Vasilip, 20 mg 28 pcs.

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

The lactone ring of statins is similar in structure to the 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 is attached. The other part of the statin molecule inhibits the conversion of hydroxymethylglutarate into 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 of intracellular cholesterol content and a compensatory increase of LDL-receptor activity and corresponding acceleration of LDL cholesterol (Xc) catabolism.

The hypolipidemic effect of statins is associated with a decrease in total Xc levels at the expense of LDL Xc. The decrease in LDL levels is dose-dependent and has an exponential rather than linear character. Statins do not affect the activity of lipoprotein and hepatic lipases, have no significant effect on synthesis and catabolism of free fatty acids, so their effect on TG level is secondary and mediated through their main effects on reduction of LDL-C level. A moderate decrease in TG levels during treatment with statins seems to be due to the expression of remnant (apo E) receptors on the surface of hepatocytes involved in catabolism of LDL, which includes approximately 30% of TG. According to controlled studies, simvastatin increases HDL-C levels by up to 14%.

In addition to hypolipidemic action, statins have a positive effect in endothelial dysfunction (preclinical sign of early atherosclerosis), on the vascular wall, atheroma condition, improve rheological properties of blood, have antioxidant, antiproliferative properties. There is evidence that simvastatin improves endothelial function already after 30 days of therapy. The use of simvastatin was accompanied by a decrease in the incidence of cardiovascular disorders regardless of the initial level of CH-LDL.

Indications

Cholesterol Reduction, Thrombosis Prevention, CholesterolPrimary hypercholesterolemia with ineffective diet therapy, combined hypercholesterolemia and hypertriglyceridemia.

Active ingredient

Simvastatin

Composition

1 tablet contains:

The active ingredient:

simvastatin – 20 mg.

Excipients:

Lactose monohydrate;

Pregelatinized starch;

butylhydroxyanisole;

Anhydrous citric acid;

ascorbic acid;

p> corn starch;

MCC;

magnesium stearate.

Film coating:

Hypromellose; talc; propylene glycol; titanium dioxide.

How to take, the dosage

Individual.

The initial dose is 5-20 mg. If necessary, the dose is increased at intervals of 4 weeks.

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; the maximum dose is 5 mg/day.

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

Interaction

Pharmacodynamic

Concomitant use of simvastatin with fibrates, nicotinic acid (more than 1 g/day) increases the risk of myopathy, including rhabdomyolysis (when combined with fenofibrate – no increased risk of myopathy compared to monotherapy with each drug separately has been proved). Concomitant use with gemfibrozil may lead to increased serum concentrations of simvastatin.

Pharmacokinetic

. Cytochrome CYP3A4 inhibitors (itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors and nefazodone), which are involved in metabolic transformation of simvastatin in liver, increase risk of myopathy and rhabdomyolysis during simvastatin therapy. Simultaneous use with these drugs is contraindicated. Caution – when concomitant use with less strong CYP3A4 inhibitors: cyclosporine, verapamil and diltiazem. The daily dose of simvastatin in concomitant use with cyclosporine should not exceed 10 mg. The daily dose of simvastatin during concomitant administration of amiodarone or verapamil should not exceed 20 mg and 40 mg during concomitant administration of diltiazem, unless the expected benefit clearly exceeds the potential risk of myopathy and rhabdomyolysis.

Simvastatin at a dose of 20-40 mg/day in volunteers and patients with hypercholesterolemia potentiates the effects of coumarin anticoagulants (e.g., warfarin), in particular increases in PV, MHO. Therefore, in patients taking coumarin anticoagulants, PV and MHO should be determined before the start of simvastatin therapy, during the initial treatment period, when changing the dose of simvastatin or discontinuing the drug. When stable PV and MHO are achieved, further monitoring should be performed at intervals recommended for patients receiving anticoagulant therapy. Simvastatin therapy does not cause changes in PV and risk of bleeding in patients not taking anticoagulants.

