Simvastatin Alkaloid - instructions for use, dose, side effects, contraindications

Tablets 10 mg: ascorbic acid 2,500 mg; citric acid monohydrate 1,250 mg; butyl hydroxy toluene 0.020 mg; cellulose microcrystalline 15,000 mg; lactose monohydrate 64.630 mg; pregelatinized starch 15,000 mg; Povidone 1,100 mg; magnesium stearate 0.500 mg.

Tablets of 20 mg: ascorbic acid 5,000 mg; citric acid monohydrate 2,500 mg; butyl hydroxy toluene 0.040 mg; cellulose microcrystalline 30,000 mg; lactose monohydrate 129.260 mg; pregelatinized starch 30,000 mg; Povidone 2,200 mg; magnesium stearate 1, 000 mg.

Tablets 40 mg: ascorbic acid 5,000 mg; citric acid monohydrate 2,500 mg; butyl hydroxy toluene 0.080 mg; cellulose microcrystalline 60,000 mg; lactose monohydrate 258.520 mg; pregelatinized starch 60,000 mg; Povidone 4,400 mg; magnesium stearate 2,000 mg.

Sheath: opadrai II pink 5,000 mg (for tablets 10 mg and 20 mg) or 10,000 mg (for tablets 40 mg) [polyvinyl alcohol, partially hydrolyzed; titanium dioxide; talc; macrogol-3000; iron dye oxide red [pigment 30] [E 172]; dye iron oxide yellow [pigment 10] [E 172]].

Description:

Grayish-pink, round, biconvex tablets, film-coated with a risk on one side.

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 the fermentation product of 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 alkaloid 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 (TG), low density lipoproteins (LINI), very low density lipoproteins (VLDL) and total cholesterol (in cases of heterozygous familial and non-family forms of hypercholesterolemia, with 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. L

Pharmacokinetics:

Suction

After oral administration simvastatin absorbed from the gastrointestinal tract (GIT) - about 61-85% _i and enters the systemic circulation. The maximum therapeutic concentration in blood plasma is achieved after 1.3-2.4 hours and decreases by 90% after 12 hours. Simultaneous food intake does not affect the absorption of simvastatin.

Distribution

Binding to plasma proteins is about 98%.

Metabolism

Simvastatin undergoes the effect of "first passage" through the liver (mainly hydrolysed to its active form beta hydroxy acid).

The concentration of the active metabolite of simvastatin in the systemic circulation is 5% of the ingested dose.

Excretion

Simvastatin excreted with bile. The half-life of active metabolites is 1.9 hours. It is excreted predominantly through the intestine (about 60%) in the form of metabolites. About 10-15% is excreted by the kidneys in an inactive form.

Indications:

Indications for use

Primary hypercholesterolemia Pa and Ib type with ineffectiveness of diet with low cholesterol and other non-pharmacological activities

(physical activity and weight loss) in patients with an increased risk of coronary atherosclerosis)

Combined hypercholesterolemia and hypertriglyceridemia; hyperlipoproteinemia, which can not be corrected by special diet and exercise

Homozygous hereditary hypercholesterolemia (as an adjunct to hypolipidemic therapy)

Ischemic heart disease (secondary prevention):

the drug is indicated to patients: to reduce overall mortality; with the aim of reducing the risk of coronary mortality and preventing myocardial infarction; with the aim of reducing the risk of stroke and transient cerebral circulatory disorders; with the purpose of slowing the progression of coronary atherosclerosis.

Contraindications:

If you have one of the listed diseases, before taking the drug must be consulted with your doctor.

- Increased sensitivity to the drug (to any of the components of the drug), as well as to other drugs of the statin series (inhibitors of HMG-CoA reductase) in history;

- diseases liver in the active phase,

persistent increase in activity of "hepatic" enzymes of unknown etiology;

- diseases skeletal musculature (myopathy);

- pregnancy and the period of breastfeeding;

- simultaneous use with strong inhibitors of the isoenzyme CYP3A4 (itraconazole, voriconazole, ketoconazole, posaconazole, HIV protease inhibitors, boceprevirov, telaprevir, erythromycin, clarithromycin, telithromycin and nefazodone, preparations containing the co-bicystate);

- concomitant treatment with gemfibrozil, cyclosporin or danazol;

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

- Pediatric use In children and adolescents under the age of 18 years, the safety and efficacy of Simvastatin Alkaloide have not been established.

