Simvastatin pills 10mg №30

Instruction

(information for specialists)

on medical use of the drug

Simvastatin

(Simvastatin)

Tradename: Simvastatin

International non-proprietary name: simvastatin

Dosage Form: film coated tablets

Composition

One pill film coated contains:

active substance: simvastatin - 10 mg or 20 mg;

Excipients: microcrystalline cellulose - 70.00 / 140.00 mg, lactose monohydrate (milk sugar) - 21.00 / 42.00 mg, pregelatinized starch (starch 1500) - 33.73 / 67.46 mg, colloidal silicon dioxide (aerosil ) - 0.75 / 1.50 mg, Ascorbic acid - 2.50 / 5.00 mg, butylhydroxyanisol - 0.02 / 0.04 mg, stearic acid - 1.25 / 2.50 mg, Magnesium stearate - 0, 75 / 1.50 mg, polyvinyl alcohol - 2.33 / 4.66 mg, macrogol (polyethylene glycol) - 1.18 / 2.36 mg, iron dye black oxide - 0.02 / 0.04 mg, talc - 0.86 / 1.72 mg, iron dye yellow oxide - 0.28 / 0.56 mg, iron dye red oxide - 0.19 / 0.38 mg, titanium dioxide - 0.97 / 1.94 mg.

Description:

round biconvex tablets, film-coated from brown to light brown with a pinkish tinge.

Pharmacotherapeutic group:

hypolipidemic agent, HMG-CoA reductase inhibitor.

Pharmacological properties

Pharmacodynamics:

The lipid-lowering agent, obtained synthetically from the fermentation product Aspergillus terreus, is an inactive lactone, 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 to form mevalonate from HMG-CoA. Since the transformation of HMG-CoA into mevalonate is an early stage in the synthesis of cholesterol, the use of Simvastatin does not cause the accumulation of potentially toxic sterols in the body. HMG-CoA is easily metabolized to acetyl-CoA, which is involved in many processes of synthesis in the body.

It 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-familial forms of hypercholesterolemia, with mixed hyperlipidemia, when elevated cholesterol is a part of the disease, the factor of hypercholesterolemia, with mixed hyperlipidemia, when the high content of cholesterol is a part of the disease, is one of the most important factors in hypercholesterolemia, with mixed hyperlipidemia, when high content of cholesterol is a factor..

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

The beginning of the manifestation of the effect - after 2 weeks from the start of the reception, the maximum therapeutic effect is achieved after 4-6 weeks. The effect persists with continued treatment, with the cessation of therapy, the content of cholesterol gradually returns to its original level.

Pharmacokinetics:

Simvastatin absorption is high. After ingestion, the maximum plasma concentration is reached after about 1.3-2.4 hours and decreases by 90% after 12 hours. Communication with proteins of a blood plasma makes about 95%.

Metabolized in the liver, has the effect of "first pass" through the liver (hydrolyzes to form an active derivative: beta-hydroxy acids, other active, as well as inactive metabolites are found). The half-life of active metabolites is 1.9 hours.

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

Indications for use

Hypercholesterolemia:

• Primary hypercholesterolemia (type IIa and IIb) with the ineffectiveness of diet therapy with low cholesterol and other non-drug interventions (exercise 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, reduce the risk of cardiovascular disorders (stroke or transient ischemic attacks), slow the progression of coronary atherosclerosis, reduce the risk of revascularization procedures.

Contraindications

• Hypersensitivity to simvastatin or to other components of the drug (including hereditary lactose intolerance), as well as to other statin 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).

Carefully prescribed to patients with alcohol abuse, patients after organ transplantation, which is treated with immunosuppressants (due to the increased risk of rhabdomyolysis and renal failure); in conditions that can lead to the development of severe kidney function deficiency, such as arterial hypotension, acute severe infectious diseases, pronounced metabolic and endocrine disorders, disturbances of water and electrolyte balance, surgical interventions (including dental) or injuries; patients with reduced or elevated skeletal muscle tone of unknown etiology; epilepsy.

Pregnancy and lactation period

Simvastatin may have an adverse effect on the fetus and is contraindicated in pregnant women. There are several reports of the development of anomalies in newborns whose mothers took simvastatin.

Women of reproductive age who take simvastatin should avoid conception. The use of Simvastatin is not recommended for women of childbearing age who do not use contraceptives. If, in the course of treatment, the pregnancy nevertheless occurs, Simvastatin should be canceled and the woman should be warned of the possible danger to the fetus.

Data on the allocation of Simvastatin with breast milk are not available.If necessary, the appointment of Simvastatin during lactation should take into account that many drugs are excreted in breast milk, and there is a risk of severe reactions, so breastfeeding while taking the drug is not recommended.

Dosage and administration

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

Simvastatin should be taken orally once a day in the evening, drinking plenty of water.

Drug intake time should not be associated with food intake.

The recommended dose of simvastatin for treatment 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) 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 daily 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).

When treating patients with ischemic heart disease (CHD) or high risk of developing CHD effective doses of simvastatin are 20-40 mg per day. Therefore, the recommended initial dose in such patients is 20 mg per day.Changes (selection) dose should be carried out at intervals of 4 weeks, if necessary, the dose can be increased to 40 mg per day. If the content of LDL is less than 75 mg / dl (1.94 mmol / l), 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 moderately severe degree of renal insufficiency, changes in the dosage of the drug are not required.