Grapefruit juice inhibits the activity of CYP3A4. Simultaneous intake of large amounts of grapefruit juice (more than 1 liter per day) and simvastatin leads to a significant increase in plasma concentration of simvastatin acid. Therefore, grapefruit juice should be avoided during simvastatin therapy.

Special Instructions

In patients with decreased thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) when cholesterol levels increase, therapy of the underlying disease should be given first.

Patients with severe renal insufficiency should be treated under control of renal function.

Women of reproductive age must use reliable contraception during treatment with Vasilip^®.

The treatment with simvastatin, like other HMG-CoA reductase inhibitors, may cause myopathy, sometimes leading to rhabdomyolysis with or without renal failure due to myoglobinuria. The risk of myopathy increases with increasing dose of simvastatin and in patients with severe renal failure.

The treatment with simvastatin may increase serum CPK, which should be considered in the differential diagnosis of chest pain and after intense physical activity.

People should be advised of the risk of myopathy and the need to seek immediate medical attention if there is unexplained muscle pain, tension or weakness, especially if accompanied by malaise or fever, before initiating therapy with Vasilip^® or increasing its dose.

The baseline CPK level before starting therapy should be determined in the following situations:

• in elderly patients;
• in renal impairment;
• in decompensated hypothyroidism;
• with a strong family history of hereditary muscle disease;
• with a history of toxic muscle exposure to statins or fibrates;
• with alcohol abuse.

In these cases, the possible risk and expected benefit should be assessed, and clinical monitoring during therapy is recommended. If baseline CPK level is significantly elevated (more than 5 times the upper limit of normal), measurement should be repeated in 5-7 days to confirm the results. In case of confirmation of a significant initial increase of CPK level (more than 5 times the upper limit of normal), the drug is not recommended to be administered.

Before and during treatment, the patient should be on a hypocholesterolemic diet.

During treatment with Vasilip^®, if muscle pain, weakness or cramps occur, the CPK level should be determined. The criterion for discontinuation of the drug is an increase in serum CPK levels by more than 5 times the upper limit of normal. If muscle symptoms are strongly pronounced and cause discomfort, even with CPK levels 5 times below the upper limit of normal, it may be necessary to stop treatment. If myopathy is suspected, therapy should be stopped, regardless of the cause of myopathy.

If symptoms disappear and CPK levels return to normal, the statin or an alternative drug of the same class may be prescribed again at the lowest clinically effective dose and under close medical supervision.

The therapy with Vasilip^® should be temporarily discontinued several days before major surgical procedures.

Patients with severe renal insufficiency should be treated under monitoring of renal function.

Measures to reduce the risk of myopathy caused by drug interactions

The risk of myopathy and rhabdomyolysis is significantly increased with concomitant use of simvastatin and potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nephazodone), gemfibrozil or cyclosporine (see “Interactions”). section “Interactions”). The risk of myopathy and rhabdomyolysis is also increased when concomitant use of fibrates and high doses of nicotinic acid (1 g/day) or when concomitant therapy with amiodarone or verapamil with high doses of simvastatin (see section “Interaction”). The risk also increases slightly with concomitant administration of diltiazem and high doses of simvastatin (80 mg).

Hence, the simultaneous use of simvastatin with itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors and nefazodone is contraindicated (see section “Contraindications”). If therapy with the listed CYP3A4 inhibitors cannot be refused, simvastatin should be withheld. Simvastatin should also be combined with caution with some other, less potent CYP3A4 inhibitors: cyclosporine, verapamil and diltiazem (see section “Interactions”).

Concomitant administration of simvastatin and grapefruit juice should be avoided.

In patients taking cyclosporine, gemfibrozil or high doses of nicotinic acid (>1 g/day), the daily dose of simvastatin should not exceed 10 mg.

The concomitant administration of simvastatin and gemfibrozil is possible only in cases where the expected benefits significantly exceed the potential risk of such a drug combination. The benefits of the combined use of simvastatin 10 mg/day and other fibrates (except fenofibrate), nicotinic acid (>1 g/day) or cyclosporine should be carefully weighed against the potential risks of such combinations.

