SIMVASTATIN

Active material: Simvastatin
When ATH: C10AA01
CCF: Lipid-lowering drugs
When CSF: 01.12.11.03
Manufacturer: ALSI Pharma Company Inc. (Russia)

Pharmaceutical form, composition and packaging

Pills, covered film-coated from Brown to light brown with a pinkish tint, round, lenticular.

Excipients: microcrystalline cellulose, lactose, pre-gelatinized starch (starch 1500), colloidal silicon dioxide (aэrosyl), vitamin C, ʙutilgidroksianizol, stearic acid, magnesium stearate, opadraj II (polyvinyl alcohol, macrogol (polyethylene glycol), dye iron oxide black, talc, dye iron oxide yellow, iron oxide red dye, Titanium dioxide).

10 PC. – packings Valium planimetric (1) – packs cardboard.
10 PC. – packings Valium planimetric (2) – packs cardboard.
10 PC. – packings Valium planimetric (3) – packs cardboard.
10 PC. – packings Valium planimetric (4) – packs cardboard.
10 PC. – packings Valium planimetric (5) – packs cardboard.

Pills, Film-coated from Brown to light brown with a pinkish tint, round, lenticular.

[Ring] microcrystalline cellulose, lactose, pre-gelatinized starch (starch 1500), colloidal silicon dioxide (aэrosyl), vitamin C, ʙutilgidroksianizol, stearic acid, magnesium stearate, opadraj II (polyvinyl alcohol, macrogol (polyethylene glycol), dye iron oxide black, talc, dye iron oxide yellow, iron oxide red dye, Titanium dioxide).

10 PC. – packings Valium planimetric (1) – packs cardboard.
10 PC. – packings Valium planimetric (2) – packs cardboard.
10 PC. – packings Valium planimetric (3) – packs cardboard.
10 PC. – packings Valium planimetric (4) – packs cardboard.
10 PC. – packings Valium planimetric (5) – packs cardboard.

DESCRIPTION OF ACTIVE SUBSTANCES.

Pharmacological action

Lipid-lowering agents of the statin, , HMG-CoA reductase. It is a prodrug, because it has a closed ring laktonovoe, after intake of the hydrolyses.

Laktonovoe ring of Statins in its structure is similar to the part of the enzyme HMG-CoA reductase inhibitors. On the principle of competitive antagonism statina molecule binds with the receptor of Coenzyme a, where the enzyme is attached. Another part of the statin molecule inhibits the process of converting to mevalonate gidroksimetilglutarata, intermediate in the synthesis of cholesterol molecules. Inhibition of HMG-CoA reductase leads to a series of successive reactions, resulting in reduced intracellular cholesterol and takes a compensatory increase in the activity of LDL receptors and consequently accelerate the catabolism of cholesterol (Xc) LDL.

Lipid-lowering effect of statins is associated with a reduction in total cholesterol by LDL-C. Lowering LDL cholesterol is dose-dependent and is not linear, and the exponential nature.

Statins do not affect the activity of lipoprotein lipase and hepatic, no significant effect on the synthesis and catabolism of free fatty acids, so their impact on the level of a second Tg and indirectly through their major effects on the reduction of LDL-C. A moderate reduction in triglycerides in the treatment of statins, apparently, associated with expression remnantnyh (apo E) receptors on the surface of hepatocytes, involved in the catabolism of LPPP, a composition which approximately 30% TG.

According to controlled studies simvastatin increases the level of HDL Cholesterol to 14%.

In addition to lipid-lowering action, Statins have a positive impact in the endothelial dysfunction (preclinical signs of early atherosclerosis), on the vascular wall, state of atheroma, improve the rheological properties of blood, have antioxidant, antiproliferative properties. There is evidence, that simvastatin improves endothelial function after 30 days of therapy.

Application of simvastatin was accompanied by a decrease in the frequency of cardio-vascular disorders regardless of baseline LDL-Cholesterol.

Pharmacokinetics

After intake of simvastatin is well absorbed from the digestive tract (average 85%). C_max achieved through 4 no. Admission directly to the food with a low fat diet does not affect the pharmacokinetic parameters simvastatin.

At “first pass” through the liver biotransformiroetsa education simvastatin active metabolite beta. Plasma protein binding is 95%.

Simvastatin active metabolite concentration in the systemic blood is less 5%.

Write, unedited, and in the form of metabolites, mainly, the bile – 60-85%; 10-15% – in the form of inactive metabolites excreted kidneys.

Testimony

Primary giperholesterinemia with poor diet, combined giperholesterinemia and gipertriglitzeridemia.

Dosage regimen

Individual. The initial dose is 5-20 mg. If necessary, increase the dose at intervals of 4 of the week. Simvastatin is taken in 1 time / day, in the evening. The maximum dose is 40 mg / day.

Patient, receiving immunosuppressants, The recommended starting dose is 5 mg / day; the maximum dose – 5 mg / day.

In severe renal failure (CC less than 30 ml / min) starting dose is 5-10 mg / day.

Side effect

From the digestive system: constipation, diarrhea, loss of appetite, flatulence, nausea, stomach ache, pancreatitis, increased ALT, IS, GGT, Alkaline phosphatase.

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

Cardio-vascular system: possible transient hypotension.

On the part of the musculoskeletal system: mialgii, myopathy, raʙdomioliz, Increase CPK activity.

Allergic reactions: rarely – angioedema, lupus-like syndrome, vasculitis, thrombocytopenia, eozinofilija, increased erythrocyte sedimentation rate, arthritis, hives, fever, breathlessness.

Dermatological reactions: photosensitivity, skin rash, itch, dermahemia, alopecia.

Other: anemia.

Contraindications

Active pathological process in the liver, persistent increase in transaminaz, pregnancy, lactation, hypersensitivity to simwastatino.

Pregnancy and lactation

Simvastatin is contraindicated for use in pregnancy and lactation.

Cautions

Be wary used simvastatin in patients with liver diseases, with chronic alcoholism, When arterial hypotension, reduced or increased tone skeletal muscles unclear etiology, epilepsy, severe renal insufficiency.

Before and during treatment needed to be monitored liver.

Patients, receiving anticoagulants coumarin derivatives technology, before and during treatment simvastatinom should monitor prothrombin time.

Application of simvastatin should stop with a substantial increase in CPK activity or suspected myopathy, with the development of acute or severe disease, When you see any risk factor, predisposing to the development of kidney failure due to rhabdomyolysis.

It is not recommended to apply the simvastatin simultaneously with immunodepressantami, fiʙratami, nicotinic acid (doses, cause gipolipidemiju), anti-fungal drugs derivatives azola.

Use in Pediatrics

Safety and efficacy of simvastatin in paediatric practice not installed. Not recommended for use in children.

Drug Interactions

While applying the anti proximity amplifies (incl. varfarina).

Together with the use of cytostatics, itraconazole, fiʙratami, Nicotinic Acid in high doses, immunodepressantami increases the risk of myopathy.

In an application with digoxin increases the concentration of digoxin in the blood plasma.

Case of developing symptoms of rhabdomyolysis after receiving a single dose of sildenafila patients, receive simvastatin.