Sincard - instructions for use, dose, side effects, contraindications

One tablet, film-coated, contains active substance simvastatin 10 mg or 20 mg and Excipients: lactose, corn starch, microcrystalline cellulose, ascorbic acid, talc, butylhydroxytoluene, silicon dioxide colloid, magnesium stearate, and in the shell: (for tablets of 10 mg) hypromellose, titanium dioxide, talc, propylene glycol, iron dye oxide yellow; (for tablets of 20 mg) hypromellose, triacetin, talc, titanium dioxide and dye sunset yellow.

Description:

Round biconvex tablets coated with a film coat, light yellow (for 10 mg) and orange (for 20 mg) color.

Pharmacotherapeutic group:lipid-lowering agent - HMG-CoA reductase inhibitor

ATX: & nbsp

C.10.A.A Inhibitors of HMG-CoA reductase

C.10.A.A.01 Simvastatin

Pharmacodynamics:

A hypolipidemic agent obtained synthetically from a fermentation product Aspergillus terreus, is an inactive lactone in the body undergoes hydrolysis with the formation of 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 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 synthesis processes in the body.

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

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

The onset of the effect is 2 weeks after the start of the treatment, the maximum therapeutic effect is achieved after 4-6 weeks. The effect persists with the continuation of treatment, with the cessation of therapy, the cholesterol content gradually returns to the baseline level.

Pharmacokinetics:

Absorption of simvastatin is high. After oral administration, the maximum concentration in the blood plasma is reached after approximately 1.3 - 2.4 hours and decreases by 90% after 12 hours. The connection with plasma proteins is about 95%.

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

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

Indications:

Hypercholesterolemia:

Primary Hypercholesterolemia (type Pa and ub) with poor diet low in cholesterol and other non-drug interventions (exercise and weight reduction) in patients with an increased risk of coronary atherosclerosis;
combined hypercholesterolemia and hypertriglyceridemia, not corrected by special diet and exercise;
homozygous hereditary hypercholesterolemia (as an adjunct to hypolipidemic therapy);
secondary hyperlipidemia: hypercholesterolemia,

hypertriglyceridemia (IV type, as an adjunct to diet), disbetalipoproteinemiya (III type, in cases inadequate diet), as well as mixed forms);

Cardiac ischemia:

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 artery atherosclerosis, reduce the risk of revascularization procedures.

Contraindications:

hypersensitivity to simvastatin or other components of the drug;
increased sensitivity to other inhibitors of HMG-CoA reductase in the anamnesis;
liver disease in the active phase, persistent increase in the activity of "liver" enzymes of unclear etiology;
diseases of skeletal muscles (myopathy);
age under 18 years (effectiveness and safety not established);
hereditary lactose intolerance.

Carefully:

patients who abuse alcohol;
patients after organ transplantation who undergo immunosuppressant therapy (due to an increased risk of rhabdomyolysis and renal insufficiency);
at conditions that can lead to the development of severe renal failure, such as arterial hypotension, acute infectious diseases of severe course, pronounced metabolic and endocrine disorders, / destruction of the water-electrolyte balance,

surgical interventions (including dental) or trauma;

patients with decreased or increased tone of skeletal muscles of unknown etiology;
epilepsy.

Pregnancy and lactation:

Simvastatin is contraindicated in pregnancy.

Due to the fact that inhibitors of HMG-CoA reductase inhibitors inhibit the synthesis of cholesterol, and cholesterol and other products of its synthesis play an essential role in fetal development, including steroids and synthesis of cellular membranes, simvastatin may have an adverse effect on the fetus. There are several reports of the development of anomalies in newborns whose mothers were taking simvastatin. Therefore, women of reproductive age should avoid conception.

If during the treatment with simvastatin pregnancy does occur, the drug should be immediately canceled, and the woman is warned about the possible danger to the fetus.

Data on the isolation of simvastatin with mother's milk are absent. If it is necessary to appoint simvastatin during breastfeeding, it should be borne in mind that many drugs are excreted in breast milk and there is a threat of development of severe reactions, so breast-feeding during drug intake should be discontinued.

Dosing and Administration:

Before the start of Sincard's treatment, the patient should be prescribed a standard hypocholesterolemic diet, which must be observed throughout the course of treatment.

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

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

The recommended dose of Sincard for treatment hypercholesterolemia varies from 10 to 80 mg once a day in the evening. The recommended initial dose of the drug 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.

If the current dose is skipped, the drug should be taken as soon as possible. If it's time to take the next dose, do not double the dose.

In most patients, the optimal effect is achieved when taking the drug at doses up to 20 mg per day.

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

In the treatment of patients with ischemic heart disease (CHD) or a high risk of CHD effective dose of Sincard is 20-40 mg per day. Therefore, the recommended initial dose in such patients is 20 mg per day. The change (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), the total cholesterol content is less than 140 mg / dl (3.6 mmol / L), the dose of the drug should be reduced.

Have elderly patients and patients with mild to moderate renal failure no change in dosage is required.

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

For patients receiving amiodarone or verapamil Simultaneously with Sincard, the maximum daily dose of Sincard should not exceed 20 mg.

If the current dose is skipped, the drug should be taken as soon as possible. If it's time to take the next dose, do not double the dose.

Side effects:

From the digestive system:

possible abdominal pain, constipation,flatulence, nausea, diarrhea, pancreatitis, vomiting, gastralgia, hepatitis, cholestatic jaundice, increased activity of "liver" enzymes, alkaline phosphatase and creatine phosphokinase (CK).

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

Allergic and immunopathological reactions:

angioedema, rheumatic polymyalgia, vasculitis, thrombocytopenia, increased erythrocyte sedimentation rate (ESR), fever, arthritis, urticaria, photosensitivity, skin hyperemia, blood flushes to the face, dyspnea, lupus-like syndrome, eosinophilia.