Carefully:

With caution: appoint patients who abuse alcohol, patients after organ transplantation, who are being treated with immunosuppressants (due to an increased risk of rhabdomyolysis and kidney failure); at conditions that can lead to the development of severe renal failure, such as arterial hypotension, acute infectious diseases of severe course, severe metabolic and endocrine disorders, disturbances of water electrolyte balance,surgical interventions (including dental)

Pregnancy and lactation:

Simvastatin Alkaloid 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 plays an important role in fetal development, including synthesis of steroids and cell membranes, simvastatin alkaloid may have adverse effects on the fetus in the appointment of his pregnant ( women of reproductive age should avoid conception). If during pregnancy pregnancy occurs, the drug should be canceled, and the woman is warned about possible danger to the fetus.

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

Use of simvastatin An alkaloid is not recommended in women of childbearing age who do not use contraceptives.

Data on the isolation of simvastatin with mother's milk are absent. If necessary, simvastatin Alkaloid destination for women during lactation should be borne in mind that many drugs are excreted in breast milk,and there is a threat of severe reactions, so breastfeeding during admission not recommended

Dosing and Administration:

Before and during the treatment with Simvastatin, an alkaloid patient must follow a hypocholesterol diet to lower cholesterol.

Simvastatin Alkaloid should be applied 1 time per day in the evening, with plenty of water. The time of taking the drug should not be associated with eating. Hypercholesterolemia:

The recommended initial dose is 5 mg 1 time / day (14 tablets of 10 mg), with severe hypercholesterolemia - 10 mg per day.

Correction of the dosing regimen can be done at intervals of 4 weeks. The maximum daily dose is 80 mg.

With homozygous familial hypercholesterolemia, the dose of Simvastatin is 40 mg / day in the evening or 80 mg / day, divided into 3 doses - the first - 20 mg, the second - 20 mg and 40 mg in the evening. Ischemic heart disease (CHD):

In CHD Simvastatin alkaloid is prescribed in an initial dose of 20 mg 1 time / day in the evening; if necessary, the dose is gradually increased every 4 weeks to 40 mg.

In elderly patients and in patients with mild or moderate degree of renal failure, dosage changes are not required.

In patients with chronic renal failure (creatinine clearance less than 30 ml / min) or receiving reducing nicotinic acid in the lipid (> 1 g / day) in combination with Simvastatin alkaloid, the maximum recommended dose of simvastatin alkaloid should not exceed 10 mg per day.

For patients taking the preparation Simvastatin Alkaloid concomitantly with preparations of verapamil, diltiazem and fibrates other than gemfibrozil (see the section "Contraindications") or fenofibrate, the maximum recommended dose of Simvastatin Alkaloid is 10 mg per day.

For patients receiving amiodarone, amlopidine or ranolazine Simvastatin alkaloid, dose preparation Simvastatin Alkaloid should not exceed 20 mg per day.

For patients taking Simvastatin Alkaloid simultaneously with dronedarone, the maximum daily dose of simvastatin should not exceed 10 mg.

Side effects:

Side effect

There are reports of the possibility of developing the following adverse events (rare:> 0.01% and <0.1%; very rare: <0.01%; frequency ns set: it is impossible to estimate the frequency based on available data):

On the part of the organs of hemopoiesis Rare: anemia.

On the part of the skin Rare: skin rash, itching, alopecia.

On the part of the digestive system Rare: constipation, abdominal pain, flatulence, indigestion, diarrhea, nausea, vomiting, pancreatitis, hepatitis, cholestatic jaundice. Very rare: a fatal and non-fatal hepatic unit i shostatelnost.

From the central nervous system and sense organs

Rare: headache, dizziness, peripheral neuropathy, paresthesia.

Very rare: insomnia, memory impairment. The frequency is not established: depression, indistinctness of visual perception, violation of taste sensations.

From the side of the musculoskeletal system Rare: myopathy, myalgia, muscle cramps, rhabdomyolysis with acute renal failure (due to rhabdomyolysis) or without.

