Simvahexal^® (Tablets) Instructions for Use

ATC Code

C10AA01 (Simvastatin)

Active Substance

Simvastatin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Hypolipidemic agent

Pharmacotherapeutic Group

Hypolipidemic agent – HMG-CoA reductase inhibitor

Pharmacological Action

Hypolipidemic agent from the group of statins, an inhibitor of HMG-CoA reductase. It is a prodrug because it has a closed lactone ring in its structure, which is hydrolyzed after entering the body.

The lactone ring of statins is structurally similar to a part of the HMG-CoA reductase enzyme. By the principle of competitive antagonism, the statin molecule binds to the part of the coenzyme A receptor where this enzyme attaches. The other part of the statin molecule inhibits the process of converting hydroxymethylglutarate to mevalonate, an intermediate product in the synthesis of the cholesterol molecule. Inhibition of HMG-CoA reductase activity leads to a series of sequential reactions, resulting in a decrease in intracellular cholesterol content and a compensatory increase in LDL receptor activity and, accordingly, an acceleration of LDL cholesterol (C) catabolism.

The hypolipidemic effect of statins is associated with a decrease in total C levels due to LDL-C. The decrease in LDL levels is dose-dependent and is not linear but exponential.

Statins do not affect the activity of lipoprotein and hepatic lipases, do not significantly affect the synthesis and catabolism of free fatty acids, so their effect on TG levels is secondary and mediated through their main effects on reducing LDL-C levels. The moderate decrease in TG levels during treatment with statins appears to be associated with the expression of remnant (apo E) receptors on the surface of hepatocytes involved in the catabolism of IDL, which contain approximately 30% TG.

According to controlled studies, Simvastatin increases HDL-C levels by up to 14%.

In addition to the hypolipidemic effect, statins have a positive effect on endothelial dysfunction (a preclinical sign of early atherosclerosis), on the vascular wall, the condition of the atheroma, improve the rheological properties of blood, and have antioxidant and antiproliferative properties. There is evidence that Simvastatin improves endothelial function as early as 30 days of therapy.

The use of simvastatin was accompanied by a reduction in the frequency of cardiovascular disorders regardless of the initial LDL-C level.

Pharmacokinetics

After oral administration, Simvastatin is well absorbed from the gastrointestinal tract (on average 85%). C_max is reached after 4 hours. Taking it immediately before a low-fat meal does not affect the pharmacokinetic parameters of simvastatin.

During the “first pass” through the liver, Simvastatin is biotransformed to form active beta-metabolites. Plasma protein binding is 95%.

The concentration of the active metabolite of simvastatin in the systemic bloodstream of humans is less than 5%.

It is excreted unchanged and as metabolites, mainly with bile – 60-85%; 10-15% is excreted by the kidneys as inactive metabolites.

Indications

Primary hypercholesterolemia when diet therapy is ineffective, combined hypercholesterolemia and hypertriglyceridemia.

ICD codes

Dosage Regimen

Tablets

Individual. The initial dose is 5-20 mg. If necessary, the dose is increased at 4-week intervals. Simvastatin is taken once a day, in the evening. The maximum dose is 40 mg/day.

For patients receiving immunosuppressants, the recommended initial dose is 5 mg/day; maximum dose – 5 mg/day.

In severe renal failure (creatinine clearance less than 30 ml/min), the initial dose is 5-10 mg/day.

Adverse Reactions

From the digestive system constipation, diarrhea, loss of appetite, flatulence, nausea, abdominal pain, pancreatitis, increased activity of ALT, AST, GGT, ALP.

From the central and peripheral nervous system headache, dizziness, muscle cramps, paresthesia, peripheral neuropathy.

From the cardiovascular system transient arterial hypotension is possible.

From the musculoskeletal system myalgia, myopathy, rhabdomyolysis, increased CPK activity.

Allergic reactions rarely – angioedema, lupus-like syndrome, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis, urticaria, fever, shortness of breath.

Dermatological reactions photosensitivity, skin rash, itching, skin hyperemia, alopecia.

Other anemia.

Contraindications

Active pathological process in the liver, persistent increase in transaminase activity, pregnancy, lactation, hypersensitivity to simvastatin.

Use in Pregnancy and Lactation

Simvastatin is contraindicated for use during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in active pathological process in the liver, persistent increase in transaminase activity.

Use in Renal Impairment

Simvastatin should be used with caution in severe renal failure.

Pediatric Use

The safety and efficacy of simvastatin use in pediatric practice have not been established. Not recommended for use in children.

Special Precautions

Simvastatin should be used with caution in patients with liver disease, with chronic alcoholism, with arterial hypotension, decreased or increased skeletal muscle tone of unclear etiology, with epilepsy, severe renal failure.

Liver function monitoring is necessary before starting and during treatment.

In patients receiving coumarin derivative anticoagulants, prothrombin time should be monitored before starting and during treatment with simvastatin.

Simvastatin should be discontinued if there is a significant increase in CPK activity or suspicion of myopathy, if an acute or severe illness develops, or if any risk factor appears that predisposes to the development of renal failure due to rhabdomyolysis.

It is not recommended to use Simvastatin simultaneously with immunosuppressants, fibrates, nicotinic acid (in doses that cause a hypolipidemic effect), antifungal drugs of the azole derivative group.

Use in pediatrics

The safety and efficacy of simvastatin use in pediatric practice have not been established. Not recommended for use in children.

Drug Interactions

With simultaneous use, the effect of indirect anticoagulants (including warfarin) is enhanced.

With simultaneous use with cytostatics, itraconazole, fibrates, nicotinic acid in high doses, immunosuppressants, the risk of developing myopathy increases.

With simultaneous use with digoxin, the concentration of digoxin in the blood plasma increases.

A case of development of rhabdomyolysis symptoms after a single dose of sildenafil in a patient receiving Simvastatin has been described.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.