Dermatological reactions:

rarely skin rash, itching, alopecia, dermatomyositis.

From the musculoskeletal system:

Myopathy, myalgia, muscle cramps, weakness; rarely rhabdomyolysis.

Other:

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

Overdose:

In none of the known few cases of overdose (the maximum dose of 450 mg) specific symptoms were identified.

Treatment: cause vomiting, take Activated carbon. Requires symptomatic therapy. It is necessary to monitor the liver and kidney function, the level of CK in the blood serum.

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

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

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 myopathy / rhabdomyolysis increases with the simultaneous administration of cyclosporine or danazol with high doses of simvastatin.

Other hypolipidemic agents that can cause the development of myopathy: the risk of myopathy increases with the co-administration of other lipid-lowering drugs that are not potent inhibitors CYP3A4, but are capable of inducing mocopathy under conditions of monotherapy. Such as

gemfibrozil and other fibrates (except fenofibrate), and a nicotinic acid in a dose of> 1 g per day.

Amiodarone and verapamil: The risk of myopathy increases with the joint administration of amiodarone or verapamil with high doses of simvastatin.

Dithiazem: The risk of myopathy is slightly increased in patients receiving diltiazem simultaneously with simvastatinom in a dose of 80 mg.

Simvastatin potentiates the action oral anticoagulants (eg fenprokumone, warfarin) and increases the risk of bleeding, which requires mandatory monitoring of coagulation rates before treatment, and often enough in the initial period of therapy. Once a stable prothrombin time indicator or International Normalized Ratio (MNO) is reached, its further control should be performed at intervals recommended for patients receiving anticoagulant therapy.When changing the dosage or stopping the intake of simvastatin, it is also necessary to monitor prothrombin time or INR according to the above scheme.

Therapy with simvastatin does not cause changes in prothrombin time and the risk of bleeding in patients not taking anticoagulants.

Increases the level digoxin in the blood plasma.

Kolestyramine and colestipol reduce the bioavailability (the use of simvastatin is possible 4 hours after the administration of these drugs, with an additive effect noted).

Grapefruit juice contains one or more ingredients that inhibit CYP3A4 and can increase the concentration in the blood plasma of metabolic agents CYP3A4. An 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 amount of juice (more than 1 liter per day) with the use of simvastatin significantly increases the level of inhibitory activity against HMG-CoA reductase in blood plasma. In this regard, it is necessary to avoid the consumption of grapefruit juice in large quantities.

Special instructions:

At the beginning of Sincard therapy, a transient increase in the level of "hepatic" enzymes is possible.

Before starting therapy, 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 remainder of the first year, and then once every six months), as well as with increasing doses a liver function test should be performed. When the dose is raised to 80 mg, a test should be performed every 3 months. With a persistent increase in the activity of enzymes (3-fold compared with the baseline level), Sincard should be discontinued.

Syncard, like other inhibitors of HMG-CoA reductase, should not be used with an increased risk of rhabdomyolysis and renal insufficiency (against severe acute infection, arterial hypotension, planned large surgery, trauma, severe metabolic disorders).

The abolition of lipid-lowering drugs during pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.

The use of Sincard is not recommended for women of childbearing age who do not use contraceptives.

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 disease.

Sincare is cautiously prescribed to people who abuse alcohol and / or have a history of liver disease.

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

Simultaneous reception of grapefruit juice can increase the severity of side effects associated with Sincard's administration, therefore, simultaneous administration should be avoided.

Syncard is not prescribed in cases of hypertriglyceridemia I, IV and V types.

Treatment with simvastatin can cause myopathy, leading to rhabdomyolysis and kidney failure. The risk of this pathology increases in patients receiving simultaneously with simvastatin one or more of the following drugs: fibrates (gemfibrozil, fenofibrate),

cyclosporine, nefazadone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of "azoles" (ketoconazole, intraconazole) and HIV protease inhibitors (ritonavir).The risk of developing myopathy is also increased in patients with severe renal failure.

All patients starting 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 to immediately seek medical attention in the event of unexplained pain, muscle soreness, lethargy or muscle weakness, especially if accompanied by malaise or fever. The drug should be discontinued immediately if myopathy is diagnosed or suspected.

In order to diagnose the development of myopathy, it is recommended that CK values be measured regularly.

In the treatment with simvastatin, an increase in serum CKF is possible, which should be taken into account in the differential diagnosis of chest pain. The criterion for the discontinuation of the drug is an increase in serum levels of CK in more than 10 times the upper limit of the norm. In patients with myalgia, myasthenia gravis and / or a marked increase in the activity of CKK, treatment with the drug is stopped.

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

Patients with severe renal failure receive treatment under the control of kidney function.

Duration of the drug is determined individually by the attending physician.

Effect on the ability to drive transp. cf. and fur:

The adverse effects of simvastatin on the ability to drive and work with machinery have not been reported.

Form release / dosage:

Tablets, film-coated, 10 mg and 20 mg.

For 10 tablets, film-coated, 10 and 20 mg per blister of Aluminum / Aluminum.

For 3 or 10 blisters together with instructions for use in a cardboard box.

Packaging:

For 10 tablets, film-coated, 10 and 20 mg per blister of Aluminum / Aluminum.

For 3 or 10 blisters together with instructions for use in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003522/09

Date of registration:13.05.2009

The owner of the registration certificate:Micro Labs LimitedMicro Labs Limited India

Manufacturer: & nbsp

MICRO LABS, Limited India

Information update date: & nbsp31/05/2015

Illustrated instructions

Instructions

Sinquard (Synkard)