Simvastatin-ALSI pills 20mg, 30pcs

Composition

One film coated tablet contains:

Active ingredient:  

Simvastatin — 20 mg

Auxiliary substances:  

Microcrystalline cellulose — 140.00 mg

Lactose monohydrate — milk sugar) – 42.00 mg

Pregelatinized starch (starch 1500) – 67.46 mg

Colloidal silicon dioxide (aerosil) – 1.50 mg

Ascorbic acid — 5.00 mg

Butylhydroxyanisole-0.04 mg

Stearic acid-2.50 mg

Magnesium Stearate — 1.50 mg

Polyvinyl alcohol — 4.66 mg

Macrogol (polyethylene glycol) — 2.36 mg

Iron oxide black dye-0.04 mg

Talcum powder — 1.72 mg

Iron oxide yellow dye-0.56 mg

Iron oxide red dye-0.38 mg

Titanium Dioxide-1.94 mg

Pharmacological action

The hypolipidemic agent obtained synthetically from the fermentation product of Aspergillus terreus is an inactive lactone that undergoes hydrolysis in the body to form a hydroxy acid derivative.

The active metabolite inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase( HMG-CoA reductase), an enzyme that catalyzes the initial reaction of mevalonate formation from HMG-CoA.

Since the conversion of HMG-CoA to mevalonate is an early step in cholesterol synthesis, the use of Simvastatin does not cause the accumulation of potentially toxic sterols in the body. HMG-CoA is readily metabolized to acetyl-CoA, which is involved in many synthesis processes in the body.

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

Increases the content of high-density lipoproteins (HDL) and reduces the LDL ratio/HDL and total cholesterol/HDL.

The onset of the effect is 2 weeks after the start of treatment, and the maximum therapeutic effect is achieved in 4-6 weeks. The effect persists with continued treatment, and when therapy is stopped, the cholesterol content gradually returns to its original level.

Indications

Hypercholesterolemia:

• Primary hypercholesterolemia (type IIa and IIb) with the ineffectiveness of low-cholesterol diet therapy and other non-drug measures (physical activity and weight loss) in patients with an increased risk of coronary atherosclerosis;
• Combined hypercholesterolemia and hypertriglyceridemia, not corrected by special diet and exercise.

Coronary heart disease:

• For the prevention of myocardial infarction,
• To reduce the risk of death,
• Reducing the risk of cardiovascular disorders (stroke or transient ischemic attacks),
• Slowing the progression of coronary atherosclerosis,
• Reduce the risk of revascularization procedures.

Recommendations for use

Before starting treatment with Simvastatin, the patient should be prescribed a standard hypocholesterol diet, which should be followed throughout the course of treatment.

Simvastatin should be taken orally once a day in the evening, with a sufficient amount of water.

The time of taking the drug should not be associated with food intake.

The recommended dose of Simvastatin for the treatment of hypercholesterolemia varies from 10 to 80 mg once a day in the evening. The recommended starting dose for patients with hypercholesterolemia is 10 mg. The maximum daily dose is 80 mg.

Changes (selection) of the dose should be carried out at intervals of 4 weeks. In most patients, the optimal effect is achieved when taking the drug in doses up to 20 mg per day.

In patients with homozygous hereditary hypercholesterolemia, the recommended daily dose of Simvastatin is 40 mg once a day in the evening or 80 mg in three doses (20 mg in the morning,20 mg in the afternoon and 40 mg in the evening).

In the treatment of patients with coronary heart disease (CHD) or a high risk of CHD, the effective dose of Simvastatin is 20-40 mg per day. Therefore, the recommended starting dose in such patients is 20 mg per day. Changes (selection) of the dose should be carried out at intervals of 4 weeks, if necessary, the dose can be increased to 40 mg per day. If the LDL content is less than 75 mg/dl (1.94 mmol/L) and the total cholesterol content is less than 140 mg/dl (3.6 mmol/L), the dose of the drug should be reduced.

In elderly patients and in patients with mild or moderate renal insufficiency, no dosage changes are required.