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

For patients taking Amiodarone or Verapamil simultaneously with simvastatin, the daily dose should not exceed 20 mg.

Side effect

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

From the nervous system and sensory organs: asthenic syndrome, headache, dizziness, insomnia, muscle cramps, paresthesia, peripheral neuropathy, blurred vision, impaired taste sensations.

From the musculoskeletal system: myopathy, myalgia, muscle cramps, weakness; rarely - rhabdomyolysis.

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

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

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

Overdose

None of the known several cases of overdose (maximum dose of 450 mg) revealed any specific symptoms.

Treatment: induce vomiting, take activated charcoal, conduct symptomatic therapy. Liver and kidney function, serum CK levels should be monitored.

With the development of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect), the drug should be stopped immediately and a diuretic and sodium bicarbonate should be given to the patient (intravenous infusion). If necessary, hemodialysis is indicated.

Rhabdomyolysis can cause hyperkalemia, which can be eliminated by intravenous administration of Calcium chloride or Calcium gluconate, infusion of glucose with insulin, using potassium ion exchange sorbents or, in severe cases, by hemodialysis.

Interaction with other drugs

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 myopathy / rhabdomyolysis increases with co-administration of cyclosporine or danazol with high doses of simvastatin.

Other hypolipidemic drugs that can cause the development of myopathy: the risk of myopathy increases with the joint appointment of other lipid-lowering drugs that are not potent inhibitors of CYP3A4, but can cause myopathy in monotherapy. Such as gemfibrozil and other fibrates (except fenofibrate), as well as nicotinic acid in a dose of ≥ 1 g per day.

Amiodarone and verapamil: the risk of myopathy is increased when co-administering amiodarone or verapamil with high doses of simvastatin.

Diltiazem: the risk of myopathy slightly increases in patients receiving diltiazem simultaneously with Simvastatin at a dose of 80 mg.

Simvastatin potentiates the action of oral anticoagulants (for example, fenprokumon, warfarin) and increases the risk of bleeding, which requires the need to monitor blood clotting before treatment, and often enough in the initial period of therapy. Once a stable level of prothrombin time or the International Normalized Relationship (INR) is achieved, its further monitoring should be carried out at intervals recommended for patients receiving anticoagulant therapy. When changing the dosage or discontinuation of Simvastatin, the prothrombin time or INR should also be monitored as described above.

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

Increases the level of Digoxin in the blood plasma.

Kolestyramine and Kolestipol reduce bioavailability (use of Simvastatin is possible 4 hours after taking these medicines, with an additive effect).

Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentration of drugs metabolized by CYP3A4. Increasing the activity of HMG-CoA reductase inhibitors after consuming 250 ml of juice per day is minimal and has no clinical significance. However, consuming 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 plasma. In this regard, it is necessary to avoid the consumption of grapefruit juice in large quantities.

special instructions

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

Before starting therapy and continue to conduct regular liver function tests (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 with increasing doses liver function tests should be performed. If you increase the dose to 80 mg, you need to test every 3 months.With a persistent increase in the activity of transaminases (3 times compared with the initial level), the administration of Simvastatin should be stopped.

Simvastatin, like other inhibitors of HMG-CoA reductase, should not be used with an increased risk of developing rhabdomyolysis and renal failure (against the background of severe acute infection, hypotension, planned major surgery, trauma, severe metabolic disorders).

Cancellation of hypolipidemic drugs during pregnancy does not have a significant impact on 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), with an increase in cholesterol level, the therapy underlying the disease should first be carried out.

Simvastatin is prescribed 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 cholesterol diet.

The simultaneous intake of grapefruit juice can increase the severity of side effects associated with the intake of simvastatin, so their simultaneous intake should be avoided.

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

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

All patients who start therapy with Simvastatin, as well as patients who need to increase the dose of the drug, should be warned about the possibility of myopathy and the need for immediate treatment to the doctor in case of unexplained pain, muscle pain, lethargy or muscle weakness, especially if this is accompanied by indisposition or fever. Drug therapy should be immediately discontinued if myopathy is diagnosed or contemplated.

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

When treating with Simvastatin, an increase in the serum CPK content is possible, which should be taken into account in the differential diagnosis of chest pain. The criterion for discontinuation of the drug is an increase in the content of CK in the serum of more than 10 times relative to the upper limits of the norm. In patients with myalgia, myasthenia and / or a pronounced increase in the activity of CPK, treatment with the drug is stopped.

The drug is effective both in the form of monotherapy, and in combination with bile acid sequestrants.

In case of missing the current dose, the drug should be taken as soon as possible. If the time for the next dose has arrived, do not double the dose.

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

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

Influence on ability of driving and work with mechanisms

No adverse effects of the drug on the ability to drive and work with mechanisms were reported.

Release form

Film-coated pills of 10 mg and 20 mg.

On 10 pills in a blister strip packaging from the PVC film and aluminum printed lacquer foil.

1, 2, 3, 4 or 5 blisters with instructions in a pack of cardboard.

Storage conditions

In a dry, dark place at a temperature not higher than 25 ° C.

Keep out of the reach of children.