Simvagesal, 10 mg, 30 pcs.

SimvaGEXAL is a hypolipidemic.

The active metabolite inhibits 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase), the enzyme that catalyzes the initial reaction of mevalonate formation from HMG-CoA. Since the conversion of HMG-CoA to mevalonate represents an early step in cholesterol synthesis, the use of simvastatin does not cause accumulation of potentially toxic sterols in the body. HMG-CoA is easily metabolized to acetyl-CoA, which is involved in many synthesis processes in the body.

Causes a decrease in plasma levels of triglycerides (TG), low-density lipoproteins (LDL), very low-density lipoproteins (VLDL) and total cholesterol (in cases of heterozygous familial and non-family forms of hypercholesterolemia in mixed hyperlipidemia, when elevated cholesterol is a risk factor).

Enhances high-density lipoprotein (HDL) and decreases the ratio of LDL/HDL and total cholesterol/HDL.

Pharmacodynamics

The effect is seen 2 weeks from the start of administration, the maximum therapeutic effect is achieved after 4-6 weeks. The effect is maintained during continuation of treatment; when therapy is discontinued, cholesterol content gradually returns to baseline levels.

Pharmacokinetics

The absorption of simvastatin is high. After oral administration, C_max in plasma is reached after approximately 1.3-2.4 h and decreases by 90% after 12 h. Binding to plasma proteins is about 95%.

It is metabolized in the liver. There is a “first pass” effect through the liver (hydrolyzed with the formation of the active derivative – beta-hydroxy acid, as well as other active and inactive metabolites). T_1/2 of active metabolites is 1.9 h.

Extracted primarily with the feces (60%) as metabolites, about 10-15% – by the kidneys in the inactive form.

Indications

Active ingredient

Composition

1 tablet contains:

The active ingredient:

simvastatin 40 mg;

Associates:

corn starch,

lactose monohydrate,

microcrystalline cellulose,

ascorbic acid,

citric acid monohydrate,

magnesium stearate, hypromellose,

talk,

titanium dioxide,

iron (III) oxide.

How to take, the dosage

SimvAGEXAL should be taken orally once a day in the evening with plenty of water.

Hypercholesterolemia: Depending on the severity of hypercholesterolemia the initial dose is from 5 to 10 mg per day. The value of the dose is established on the basis of the results of values of cholesterol levels in plasma, obtained at intervals of at least 4 weeks. The usual daily dose is 40 mg simvastatin. In case of insufficient effectiveness and in the presence of cardiovascular risk it is allowed to increase the dose up to a maximum of 80 mg per day.

Ischemic heart disease: The initial dose is 20 mg. If necessary, the dose is gradually increased every 4 weeks to 40 mg. If LDL content is less than 75 mg/dL (1.94 mmol/L), and total cholesterol content is less than 140 mg/dL (3.6 mmol/L), the drug dose should be reduced.

For patients with chronic renal insufficiency (creatinine clearance less than 30 ml/min) or those concomitantly taking cyclosporine, fibrates or nicotinamide, the initial dose is 5 mg, and the maximum daily dose is 10 mg.
Against the background of immunosuppressive therapy, the recommended starting dose is 5 mg daily and the maximum daily dose is 5 mg daily.

Interaction

Cytostatics, antifungal drugs (ketoconazole, itraconazole), fibrates, high doses of nicotinic acid, immunosuppressants, erythromycin, clarithromycin, protease inhibitors increase the risk of rhabdomyolysis.

Results in increased effect of oral anticoagulants (e.g., phenprocoumon, warfarin) and increases the risk of bleeding, which requires monitoring blood clotting before treatment and regularly during treatment.

Elevates plasma levels of digoxin.

Colestyramine and colestipol decrease bioavailability (the use of simvastatin is possible 4 hours after taking these drugs, with an additive effect).

Special Instructions

At the beginning of therapy with simvastatin, a transient increase in liver enzymes (serum transaminase) is possible. Before the start of therapy and regularly thereafter – carry out liver function tests (monitor the activity of “liver” transaminases every 6 weeks for the first 3 months, then every 8 weeks for the remaining first year, and then once a year), as well as a liver function test should be performed when increasing doses.