In patients with chronic renal insufficiency (creatinine clearance less than 30 ml / min) or receiving cyclosporine, danazol, gemfibrozil or other fibrates (other than fenofibrate), nicotinic acid in lipid-lowering doses (≥ 1 g/day) in combination with Simvastatin, the maximum recommended dose of Simvastatin should not exceed 10 mg per day.

For patients taking amiodarone or verapamil concomitantly with Simvastatin, the daily dose should not exceed 20 mg.

Contraindications

• Hypersensitivity to simvastatin or other components of the drug (including hereditary lactose intolerance), as well as to other statin-type drugs (HMG-CoA reductase inhibitors) in the anamnesis;
• Liver diseases in the active phase, persistent increase in the activity of “liver” enzymes of unknown etiology;
• Skeletal muscle diseases (myopathy);
• Age up to 18 years (efficacy and safety have not been established).

Prescribe with caution to patients:

• Abusing alcohol
• Post-organ transplant patients undergoing immunosuppressant therapy (due to an increased risk of rhabdomyolysis and renal failure)
• For conditions that can lead to the development of severe renal insufficiency, such as arterial hypotension, severe acute infectious diseases, severe metabolic and endocrine disorders, water-electrolyte balance disorders, surgical interventions (including dental ones) or injuries
• Patients with reduced or increased skeletal muscle tone of unclear etiology;
• Epilepsy

Side effects

From the digestive system:  abdominal pain, constipation, flatulence, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increased activity of “liver” enzymes, alkaline phosphokinase and creatine phosphokinase (CPK) are possible.

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

Musculoskeletal disorders: myopathy, myalgia, muscle cramps, weakness; rarely-rhabdomyolysis.

Allergic and immunopathological reactions:  angioedema, polymyalgia rheumatoid, vasculitis, thrombocytopenia, increased ESR, fever, arthritis, urticaria, photosensitivity, skin hyperemia, hot flashes, shortness of breath, lupus-like syndrome, eosinophilia.

Dermatological reactions:  rarely skin rash, pruritus, alopecia, dermatomyositis.

Other services:  anemia, palpitations, acute renal failure (due to rhabdomyolysis), decreased potency.

Interaction

Cytostatics, antifungal agents (ketoconazole, itraconazole), fibrates, high doses of nicotinic acid, immunosuppressants, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone increase the risk of myopathy.

Cyclosporine or danazol: the risk of developing myopathy/rhabdomyolysis increases when cyclosporine or danazol is co-administered with high doses of Simvastatin.

Other lipid-lowering agents that can cause the development of myopathy: the risk of developing myopathy increases with the combined use of other lipid-lowering agents that are not powerful inhibitors of CYP3A4, but can cause myopathy in monotherapy. Such as gemfibrozil and other fibrates (other than fenofibrate), as well as nicotinic acid at a dose of ≥ 1 g per day.

Amiodarone and verapamil: the risk of developing myopathy increases when amiodarone or verapamil is co-administered with high doses of Simvastatin.

Diltiazem: the risk of developing myopathy is slightly increased in patients receiving diltiazem concomitantly with Simvastatin at a dose of 80 mg.

Simvastatin potentiates the effect of oral anticoagulants (for example, fenprocumone, warfarin) and increases the risk of bleeding, which requires the need to monitor blood clotting parameters before starting treatment, as well as quite often during the initial period of therapy. As soon as a stable level of prothrombin time or International Normalized Ratio (INR) is reached, its further monitoring should be carried out at the intervals recommended for patients receiving anticoagulant therapy. If you change the dosage or stop taking Simvastatin, you should also monitor prothrombin time or INR according to the above scheme.

Simvastatin therapy does not cause changes in prothrombin time and the risk of bleeding in patients who do not take anticoagulants.

Increases the level of digoxin in the blood plasma.

Colestyramine and colestipol reduce bioavailability (the use of Simvastatin is possible 4 hours after taking these drugs, while an additive effect is noted).

Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentration of agents metabolized by CYP3A4. The increase in the activity of HMG-CoA reductase inhibitors after consuming 250 ml of juice per day is minimal and has no clinical significance. However, consumption of a large volume of juice (more than 1 liter per day) while taking Simvastatin significantly increases the level of inhibitory activity against HMG-CoA reductase in blood plasma. In this regard, it is necessary to avoid consuming grapefruit juice in large quantities.