The frequency is not established: tendonopathy,

possibly with a rupture of tendons; myasthenia gravis.

On the part of the respiratory system

Frequency not established: interstitial

lung disease (especially with prolonged

application).

From the side of the reproductive system The frequency ns is fixed: erectile dysfunction.

General disorders and disorders in place

introduction of

Rare: asthenia.

Allergic and immunopathological reactions

Rarely developed hypersensitivity syndrome which manifested angioedema, lupus syndrome, rheumatic iolimialgiey, dermatomyositis, vasculitis, thrombocytopenia, eozino- filiey, erythrocytes increase comrade sedimentation rate (ESR), arthritis, arthralgia, rash, photosensitivity, fever, "Tide" of blood to skin of the face, shortness of breath and general weakness.

Very rare reports were received on the development of immuno-mediated necrotizing myopathy due to the use of statins.

Laboratory displays and Rare: increased activity of "liver" transaminases, alkaline phosphatase and gamma - glutamyltranspeptidase, krsatinphosphokinase (CK).

An increase in the concentration of glycosylated hemoglobin and fasting blood glucose in the fasting serum for statins, including simvastatin.

Other

The frequency is not set: palpitation.

Rare reports of cognitive impairment have been received (for example, various memory disorders: forgetfulness, memory loss, amnesia, confusion) associated with the use of statins.The following adverse events have been reported with some statins: sleep disorders, including insomnia and nightmarish dreams, sexual dysfunction, gynecomastia.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

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

Treatment: induce vomiting, take Activated carbon. 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), stop taking the medication immediately and administer the patient diuretic and sodium hydrogen carbonate (intravenous infusion). 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, potassium ion exchangers or, in severe cases, hemodialysis.

Interaction:

Interaction with other medicinal products

Contraindicated combinations: Strong inhibitors of the CYP3A4 isoenzyme increase the risk of myopathy by decreasing the rate of simvastatin clearance. Simultaneous use of strong inhibitors of the isoenzyme CYP3A4 (for example, itraconazole, voriconazole, ketoconazole, posaconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin and nefazodone, drugs containing co-cystitis) and simvastatin is contraindicated (see "Contraindications ").

Cytostatics, immunosuppressants: increase the risk of myopathy. Gemfibrozil, cycloschorin or danazol: since the risk of developing myopathy / rhabdomyolysis increases with co-administration with high doses of simvastatin, concomitant use is contraindicated (see section "Contraindications"),

Other fibrates: the risk of developing myopathy increases with the simultaneous use of simvastatin with gemfibrozil and other fibrates (except fsnofibrate). These hypolipidemic agents can cause myopathy under conditions of monotherapy. With the simultaneous use of simvastatin with fenofibrate, the risk of developing myopathy did not exceed the amount of risk associated with monotherapy with each drug. A nicotinic acid in lipid-lowering doses (more than 1 g / day): with the simultaneous use of simvastatin and nicotinic acid in lipid-lowering doses (more than 1 g / day), cases of myopathy / rhabdomyolysis have been described.

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

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

Simvastatin potentiates the action of peroral anticoagulants (eg fenprokumone, warfarin) and increases the risk of bleeding, which requires the need to monitor the coagulability of the blood before the treatment, and often enough in the initial period of therapy. Once a stable prothrombin time indicator or International Normalized Ratio (MPO) 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 nc causes changes in prothrombin time and the risk of bleeding in patients not taking anticoagulants.

Increases the concentration of digoxin in the blood plasma.

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

Fusidic acid: with simultaneous application of fusidic acid and simvastatin, the risk of myopathy may increase. Kolkhitsin: there were reports of myopathy and rhabdomyolysis with simultaneous administration of colchicine and simvastatin in patients with renal insufficiency. When combined therapy with these drugs, such patients should be carefully monitored.

Grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme and can increase the concentration in the blood plasma of agents metabolized by the CYP3A4 isoenzyme. The increase in the activity of HMG-CoA reductase inhibitors after consuming 250 ml of juice per day is minimal and ns is of clinical significance. However, the consumption of a large amount of juice (more than 1 liter per day) with the intake of simvastatin significantlyincreases 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.

