Holvasim - instructions for use, doses, side effects, contraindications

core: microcrystalline cellulose, lactose monohydrate, hypromellose, silicon dioxide colloid, citric acid, sodium carboxymethyl starch, povidone, sodium lauryl sulfate, magnesium stearate, ascorbic acid, butylhydroxytoluene; film sheath: opadrai pink 03B44038 (hypromellose 2910, titanium dioxide, macrogol, iron oxide dye, dye red charming speaker, dye yellow-and-yellow).

Description:

Biconvex tablets are oval, from pink to orange, covered with a film shell, with a risk and engraving S / P on the one hand and with engraving S40 without risks on the other hand.

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 (TG), low-density lipoproteins (LDL), 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 of high density lipoprotein (HDL) 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 plasma concentration is reached after approximately 1.3-2.4 hours, and reduced by 90% after 12 h. The connection to plasma proteins is approximately 95 %.

Metabolized in the liver, has the effect of a "first pass" through the liver (hydrolyzed to form an active derivative: beta-hydroxycin slots,

other active as well as inactive metabolites were found). The half-life of active metabolites is 1.9 hours.

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

Indications:

The primary hypercholesterolemia (heterozygous familial and non-family, and types IIb and Pa mixed) with poor diet 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 (type IV, as a supplement to diet), disbetalipoproteinemia (type III, in cases of inadequate diet therapy), mixed forms;

diseases of the cardiovascular system (including asymptomatic ischemic heart disease) - for prevention with a view to reducing the overall risk of death, myocardial infarction (to slow the progression of coronary atherosclerosis), stroke and transient disorders of cerebral circulation.

Contraindications:

increased sensitivity to simvastatin or to other components of the drug (including hereditary lactose intolerance), as well as to other statin drugs (inhibitors of HMG-CoA reductase) in the anamnesis;
liver disease in the active phase, persistent increase in the activity of "liver" transaminases of unclear etiology;
pregnancy;
lactation period.

Carefully:

Alcoholism, liver disease in the anamnesis;
conditions with a high risk of secondary renal failure and rhabdomyolysis - severe electrolyte imbalance, endocrine and metabolic disorders, arterial hypotension, severe acute infections, myopathy, uncontrolled convulsions, extensive surgical interventions, trauma, conditions after organ transplantation with immunosuppressive therapy;
age to 18 years (efficacy and safety not studied).

Pregnancy and lactation:

Holvasim is contraindicated in pregnancy. There are several reports of the development of anomalies in newborns whose mothers were taking simvastatin.

Women of childbearing age who receive simvastatin, should avoid conception. If during the treatment the pregnancy does come, Holvasim should be canceled, and the woman should be 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 Holvasima during breastfeeding, it should be borne in mind that many drugs are excreted in breast milk and there is a threat of severe reactions, so breast-feeding during taking the drug is not recommended.

Dosing and Administration:

Before the start of treatment with Holvasim, the patient should be prescribed a standard hypocholesterol diet, which should be observed throughout the course of treatment. Holvasim should be taken orally 1 time per day in the evening, with plenty of water.

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

The recommended dose of Holvasima 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. 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 Holvasima 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 developing CHD, effective dose of Holvasima is 20-40 mg per day. Therefore, the recommended initial 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), 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 degree of renal insufficiency, dosage changes are not required.

In patients with chronic renal failure (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 dosage of Holvasima should not exceed 10 mg per day.

For patients receiving amiodarone or verapamil At the same time as Holvasim, the daily dosage of Holvasim should not exceed 20 mg.

Side effects:

From the digestive system: constipation, diarrhea, loss of appetite, flatulence, nausea, abdominal pain, vomiting, cholestatic jaundice, pancreatitis, hepatitis, increased activity of "liver" enzymes, alkaline phosphatase and creatine phosphokinase (CKF).

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

From the cardiovascular system: possible transient arterial hypotension.

From the musculoskeletal system: possible myalgia, rhabdomyolysis, increased activity of CK; in rare cases - myopathy.

Allergic reactions: rarely - angioedema, lupus-like syndrome, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis, urticaria, fever, dyspnea.

Dermatological reactions: photosensitivity, skin rash, itching, skin hyperemia, alopecia.

Other: rheumatic polymyalgia, anemia, in rare cases - myopathy, decreased potency.

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) should immediately stop taking the drug and inject the patient with a 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:

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 dsazole: 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 capable of causing myopathy under conditions of monotherapy.Such as gemfibrozil and other fibrates (except fenofibrate), as well as a nicotinic acid in a dose> 1 g per day. Amiodarone and verapamt: The risk of myopathy increases with the joint administration of amiodarone or verapamil with high doses of simvastatin.

Diltiazem: 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 the need to monitor the coagulability of the blood 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 who do not take anticoagulants.

Increases the level digoxin in the blood plasma. about

Kolestyramine and colestipol reduce 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. 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 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 therapy with Holvasim, a transient increase in the level of "hepatic" enzymes is possible.

Before the start of therapy and further regularly carry out a study of the function of baking (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 test should be performed to determine the function of the liver. When the dose is raised to 80 mg, a test should be performed every 3 months. With a persistent increase in the activity of transaminases (3-fold compared with the baseline level), Holvasim should be discontinued.

Holvasim, like other inhibitors of HMG-Co-A reductase inhibitors, should not be used at an increased risk of rhabdomyolysis and renal failure (on the background of severe acute infection, hypotension, planned major 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.

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 when prescribing it to pregnant women (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 use of HOLVASIM is not recommended in women of childbearing age who do not use contraceptives.

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

Before and during treatment, the patient should be on a hypocholesterol diet. Simultaneous intake of grapefruit juice can increase the severity of side effects associated with taking Holvasima, therefore, they should be avoided at the same time.

Holvasim is not indicated in cases where there is hypertriglyceridemia I, IV and V types. Treatment with Holvasim can cause myopathy, leading to rhabdomyolysis and kidney failure. The risk of this pathology increases in patients,who receive simultaneously with Holvasim one or more of the following medicines: fibrates (gemfibrozil, fenofibrate), ciclosporin, nefazodone, macrolides (erythromycin, clarithromycin, telithromycin), antifungal agents from the group of "azoles" (ketoconazole, intraconazole) HIV protease inhibitorsritonavir).

The risk of developing myopathy is also increased in patients with severe renal failure.

All patients starting therapy with Holvasim, 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.

With the treatment of Holvasim, it is possible to increase the content of serum CK, 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.

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 failure receive treatment under the control of kidney function.

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

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

On the adverse impact of the Holvasim on the ability to drive and work with machinery was not reported.

Form release / dosage:

Tablets coated with a film coating of 40 mg.

Packaging:

For 30 and 100 tablets in a sealed plastic bottle with a control of the first opening, containing a bag of silica gel (desiccant).

One bottle together with the Instruction for use is placed 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:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004410/08

Date of registration:07.06.2008

The owner of the registration certificate:Shin Pung Pharmaceutical Co., Ltd.Shin Pung Pharmaceutical Co., Ltd. The Republic of Korea

Manufacturer: & nbsp

SHIN POONG PHARMACEUTICAL, Co. Ltd. The Republic of Korea

Representation: & nbspPharmInform Ltd.PharmInform Ltd.Russia

Information update date: & nbsp01.08.2015

Illustrated instructions

Instructions

Holvasim (Cholvasim)