If the dose is increased to 80 mg, a liver function test should be performed every 3 months. In case of a persistent increase in transaminase activity (3 times the baseline level), SimvAGEXAL should be discontinued. SimvaGEXAL, as well as other HMG-CoA reductase inhibitors, should not be used if there is an increased risk of rhabdomyolysis and renal failure (against the background of severe acute infection, arterial hypotension, planned major surgery, trauma, severe metabolic disorders). Cancellation of hypolipidemic agents during pregnancy has no significant effect on the results of long-term treatment of primary hypercholesterolemia.

Due to the fact that HMG-CoA reductase inhibitors inhibit cholesterol synthesis and cholesterol and other products of its synthesis play a significant role in fetal development, including steroid and cell membrane synthesis, simvastatin may have adverse effects on the fetus when prescribed to pregnant women (women of reproductive age should avoid conception). If pregnancy occurs during treatment, the drug should be withdrawn and the woman should be warned about the possible danger to the fetus. In patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) when cholesterol levels are elevated, the underlying disease should be treated first.

Patients should report any muscular manifestations to their physician. In order to diagnose the development of myopathy, regular measurements of CPK values are recommended. SimvAGEXAL is administered with caution to persons who abuse alcohol and/or have a history of liver disease. Before and during treatment the patient should be on a hypocholesterolemic diet.
Simultaneous intake of grapefruit juice may increase the severity of side effects associated with taking SimvAGEXAL, so they should be avoided.

In patients with myalgia, myasthenia and/or marked increase in CPK activity, the drug should be discontinued. SimvAGEXAL is not indicated in cases with hypertriglyceridemia of types I, IV and V. It is effective both as monotherapy and in combination with bile acid sequestrants. If the current dose is missed, the drug should be taken as soon as possible. If it is time to take the next dose, the dose should not be doubled. In patients with severe renal insufficiency, treatment is carried out under control of renal function. The duration of use of the drug is determined by the attending physician individually.

Contraindications

With caution: the drug should be administered to patients with chronic alcoholism; patients after organ transplantation who are treated with immunosuppressants (due to the increased risk of rhabdomyolysis and renal failure); in conditions that may lead to severe renal failure, such as arterial hypertension, acute infectious diseases of severe course, marked metabolic and endocrine disorders, disorders of water-electrolyte balance, surgical interventions (including

In case of epilepsy, patients with low or increased skeletal muscle tone of unknown etiology, children and adolescents under 18 years of age (safety and efficacy of use have not been established).

Side effects

Digestive system: possible abdominal pain, constipation, flatulence, nausea, diarrhea, dyspepsia, pancreatitis, vomiting, hepatitis, increased activity of liver transaminases, alkaline phosphokinase and creatine phosphokinase (CPK).

Nervous system and sensory organs: asthenic syndrome, headache, dizziness, insomnia, muscle cramps, paresthesias, peripheral neuropathy, blurred vision, taste disorders.

Allergic and immunopathologic reactions: rarely – angioedema, rheumatic polymyalgia, vasculitis, thrombocytopenia, increased sedimentation, fever, arthritis, urticaria, photosensitization, skin flushing, hot flashes, dyspnea, lupus-like syndrome, eosinophilia.

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

Motor system disorders: myopathy, myalgia, weakness; rhabdomyolysis rarely.

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

Overdose

None of the known few cases of overdose (maximum dose taken was 450 mg) showed specific symptoms.

Treatment: induce vomiting, take activated charcoal.

Symptomatic therapy: liver and renal function and serum creatine phosphokinase levels should be monitored.

Pregnancy use

SimvAGEXAL should not be taken during pregnancy.

There have been several reports of abnormalities in infants whose mothers have taken simvastatin. Women of childbearing age taking simvastatin should avoid conception.

If pregnancy does occur while taking the drug, SimvAGEXAL should be stopped, and the woman should be warned of the possible danger to the fetus.

There are no data on excretion of simvastatin with the mother’s milk.

If it is necessary to prescribe SimvAGEXAL to women during breastfeeding, it should be noted that many drugs are excreted with breast milk and there is a risk of severe reactions, so breastfeeding while taking the drug is not recommended.

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