Vorikopolazol: simultaneous use is contraindicated.

Droedaron: with simultaneous use increases the risk of myopathy and rhabdomyolysis. Moderate inhibitors of the isoenzyme CYP3A4: with the simultaneous use of drugs with moderate inhibitory activity against the isoenzyme CYP3A4 and simvastatin, especially at higher doses, the risk of myopathy may increase.

Special instructions:

At the beginning of Simvastatin therapy, an alkaloid may be a transient increase in the activity of "liver" enzymes.

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 "hepatic" transaminases (3-fold compared with the baseline level), the reception of Simvastatin Alkaloid should be discontinued.Simvastatin Alkaloid, like other inhibitors of HMG-Co-A-reductase, should not be used at an increased risk of rhabdomyolysis and renal insufficiency (against severe acute infection, arterial hypotension, planned large surgery, trauma, severe metabolic disorders).

In patients with a reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome), when the level of cholesterol is increased, the underlying disease should first be treated. Simvastatin Alkaloid is prescribed with caution 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 taking simvastatin alkaloid, therefore, they should be avoided at the same time. Simvastatin Alkaloid ire is indicated in cases where there is hyperglyceridemia I, IV and V types.

Treatment with simvastatin alkaloid can cause myopathy, leading to rhabdomyolysis and kidney failure.The risk of this pathology increases in patients receiving simultaneously with Simvastatin alkaloid one or more of the following drugs: fibrates (gemfibrozil, fenofibrate), cyclosporine, nefazodone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of "azoles" (ketoconazole, itraconazole), drugs containing the co-bicystate and HIV protease inhibitors (ritonavir). The risk of myopathy is also increased in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min). All patients starting therapy with simvastatin alkaloid, 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 to regularly evaluate the activity of CK.

In the treatment of simvastatin alkaloid, an increase in the activity of 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 the activity of CK in the blood serum more than 10 times the upper limit of the norm. In patients with myalgia, myasthenia gravis and / or marked increase in the activity of CKK, treatment with the drug is stopped.

The risk of developing myopathy can be increased because of the simultaneous use of fusidic acid with statins, including simvastatin. Single cases of rhabdomyolysis with simvastatin have been reported. A temporary suspension of treatment with simvastatin may be considered. If such treatment is necessary, for the condition of patients taking fusidic acid and simvastatin, it is necessary to closely monitor.

Risk of development of myopathy / rhabdomyolysis The risk of myopathy and rhabdomyolysis increases with simultaneous use with dronedarone and other drugs (see section "Interaction with Other Drugs").

The drug is effective both in monotherapy, and in combination with ssquestrant bile acids.

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.

Patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) are treated under the control of kidney function. Duration of the drug is determined individually by the attending physician.

Form release / dosage:

Tablets, film-coated, 10 mg, 20 mg and 40 mg.

Tablets 10 mg

For 7 tablets in a blister of aluminum foil and transparent three-layer film (PVC / TE / PVDC). For 4 blisters (28 tablets), together with the instructions for use are placed in a cardboard box.

Tablets of 20 mg and 40 mg

For 14 tablets in a blister of aluminum foil and transparent three-layer film (PVC / TE / PVDC). For 2 blisters (28 tablets), together with the instructions for use are placed in a cardboard box.

Packaging:

Tablets, film-coated, 10 mg, 20 mg and 40 mg.

Tablets 10 mg

For 7 tablets in a blister of aluminum foil and transparent three-layer film (PVC / TE / PVDC). For 4 blisters (28 tablets), together with the instructions for use are placed in a cardboard box.

Tablets of 20 mg and 40 mg

For 14 tablets in a blister of aluminum foil and transparent three-layer film (PVC / TE / PVDC). For 2 blisters (28 tablets), together with the instructions for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of 15 to 25 C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004964/09

Date of registration:24.06.2009

The owner of the registration certificate:Alkaloid, JSCAlkaloid, JSC Macedonia

Manufacturer: & nbsp

ALKALOID, AD Macedonia

Information update date: & nbsp30.07.2015

Illustrated instructions

Instructions

Simvastatin Alkaloid (Simvastatin Alkaloid)