There is a risk of myopathy when fenofibrate and simvastatin are administered separately, so caution is necessary when this combination is taken concomitantly.

The concomitant use of amiodarone or verapamil should be avoided when taking simvastatin in doses greater than 20 mg/day, unless the expected benefit exceeds the potential risk of myopathy.

The effect on the liver

The treatment with simvastatin may cause an increase in the activity of hepatic enzymes in the blood serum. This increase is usually mild and clinically insignificant. After discontinuation of the drug, transaminase levels usually decrease slowly to baseline levels. Nevertheless, liver function tests should be performed before starting treatment and thereafter (monitor liver transaminase activity every 6 weeks during the first 3 months, then every 8 weeks during the remaining first year and then once every 6 months). If it is necessary to increase the dose up to 80 mg, liver function monitoring is mandatory before increasing the dose, 3 months after the increase and then periodically (e.g. once every 6 months) during the first year of treatment. In case of persistent 3-fold increase in serum ACT and/or ALT activity relative to the upper limit of normal, treatment with simvastatin should be discontinued.

With caution is administered to persons who abuse alcohol and/or have a history of liver disease.

Impact on the ability to drive a car or perform work requiring increased speed of physical and mental reactions.

There have been no reports of adverse effects of the drug Vasilip^® on the ability to drive and operate machinery. Nevertheless, it should be taken into account that single cases of dizziness have been reported during postmarketing use of simvastatin.

Contraindications

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

Side effects

Gastrointestinal tract, liver: rarely – constipation, abdominal pain, flatulence, dyspepsia, nausea, vomiting, diarrhea, pancreatitis, hepatitis, jaundice, increased activity of liver transaminases, ALP, creatine phosphokinase (CPK).

CNS, peripheral nervous system and sensory organs: rarely – headache, paresthesia, dizziness, peripheral neuropathy, asthenia, insomnia, seizures, blurred vision, taste disorders.

Musculoskeletal system: rarely – myopathy, rhabdomyolysis, myalgia, muscle weakness.

Allergic and immunopathological reactions: Deployed hypersensitivity syndrome (angioneurotic edema, lupus-like syndrome, rheumatic polymyalgia, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, increased erythrocyte sedimentation rate (ESR), arthritis, arthralgia, urticaria, photosensitivity, fever, flushes, shortness of breath and pronounced weakness).

Dermatological reactions: rarely – skin rash, itching, alopecia.

Others: rare – anemia; palpitation, acute renal failure (due to rhabdomyolysis), decreased potency.

Overdose

Symptoms: There are data on several cases of simvastatin overdose. The maximum dose taken was 3.6 g.

Treatment: in case of overdose symptomatic treatment is provided; general measures should be taken: monitoring and maintenance of vital functions, prevention of further drug absorption (gastric lavage, administration of activated charcoal or laxatives). Monitoring of liver function and CPK is recommended. There is no specific antidote.

If myopathy with rhabdomyolysis develops (a rare but severe side effect), the drug should be stopped immediately, a diuretic and sodium bicarbonate should be administered to the patient (IV infusion). Rhabdomyolysis may cause hyperkalemia, which can be eliminated by IV administration of calcium chloride and calcium gluconate, glucose infusion with insulin, use of potassium ion exchangers or, in severe cases, with hemodialysis.

Pregnancy use

The drug is contraindicated in pregnancy. There is no evidence of increased incidence of birth defects in children whose mothers have taken simvastatin or other HMG-CoA reductase inhibitor. If a pregnant woman takes simvastatin, fetal levels of mevalonate, which is a precursor of cholesterol biosynthesis, may decrease. Withdrawal of hypolipidemic agents in pregnancy has no significant effect on the results of short-term risk associated with primary hypercholesterolemia.

Simvastatin should not be used in pregnant women, women planning to become pregnant or if pregnancy is suspected. If pregnancy occurs during treatment, the drug should be withdrawn and the woman should be warned about the possible danger to the fetus.

It is not known whether the drug is excreted into the breast milk, therefore therapy with Vasilip® during breastfeeding is contraindicated.

Similarities

Simvastatin