Simvastatin

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

Orally administered simvastatin, an inactive lactone, undergoes intrahepatic hydrolysis to form 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 – an early stage that limits the processes of cholesterol biosynthesis. [ 1 ]

Indications Simvastatin

It is used in cases of primary hypercholesterolemia or mixed dyslipidemia – as an addition to a dietary regimen (in situations where other non-drug methods – such as weight loss and exercise – do not produce results).

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

Primary and secondary prevention of complications of the cardiovascular system in individuals with coronary heart disease or diabetics.

Release form

The therapeutic element is released in the form of tablets with a volume of 10, 20 or 40 mg - 14 pieces inside a blister pack. There are 2 such packs in a pack.

Pharmacodynamics

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

The administration of the drug also significantly reduces the values of apolipoprotein B. At the same time, the drug moderately increases the levels of HDL-C and reduces the plasma levels of triglycerides. [ 2 ]

Pharmacokinetics

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

The drug 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 blood system after the administration of the drug is less than 5% of the dosage. The plasma level of Cmax of inhibitors with activity is noted after 1-2 hours from the moment of administration of the drug. Use with food does not change the intensity of absorption. [ 3 ]

Increasing the doses of the drug does not cause accumulation of simvastatin. The level of protein synthesis of the active element with the 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 (taken in the evening, once a day). If a change in the dosage is required, it is carried out at least after 1 month (in this case, it should not exceed 80 mg per day). For people with severe hypercholesterolemia and people with an increased likelihood of complications of the cardiovascular system, a dosage of 80 mg is used.

Hypercholesterolemia.

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

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

A hereditary form of homozygous hypercholesterolemia.

The daily dose size is 40 mg taken in the evening or 80 mg administered in 3 doses (20 mg twice, then 40 mg in the evening).

Simvastatin is used as 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 development of cardiovascular diseases.

The standard daily dose of the drug (20-40 mg) for people with a high probability of developing complications of coronary heart disease (with or without hyperlipidemia) is administered in the evening, once a day. Therapy can be started simultaneously with exercise or diet. If there is a need to adjust the dose, it is carried out according to the scheme described above.

Concomitant treatment measures.

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

Use in people with renal impairment.

If a person with a severe stage of the disorder (creatinine clearance level <30 ml per minute) needs to take the drug, it is necessary to use daily doses greater than 10 mg with extreme caution.

• Application for children

There is no data on whether the drug is safe and effective when administered to children. For this reason, it is not used in pediatrics.

Use Simvastatin during pregnancy

The medication should not be used during pregnancy, since its safety during this period has not been proven.

Contraindications

Main contraindications:

• severe hypersensitivity to simvastatin or other components of the drug;
• active stage of liver disease or 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, substances that inhibit HIV protease and telithromycin).

Side effects Simvastatin

Dizziness, polyneuropathy, or headaches may develop. In addition, bloating, vomiting, dyspepsia, constipation, nausea, abdominal muscle pain, and diarrhea may occur. Anemia, itching, alopecia, rashes, jaundice, pancreatitis, or hepatitis may also develop. Asthenia, myopathy, myalgia, muscle cramps, and active skeletal muscle necrosis may also occur.

Polymyalgia, vasculitis, lupus-like syndrome, dermatomyositis, photophobia, urticaria and Quincke's edema are occasionally observed. In addition, hyperemia, arthralgia, malaise, arthritis, dyspnea and fever occur. ESR, eosinophilia and thrombocytopenia may be increased. ALP, CPK and transaminase values (AST with ALT and GGT) may increase.

Overdose

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

In case of poisoning, gastric lavage should be performed and activated carbon should be used. At the same time, serum CPK values should be monitored.

Interactions with other drugs

The drug should be combined with weaker CYP3A4 inhibitors (diltiazem, cyclosporine, amiodarone and verapamil) with extreme caution as this may increase the risk of acute skeletal muscle necrosis and myopathy.

When taking Simvastatin, do not drink grapefruit juice.

The combined use of daily doses of the drug exceeding 20 mg with verapamil or amiodarone should be avoided. Use is permitted only in situations where the benefit of such a combination is more likely than the possibility of myopathy.

People using coumarin anticoagulants should have their PT levels determined before starting therapy and then monitored regularly during the initial phase of therapy to ensure that there is no significant alteration in these levels.

Storage conditions

Simvastatin should be stored in a dark place, out of the reach of small children. Temperature values should not exceed 25 °C.

Shelf life

Simvastatin is approved for use for a period of 36 months from the date of manufacture of the medicinal product.

Analogues

The analogs of the drug are Simvalimit, Vasilip, Simvastol with Zorstat, and also Simvageksal, Simgal with Avestatin, Simcard and Ovencor. The list also includes Simlo, Actalipid, Kholvasim with Zocor, Aterostat, Simvor and Zovatin.

Reviews

Simvastatin generally receives positive reviews from patients. It effectively helps to reduce cholesterol levels, is easy to use, and has a low cost. However, some comments note the presence of pronounced side effects and the weakness of the therapeutic effect.