYP3A4 element (for example, ketoconazole with itraconazole, nefazodone, clarithromycin with erythromycin, HIV protease inhibitors and telithromycin).

Side effects Simvastatin

Dizziness, polyneuropathy, or headaches may develop. In addition, bloating, vomiting, dyspepsia, constipation, nausea, abdominal pain and diarrhea are possible. Anemia, pruritus, alopecia, rashes, jaundice, pancreatitis, or hepatitis may also develop. In addition, asthenia, myopathy, myalgia, muscle cramps and the active phase of skeletal muscle necrosis are possible.

Rarely, polymyalgia, vasculitis, lupus-like syndrome, dermatomyositis, photophobia, urticaria, and Quincke's edema are observed. In addition, there is hyperemia, arthralgia, malaise, arthritis, dyspnea and fever. There may be an increase in ESR, eosinophilia, and thrombocytopenia. An increase in the values of alkaline phosphatase, CPK and transaminases (AST with ALT and GGT) is possible.

Overdose

With prolonged use of Simvastatin, the risk of developing negative signs increases.

In case of poisoning, gastric lavage should be performed and activated charcoal should be used. Along with this, serum CPK values are monitored.

Interactions with other drugs

It is required to very carefully combine the drug with weaker inhibitors of the CYP3A4 substance (diltiazem, cyclosporine, amiodarone and verapamil), since this can increase the likelihood of acute necrosis of the skeletal muscles and the appearance of myopathy.

Grapefruit juice should not be consumed during Simvastatin therapy.

The combined use of daily dosages of drugs exceeding 20 mg with verapamil or amiodarone should be abandoned. The use is allowed only in situations where the benefits of such a combination are more likely than the possibility of myopathy.

People using coumarin anticoagulants need to determine the level of PTT before starting therapy, and then regularly monitor it at the initial stage of the course - to ensure that there is no significant alteration of these indicators.

Storage conditions

Simvastatin must be kept in a dark place out of the reach of small children. Temperature values - no more than 25 ° C.

Shelf life

Simvastatin is allowed to be used for a 36-month term from the date of manufacture of the medicinal product.

Analogs

The analogs of the drug are the substances Simvalimit, Vasilip, Simvastol with Zorstat, and besides this Simvagexal, Simgal with Avestatin, Simcard and Ovenkor. The list also includes Simlo, Aktalipid, Holvasim with Zokor, Atherostat, Simvor and Zovatin.

Reviews

Simvastatin receives mostly positive feedback from patients. It effectively helps to reduce the cholesterol index, is convenient to use and has a low cost. But in some comments the presence of pronounced side signs and the weakness of the therapeutic effect are noted.