Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
A hypolipidemic agent from the group of statins, an inhibitor of HMG-CoA reductase. It is a prodrug, since it has in its structure a closed lactone ring, which after hydrolysis into the body is hydrolyzed.
The lactone ring of statins is similar in structure to the portion of the HMG-CoA reductase enzyme. According to the principle of competitive antagonism, the statin molecule binds to that part of the coenzyme A receptor where this enzyme is attached. Another part of the statin molecule inhibits the conversion of hydroxymethylglutarate to mevalonate, an intermediate in the synthesis of the cholesterol molecule. Inhibition of the activity of HMG-CoA reductase results in a series of consecutive reactions that result in a decrease in intracellular cholesterol and a compensatory increase in LDL receptor activity and, accordingly, acceleration of LDL cholesterol catabolism (Xc).
The hypolipidemic effect of statins is associated with a decrease in the level of total cholesterol due to Xc-LDL. The decrease in LDL is dose-dependent and has a non-linear, but an exponential nature.
Statins do not affect the activity of lipoprotein and hepatic lipases, they do not have a significant effect on the synthesis and catabolism of free fatty acids, so their effect on the level of TG is secondary and mediated through their main effects on lowering the level of LDL-C. The moderate decrease in TG levels in statin therapy appears to be due to the expression of the receptor (apo E) receptors on the surface of hepatocytes participating in the catabolism of the disease, which includes approximately 30% TG.
According to controlled studies, simvastatin increases HDL-C level to 14%.
In addition to hypolipidemic action, statins have a positive effect on endothelial dysfunction (preclinical signs of early atherosclerosis), on the vascular wall, atheroma state, improve the rheological properties of blood, and have antioxidant, antiproliferative properties. There is evidence that simvastatin improves endothelial function after 30 days of therapy.
The use of simvastatin was accompanied by a decrease in the incidence of cardiovascular disorders, regardless of the baseline level of LDL-C.
PHARMACOKINETICS
After oral administration, simvastatin is well absorbed from the digestive tract (an average of 85%). C max is achieved after 4 hours. The intake immediately before eating with a low fat content does not affect the pharmacokinetic parameters of simvastatin.
When "first pass" through the liver, simvastatin is biotransformed to form active beta-metabolites. Binding to plasma proteins is 95%.
The concentration of the active metabolite of simvastatin in the systemic blood flow is less than 5%.
It is excreted unchanged in the form of metabolites, mainly with bile - 60-85%; 10-15% - in the form of inactive metabolites is excreted by the kidneys.
INDICATIONS
Primary hypercholesterolemia with ineffective diet, combined hypercholesterolemia and hypertriglyceridemia.
DOSING MODE
Individual. The initial dose is 5-20 mg. If necessary, increase the dose with an interval of 4 weeks. Simvastatin is taken 1 time / day, in the evening. The maximum doseis 40 mg / day.
For patients receiving immunosuppressants, the recommended initial dose is 5 mg / day; the maximum dose is 5 mg / day.
In severe renal failure (QC less than 30 ml / min), the initial dose is 5-10 mg / day.
SIDE EFFECT
On the part of the digestive system: constipation, diarrhea, loss of appetite, flatulence, nausea, abdominal pain, pancreatitis, increased activity of ALT, AST, GGT, APF.
From the central nervous system and peripheral nervous system: headache, dizziness, muscle cramps, paresthesia, peripheral neuropathy.
From the side of the cardiovascular system: transient arterial hypotension is possible.
From the musculoskeletal system: myalgia, myopathy, rhabdomyolysis, increased activity of CK.
Allergic reactions: rarely - angioedema, lupus-like syndrome, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis, urticaria, fever, dyspnea.
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.
PREGNANCY AND LACTATION
Simvastatin is contraindicated in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution apply simvastatin in severe renal failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated with an active pathological process in the liver, a persistent increase in the activity of transaminases.
APPLICATION FOR CHILDREN
Safety and effectiveness of the use of simvastatin in pediatric practice have not been established. It is not recommended for use in children.
SPECIAL INSTRUCTIONS
With caution use simvastatin in patients with liver disease, with chronic alcoholism, with arterial hypotension, decreased or increased tone of skeletal muscles of unclear etiology, with epilepsy, severe renal failure.
Before and during the treatment, liver function control is necessary.
In patients receiving anticoagulants produced by coumarin, prothrombin time should be monitored before and during treatment with simvastatin.
The use of simvastatin should be discontinued with a significant increase in CKK activity or suspected myopathy, with the development of acute or severe disease, with the appearance of any risk factor predisposing to the development of renal failure due to rhabdomyolysis.
It is not recommended to use simvastatin concomitantly with immunosuppressants, fibrates, nicotinic acid (in doses causing lipid lowering), antifungal preparations with azole derivatives.
Use in Pediatrics
Safety and effectiveness of the use of simvastatin in pediatric practice have not been established. It is not recommended for use in children.
DRUG INTERACTION
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 increases the risk of myopathy.
With simultaneous use with digoxin, the concentration of digoxin in the blood plasma increases.
A case of the development of rhabdomyolysis symptoms after a single dose of sildenafil in a patient receiving simvastatin is described.