Overdose

No specific symptoms were detected in any of the several known cases of overdose (the maximum dose taken is 450 mg).

Treatment: induce vomiting, take activated charcoal, and perform symptomatic therapy. Liver and kidney functions should be monitored, as well as the level of CPK in the blood serum.

If you develop myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), you should immediately stop taking the drug and give the patient a diuretic and sodium bicarbonate (intravenous infusion). If necessary, hemodialysis is indicated.

Rhabdomyolysis can cause hyperkalemia, which can be eliminated by intravenous use of calcium chloride or calcium gluconate, glucose infusion with insulin, the use of potassium ion-exchange sorbents, or, in severe cases, by hemodialysis.

Description

Round biconvex tablets, film-coated from brown to light brown with a pinkish tinge of color.

Functional features

The absorption of Simvastatin is high. After oral use, the maximum plasma concentration is reached in approximately 1.3-2.4 hours and decreases by 90% after 12 hours. The binding to plasma proteins is about 95%.

It is metabolized in the liver, has a “first pass” effect through the liver (hydrolyzed to form an active derivative: beta-hydroxy acids, other active and inactive metabolites are also found). The half-life of active metabolites is 1.9 hours.

It is mainly excreted in the feces (60%) in the form of metabolites. About 10-15% is excreted by the kidneys in an inactive form.

Special instructions

At the beginning of Simvastatin therapy, a transient increase in the level of “liver” enzymes is possible.

Before starting therapy and then regularly conduct a liver function study (monitor the activity of” liver ” enzymes every 6 weeks for the first 3 months, then every 8 weeks for the remaining first year, and then once every six months), as well as when increasing doses, a liver function test should be performed. If the dose is increased to 80 mg, the test should be performed every 3 months. If there is a persistent increase in transaminase activity (3 times higher than the baseline level), Simvastatin should be discontinued.

Simvastatin, like 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, hypotension, planned major surgery, injuries, severe metabolic disorders).

Withdrawal of lipid-lowering drugs during pregnancy does not significantly affect the results of long-term treatment of primary hypercholesterolemia.

In patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome), if cholesterol levels are elevated, the underlying disease should be treated first.

Simvastatin should be used with caution in people who abuse alcohol and/or have a history of liver disease.

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

Concomitant use of grapefruit juice may increase the severity of side effects associated with taking Simvastatin, so they should be avoided simultaneously.

Simvastatin is not indicated in cases where there is hypertriglyceridemia of types I, IV and V.

Treatment with Simvastatin may cause myopathy leading to rhabdomyolysis and renal failure. The risk of this pathology increases in patients receiving one or more of the following medications simultaneously with Simvastatin: fibrates (gemfibrozil, fenofibrate), cyclosporine, nefazadone, macrolides (erythromycin, clarithromycin), antifungal agents from the azole group (ketoconazole, itraconazole) and HIV protease inhibitors (ritonavir). The risk of developing myopathy is also increased in patients with severe renal insufficiency.

All patients starting Simvastatin therapy, as well as patients who need to increase the dose of the drug, should be warned about the possibility of myopathy and the need to immediately consult a doctor in case of unexplained pain, muscle soreness, lethargy or muscle weakness, especially if this is accompanied by malaise or fever. Therapy with the drug should be stopped immediately if myopathy is diagnosed or suspected.

In order to diagnose the development of myopathy, it is recommended to regularly measure the CPK value.

When treated with Simvastatin, an increase in serum CPK may occur, which should be taken into account in the differential diagnosis of sternal pain. The criterion for drug withdrawal is an increase in the content of CPK in the blood serum by more than 10 times relative to the upper limits of the norm. In patients with myalgia, myasthenia gravis and/or a marked increase in CPK activity, treatment with the drug is discontinued.

The drug 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 for the next dose, do not double the dose.

Patients with severe renal insufficiency are treated under the control of renal function.

The duration of use of the drug is determined by the attending physician individually.

Influence on the ability to drive a car and work with mechanisms

No adverse effects of the drug on the ability to drive a car or work with mechanisms have been reported.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25°C.

Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Simvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets