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

Lactose monohydrate 47.6 mg / 95.6 mg / 190.0 mg / 286.0 mg / 381.0 mg; Microcrystalline cellulose 5.0 mg / 10.0 mg / 20.0 mg / 30.0 mg / 40.0 mg; Butyl hydroxy anisole 10.0 μg / 20.0 μg / 40.0 μg / 60.0 μg / 80.0 μg; Ascorbic acid 1.3 mg / 2.5 mg / 5.0 mg / 7.5 mg / 10.0 mg;

Citric acid monohydrate 0.63 mg / 1.3 mg / 2.5 mg / 3.8 mg / 5.0 mg; Magnesium stearate 0.5 mg / 1.0 mg / 2.0 mg / 3.0 mg / 4.0 mg;

Hypromellose 5 cps 0.35 mg / 0.7 mg / 1.5 mg / 2.0 mg / 3.0 mg;

Eipromellosis 15 cps 0.53 mg / 1.1 mg / 2.3 mg / 3.0 mg / 4.5 mg;

Talc 0.16 mg / 0.32 mg / 0.69 mg / 0.90 mg / 1.4 mg;

Titanium dioxide (E171) 0.40 mg / 0.80 mg / 1.7 mg / 2.3 mg / 3.4 mg Iron oxide red - / 4.3 μg / 26.0 μg / - / 0.14 mg Iron oxide yellow 4.3 μg / 1.7 μg / 0.11 μg / - / -

Description:

Tablets 5 mg:

Tablets of light yellow color, covered with a shell, oval, convex, with a notch on one side and indicating "SIM 5 "on the other, on a broken white color.

Tablets 10 mg:

Tablets of light pink color, covered with a shell, oval, convex, with a notch on one side and indicating "SIM 10 "on the other, on a broken white color.

Tablets of 20 mg:

Tablets of light orange color, covered with a shell, oval, convex, with a notch on one side and indicating "SIM 20 "on the other, on a broken white color.

Tablets 30 mg:

Tablets are white or almost white in color, covered with a shell, oval, convex, with a notch on one side and indicating "SIM 30 "on the other, on a broken white color.

Tablets 40 mg:

Tablets of pink color, covered with a shell, oval, convex, with a notch on one side and indicating "SIM 40 "on the other, on a broken white color.

Pharmacotherapeutic group:A hypolipidemic agent (inhibitor of 3-hydroxy-3-methyl-glutarylcoferment A-reductase (HMG-CoA reductase))

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 beta-hydroxy acid. The active metabolite inhibits 3-hydroxy-3-methyl-glutaryl-CoA- reductase (HMG-CoA reductase), an enzyme catalyzing 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 (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 concentration of triglycerides (TG), low density lipoproteins (L11NP), very low density lipoproteins (VLDL) and total cholesterol (OCS) (with heterozygous familial and non-family hypercholesterolemia, mixed hyperlipidemia, when the elevated concentration of cholesterol in the blood plasma is a risk factor). Increases the concentration of high density lipoproteins (HDL) and reduces the ratio of LDL / HDL and OXC / HDL in the blood plasma.

The onset of the effect is 2 weeks after the beginning of the application, the maximum therapeutic effect is achieved after 4-6 weeks of therapy. The effect persists with the continuation of treatment, with the cessation of therapy, the concentration of cholesterol in the blood plasma gradually returns to the initial value.

Pharmacokinetics:

Simvastatin well absorbed from the gastrointestinal tract. The intake of food does not affect the absorption of simvastatin. After oral administration, the maximum concentration in the blood plasma is reached after about 1-2 hours and decreases by 90% after 12 hours. Binding to plasma proteins is more than 95%. Do not cumulate.

Extensively metabolized in the liver (hydrolyzed with the formation of the main active derivative - beta-hydroxy acid and four other active metabolites). It is allocated mainly in the form of metabolites by the intestine (60%) for 4 days, 13% is excreted by the kidneys in an inactive form.

Patients with impaired renal function

Because the simvastatin is allocated by the kidney in a small amount, there is no need for dose adjustment in patients with moderate and moderate renal dysfunction.Nevertheless, in patients with severe renal dysfunction (creatinine clearance (CK) less than 30 ml / min) simvastatin should be used with caution. The initial dose of the drug in such cases should be 5 mg per day. Cautions should be taken with doses above 10 mg / day, and if such doses are deemed necessary, patients should be under close medical supervision.

Patients of advanced age (over 65 years)

There is no need to adjust the dose.

Indications:

Hypercholesterolemia (for patients older than 18 years):

as an addition to the diet, when the application of only diet and other non-drug treatments is not enough for:

decrease in increased concentration of OXC, LDL cholesterol, TG, apolipoprotein B (apo B);
increased HDL cholesterol in patients with primary

hypercholesterolemia, including heterozygous family

hypercholesterolemia (Hyperlipidemia Pa type according to Fredrickson classification) or mixed hypercholesterolemia (hyperlipidemia of Pb type according to Fredrickson classification);

reducing the ratio of LDL / HDL and LDL / LDL cholesterol;

hypertriglyceridemia (type IV hyperlipidemia according to Fredrickson classification);
supplement to the diet and other methods of treatment of patients with homozygous familial hypercholesterolemia to reduce the elevated concentrations of OXC, CHC LHTYP and apo B;
primary dysbetalapoproteinemia (type III hyperlipidemia according to Fredrickson classification).

Patients with ischemic heart disease (CHD) or a high risk of cardiovascular complications (for patients over 18 years of age): in patients with a high risk of cardiovascular complications (in the presence of hyperlipidemia and without it), for example, patients with IHD or a predisposition to IHD, with diabetes mellitus, with stroke or other cerebrovascular diseases in the history, patients with peripheral vascular diseases, the preparation SimvaHEXAL® is shown with the aim of:

reducing the risk of overall mortality by reducing mortality due to coronary artery disease;
reduction of risk of serious vascular and coronary events:

non-fatal myocardial infarction;
coronary death;
stroke;
revascularization procedures.

reduction in the risk of having to conduct

restoration of coronary blood flow;

reduction in the risk of having to conduct

restoration of peripheral blood flow and other types of non-coronary revascularization;

decrease in the risk of hospitalization due to attacks of angina pectoris. Application in children and adolescents 10-17 years with heterozygous familial hypercholesterolemia:

the use of SimvaHEXAL® simultaneously with the diet is shown to reduce the increased concentration of OXC, LDL cholesterol, TG, apo B in young men 10-17 years and girls 10-17 years not less than 1 year after menarche with heterozygous familial hypercholesterolemia.

Contraindications:

hypersensitivity to simvastatin or to other components of the drug, as well as to other drugs of the statin series (inhibitors of HMG-CoA reductase) in the anamnesis;
severe hepatic insufficiency, liver disease in the active stage, persistent increase in the activity of "hepatic" transaminases and plasma of unclear etiology;
simultaneous application with strong inhibitors of isoenzyme CYP3A4 (voriconazole, ketoconazole, itraconazole, posaconazole), HIV protease inhibitors (for example, nelfinavir), boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone;
concomitant treatment with gemfibrozil, cyclosporin or danazol;
rare hereditary forms of intolerance to galactose, deficiency of lactase or impaired absorption of glucose / galactose (because the composition contains lactose);
use in women planning pregnancy and women of reproductive age who do not use reliable methods of contraception;
pregnancy;
the period of breastfeeding;
age up to 18 years (excluding children and adolescents 10-17 years with heterozygous familial hypercholesterolemia).

Carefully:

should be used in patients with severe renal failure (CC less than 30 ml / min); with hereditary muscle diseases; with arterial hypertension; with pronounced metabolic and endocrine disorders (including untreated

hypothyroidism); with a high risk of diabetes; abusing alcohol; elderly patients (over 65 years); with simultaneous application with nicotinic acid in lipid-lowering doses (more than 1 g / day), amiodarone, amlodipine, verapamil, diltiazem, colchicine, fusidic acid, ranolazine, dronedarone (increases the risk of myopathy and rhabdomyolysis), grapefruit juice.

Pregnancy and lactation:

Contraindicated use of the drug SimvaHEXAL® during pregnancy. Due to the fact that inhibitors of HMG-CoA reductase inhibit the synthesis of cholesterol, and cholesterol and other products of its synthesis play an important role in the development of the fetus, including the synthesis of steroids and cell membranes, simvastatin can have an adverse effect on the fetus when used in 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 abolition of lipid-lowering drugs during pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.

There is no data on the allocation of simvastatin in breast milk, so when using the drug in the period of breastfeeding, breastfeeding should be stopped.

Dosing and Administration:

Before starting treatment with SimvaHEXAL®, the patient should be given a standard hypocholesterolemic diet, which must be observed throughout the course of treatment.

SimvaHEXAL® tablets are taken once a day, in the evening, with plenty of water.

Recommended daily doses range from 5 to 80 mg. Dose titration should be performed at intervals of 4 weeks. A dose of 80 mg can be used

Only patients with severe hypercholesterolemia and high cardiovascular risk.

Patients with familial homozygous hypercholesterolemia: the recommended daily dose is 40 mg per day, once in the evening. A dose of 80 mg per day is recommended to be used only if the expected benefit of therapy exceeds the possible risk. In such patients, the preparation SimvaHEXAL® is used in combination with other methods of lipid-lowering treatment (for example, plasmapheresis of LDL) or without such treatment, if it is not available.

Patients with IHD or a high risk of cardiovascular complications The standard initial dose of the drug SimvaHEXAL® for patients at high risk of developing coronary artery disease in combination with or without hyperlipidemia (in the presence of diabetes, a stroke or other cerebrovascular disease in history, peripheral vascular disease), as well as for patients with ischemic heart disease is 40 mg per day .

Patients with hyperlipidemia, not having the above risk factors: the standard starting dose is 20 mg once a day in the evening. In patients with an LDL concentration in the serum that exceeds normal values by 45%, the initial dose may be 40 mg / day. Patients with mild and moderate hypercholesterolemia with SimvaHEXAL can start with an initial dose of 10 mg / day.

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Concomitant therapy: The preparation of SimvaHEXAL can be used both in monotherapy and in combination with bile acid sequestrants.

For patients, simultaneously taking fibrates, apart from

fenofibrate, the maximum daily dose of simvastatin is 10 mg. Concomitant use with gemfibrozilom contraindicated.

Patients, simultaneously accepting verapamil, diltiazem and dronedaron, the maximum daily dose is 10 mg / day.

For patients who simultaneously take amiodarone, amlodipine, ranolazine, the maximum daily dose of simvastatin 20 mg.

Patients with chronic renal insufficiency: in patients with impaired renal function of mild and moderate severity (QC more than 30 ml / min), dose adjustment is not required. In patients with impaired renal function of severe severity (CK less than 30 ml / min) or taking simultaneously fibrates or nicotinic acid (at a dose of more than 1 g / day),the initial dose is 5 mg, and the maximum allowable daily dose is 10 mg.

In elderly patients (over 65 years) correction of the dose is not required. Application in children and adolescents 10-17 years with heterozygous familial hypercholesterolemia: the recommended initial dose is 10 mg per day in the evening. The recommended dosage regimen is 10-40 mg per day, the maximum recommended dose of the drug is 40 mg per day. The choice of doses is carried out individually in accordance with the goals of therapy.

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

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100 to <1/10), infrequently (> 1 / 1,000 to <1/100), rarely (from> 1 / 10,000 to <1 / 1,000), very rarely (<1 / 10,000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

Co hand blood and lymphatic system rarely: anemia (including hemolytic), thrombocytopenia, eosinophilia.

From the nervous system rarely: dizziness, headache, paresthesia, peripheral neuropathy;

rarely: sleep disorders (insomnia, "nightmarish" dreams), depression, loss or loss of memory, blurred vision.

Co hand respiratory systems, organs of the chest and mediastinum

often: infection of the upper respiratory tract;

frequency unknown interstitial lung diseases (especially with prolonged use), bronchitis, sinusitis.

From the heart often: atrial fibrillation.

From the digestive system

often: nausea, gastritis, abdominal pain, constipation;

rarely: vomiting, diarrhea, flatulence, Ankreatitis.

From the side of the liver and bile ducts

rarely: hepatitis, jaundice;

rarely^-. hepatic failure;

frequency is unknown: hepatic insufficiency with lethal

outcome.

From the skin and subcutaneous fabrics

rarely: skin rash, itchy skin integuments, alopecia, photosensitization.

From the musculoskeletal and connective tissue

rarely: myopathy * (including myositis), rhabdomyolysis (with or without

development of acute renal disease insufficiency), myalgia, muscle cramps, polymyositis;

rarely: arthralgia, arthritis;

frequency is unknown: tendinopathy, possibly with rupture of the tendon.

*at clinical studies of myopathy was observed more often in patients,

applying simvastatin in a dose of 80 mg / day in comparison with patients, using a dose of 20 mg / day (1.0 / o versus 0.02%, respectively).

FROMabout hand kidneys and urinary tract

frequency is unknown: acute renal insufficiency (due to rhabdomyolysis), urinary tract infections.

From the genitals and breast

frequency is unknown: erectile dysfunction, gynecomastia.

General disorders and disorders at the site of administration

rarely: general weakness.

Allergic reactions

rarely: angioedema, rheumatic polymyalgia,

vasculitis, increased erythrocyte sedimentation rate (ESR), positive titers antinuclear antibodies, hyperemia of the skin of the face, lupus syndrome, dyspnea, general malaise; frequency is unknown: immuno-mediated necrotizing myopathy, toxic epidermal necrolysis (Lyell's syndrome), polymorphic erythema, including Steven-Johnson syndrome.

Laboratory indicators:

rarely: increased activity of "hepatic" transaminases, CK and alkaline phosphatase in blood plasma;

frequency is unknown: increase in the concentration of glycosylated hemoglobin, hyperglycemia.

When other statins were used, the following additional undesirable effects were recorded:

memory loss
cognitive impairment
diabetes. The frequency of diabetes depends on the presence of risk factors (fasting blood glucose more than 5.6 mmol / L, body mass index more than 30 kg / m, increased thyroglobulin (TG) in blood plasma, history of hypertension).

Children and adolescents (10-17 years) According to a study of 1 year duration in children and adolescents (boys in the Tanner stage II and above, and girls, at least one year after the first menstruation) at the age of 10-17 years with heterozygous familial hypercholesterolemia (n = 175), the safety and tolerability profile in the group using simvastatin, was similar to the profile of the placebo group. The most common adverse events were upper respiratory tract infections, headache, abdominal pain, nausea. Long-term the impact on physical, intellectual and sexual development is not known. At the moment (after a year after treatment), there is insufficient safety data.

Overdose:

To date, no specific symptoms of drug overdose (maximum accepted dose of 3.6 g) have been identified.

Treatment: symptomatic therapy. The specific antidote is not known.

Interaction:

The study of interaction with other drugs was carried out only in adults. Pharmacodynamic interactions

Interactions with other lipid-lowering drugs that can lead to increase the risk of development

myopathy / rhabdomyolysis

Fibrates

The risk of myopathy, including rhabdomyolysis, increases during simultaneous use of simvastatin with fibrates. Joint application with gemfibrozil leads to increased plasma the concentration of simvastatin, therefore their joint the use is contraindicated.

There is no evidence of an increased risk of myopathy simultaneous application simvastatin and fenofibrate. Controlled studies on the interaction with other fibrates not carried out.

A nicotinic acid There are isolated reports of the development of myopathy / rhabdomyolysis with the simultaneous use of simvastatin and nicotinic acid in the lipid-lowering dose (more than 1 g / day).

Fusidic acid

The risk of developing myopathy increases with simultaneous application fusidic acid with statins, including simvastatin. If it is impossible for some reason to avoid simultaneous application of simvastatin with fusidic acid, it is recommended that possibility to postpone treatment with simvastatin. When the need for their simultaneous use, patients should be carefully monitored.

Pharmacokinetic interactions Recommendations for the use of interacting drugs are given in the table.

Drug interactions
funds associated with
increased risk of development
myopathy / rhabdomyolysis

Interacting	Recommendations
other drugs	on application
Strong	Contraindications
inhibitors	but
isoenzyme	simultaneous
CYP3A4:	application from

Itraconazole	simvastatin
Ketoconazole
Posaconazole
Voriconazole
Erythromycin
Clarithromycin
Telithromycin
Inhibitors
HIV proteases
(eg,
nelfinavir)
Nefazodone
Cyclosporin
Gemfibrozil
Danazol
Preparations,
containing
cobicystate
Other fibrates	Do not exceed
(Besides	a dose of 10 mg
fenofibrate)	simvastatin
Verapamil	daily
Diltiazem
Dronedaron
	Do not exceed
Amiodarone	a dose of 20 mg
Amlodipine	simvastatin
Ranolazine	daily
	Required
	attentively
	watch for
	patients.
	Possible
Fusidic acid	temporary

	annulment
	simvastatin.
	Do not consume grapefruit juice in large quantities (more than 1 liter per day) during
G raipfruit	applications
juice	simvastatin

ATThe loss of other drugs on the pharmacokinetics of simvastatin

Strong inhibitors isoenzyme CYP3A4

Simvastatin is a substrate of isoenzyme CYP3A4. Powerful inhibitors of isoenzyme CYP3A4 increase the risk of myopathy and rhabdomyolysis by increasing the inhibitory activity of HMG-CoA reductase in blood plasma during treatment with simvastatin. Such inhibitors include itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors (eg, nelfinavir), as well as nefazodone.

Simultaneous application simvastatin with itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, an HIV protease inhibitor (eg, nelfinavir), and nefazonone is contraindicated. If it is impossible for some reason to avoid combined use of simvastatin with the above drugs, it should be postponed treatment with simvastatin before end of the course of treatment with these drugs.

Caution should be exercised use simvastatin with some less potent inhibitors CYP3A4: fluconazole, verapamil or diltiazem.

Fluconazole

Rare cases of rhabdomyolysis, associated with simultaneous using simvastatin and fluconazole.

Cyclosporin

Contraindicated simultaneous use of cyclosporine and

simvastatin.

Danazol

Risk of development myopathy / rhabdomyolysis increases with simultaneous danazol, especially high doses of simvastatin.

Amiodarone

The risk of developing myopathy and rhabdomyolysis increases with simultaneous application amiodarone with high doses simvastatin. In clinical research on the development of myopathy was found in 6% of patients who used simvastatin in a dose of 80 mg together with amiodarone. Therefore, the dose of simvastatin should not exceed 20 mg per day in patients who simultaneously use the drug with amiodarone, if the clinical benefit exceeds the risk of developing myopathy and rhabdomyolysis.

Blockers "slow" calcium channels

Verapamil

The risk of developing myopathy and rhabdomyolysis increases with simultaneous application verapamil with simvastatin in doses greater than 40 mg. Dose simvastatin should not exceed 10 mg per day for patients using the drug simultaneously with verapamil, if clinical benefit exceeds risk of myopathy and rhabdomyolysis.

Diltiazem

The risk of developing myopathy and rhabdomyolysis increases with simultaneous application diltiazem and simvastatin in a dose 80 mg. At simultaneous the use of simvastatin in a dose 40 mg with diltiazem risk of developing Myopathy did not increase. Dose simvastatin should not exceed 10 mg per day for patients using concomitantly with diltiazem, if the clinical benefit exceeds risk of development myopathy / rhabdomyolysis.

Amlodipine

Patients using Amlodipine concurrently with simvastatin at a dose of 80 mg, fall into the group at increased risk of myopathy. With simultaneous application simvastatin in a dose of 40 mg with amlodipine, the risk of myopathy did not increase. With simultaneous application simvastatin with amlodipine, the dose of simvastatin should not exceed 20 mg per day if the clinical benefit exceeds the risk of developing myopathy / rhabdomyolysis.

Other interactions Grapefruit juice Grapefruit juice contains one or more components that inhibit the isoenzyme CYP3A4 and can increase the concentration in the blood plasma of drugs metabolized by the isoenzyme CYP3A4. When you drink juice in the usual amount (one glass of 250 ml in day), this effect is minimal (an increase of 13% in the activity of HMG-CoA reductase inhibitors by estimating the area under the concentration-time curve) and has no clinical significance. However, the consumption of grapefruit juice in very large volumes (more than 1 liter per day) significantly increases the plasma level of the activity of HMG-CoA reductase inhibitors during simvastatin therapy. In this regard, you must avoid the consumption of grapefruit juice in large quantities.

Colchicine

There are reports of myopathy / rhabdomyolysis in simultaneous application Colchicine and simvastatin in patients with renal disease insufficiency. Patients using concomitantly these drugs should be under the supervision of a doctor.

Rifampicin

As rifampicin is a strong inducer of isoenzyme CYP3A4, in patients, long-term host this preparation (for example, treatment of tuberculosis), possibly lack of effectiveness application of simvastatin (lack of achievement of target cholesterol concentration in blood plasma).

The effect of simvastatin on pharmacokinetics of other medications

Simvastatin does not render inhibitory effect on isoenzyme CYP3A4. Therefore, what simvastatin does not affect plasma concentration substances metabolized by isoenzyme CYP3A4.

Digoxin

There is a message that when simultaneous application digoxin and simvastatin slightly increases plasma concentration of the first, so you should carefully monitor patients, host digoxin, especially at the beginning of therapy withimvastatin.

Indirect anticoagulants In two clinical one of which was conducted on healthy volunteers, and the other on patients with hypercholesterolemia, simvastatin in a dose of 20-40 mg / day moderately enhanced the action of coumarin anticoagulants. The international normalized ratio (INR) increased from 1.7-1.8 to 2.6-3.4 in healthy volunteers and patients, respectively. In patients using coumarin anticoagulants, prothrombin time (PI) or INR should be determined before treatment and, in the future, often determined at the initial stage of treatment with simvastatin to ensure no significant changes in MI / INR. After establishing a stable PV / INR value, it can be monitored at time intervals, recommended for patients taking coumarin aanticoagulants. When changing the dose of simvastatin, or interrupting treatment, the frequency of control of MI / INR should be increased. Occurrence bleeding or changes in MI / INR in patients not using anticoagulants is not associated with the use of

simvastatin.

Special instructions:

In the period of treatment with the drug SimvaHEXAL ® in rare cases, dizziness, drowsiness, headache,therefore, care should be taken when driving vehicles and performing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

CK activity

If a patient has increased the activity of CKK with the SymwaHEXAL® drug and muscle symptoms have appeared, other causes of increased enzyme activity should be excluded: intense physical activity, trauma, bruises, fever, hypothyroidism, infections, carbon dioxide poisoning, polymyositis, dermatomyositis, alcohol abuse, narcotic means.

Before using the drug SimvaHEXAL® it is necessary to perform a blood test for the activity of CKK. In elderly patients (over 65 years of age), with hypothyroidism, type 2 diabetes (insulin-independent diabetes), asthenic constitution, impaired renal function receiving combined therapy of statins with fibrates, it is recommended to repeat the activity of CKK every 3 months during the first year of therapy . Control of the activity of CK in patients without symptoms of myopathy receiving therapy with the drug SimvaHEXAL® is not required.

If the patient develops symptoms of myopathy and excludes secondary causes of it, regardless of the activity of CKK, the preparation of SimvaHEXAL should be discontinued.

If the patient exhibits an asymptomatic increase in CKK activity by more than 5 times compared with the upper limit of the norm, therapy with SimvaHEXAL® can be continued with subsequent monitoring of the activity of CKM monthly until it normalizes.

Before treatment begins

All patients before the start of treatment with the drug SimvaHEXAL® or patients in whom the dose of the drug was increased, it is necessary to warn about the risk of myopathy, and patients are asked to immediately report any unexplained muscle pain, sensation of pain or weakness.

Care should also be taken in patients with a predisposition to rhabdomyolysis. It is necessary to determine the activity of CKK before treatment in the following situations:

Elderly patients (age over 65)
Women
Impaired renal function
Untreated hypothyroidism
Personal or family anamnesis of hereditary muscle disorders
Reactions of muscle toxicity in taking a statin or fibrate in an anamnesis
Excessive consumption of alcohol (ethanol)

In these situations, it is necessary to assess the relationship between the risk of treatment and the possible benefits, and careful monitoring of the patient is also recommended. If the patient has previously had an anomalous myopathy associated with taking a fibrate or a statin, caution should be taken with a drug from the same group. If the activity of CK exceeds the value of the upper limit of the norm more than 5 times, then treatment should not begin.

During the treatment period

If during the treatment with the drug SimvaHEXAL® the patient has muscle pain, weakness, spasms, it is necessary to evaluate the activity of CKK. If the activity of CK exceeds the value of the upper limit of the norm by more than 5 times, then the treatment should be stopped. If the muscle symptoms are severe and cause daily discomfort, even with the activity of CK, which does not exceed 5 times the upper limit of the norm, consideration should be given to the possibility of discontinuing drug treatment. If there is a suspicion of myopathy for any other reason, treatment with SimvaHEXAL® should be discontinued.

After the disappearance of symptoms and the restoration of normal activity of CK, it is permissible to consider the possibility of resuming treatment with the drug SimvaHEXAL®, or the use of an alternative statin in the lowest possible dose and with the careful supervision of a physician.

Characteristics of the use of the drug SimvaHEXAL® with other medicinal products, see the section "Interaction".

Diabetes

The drug SimvaGEKSAL® increases in plasma glucose concentration, so some patients from the risk group of diabetes may experience hyperglycemia requiring medical correction. However, reducing the risk of complications from the blood vessels in the application of statins exceed the risk of hyperglycemia, so when the concentration of glucose in the blood should not interrupt treatment with SimvaGEKSAL®. Use of the drug in patients at risk (glucose concentration in fasting 5.6 - 6.9 mmol / l; body mass index greater than 30 kg / m, increased plasma levels of TG, hypertension) probably by careful observation of their physician.

Effects on the liver

At the beginning of therapy with the preparation of SimvaHEXAL®, there may be a transient increase in the activity of "liver" transaminases in the blood serum.

Before starting treatment, and then according to clinical indications, all patients are recommended to perform liver function tests (to monitor the activity of "liver" transaminases before increasing the dose of the drug SimvaHEXAL®, then 3 months after the beginning of its use and then 1 time in six months during the first year of treatment). Particular attention should be given to patients with increased activity of "liver" transaminases. When persistently increasing the activity of "liver" transaminases (3 or more times higher than the upper limit of the norm), the use of the preparation of SimvaHEXAL® should be discontinued.

In patients with reduced thyroid function (hypothyroidism) or in the presence of certain kidney diseases (nephrotic syndrome) with nAn increase in the concentration of cholesterol should be followed first with treatment of the underlying disease.

Interstitial lung disease

With prolonged use of statins, it is possible in rare cases to develop interstitial lung disease (dyspnea, dry cough, worsening general health - increased fatigue, weight loss, chills). With the development of these symptoms, the use of the SimvaHEXAL® drug should be stopped immediately.

Application in children and adolescents (10-17 years)

Safety and efficacy of the drug in children and adolescents aged 10-17 years with heterozygous familial hypercholesterolemia were evaluated in controlled clinical trials involving 10-17 year olds and 10-17 year olds not less than 1 year after menarche. In patients of child age, who used simvastatin, the side effect profile was similar to that of patients taking placebo. The use of the drug SimvaHEXAL® in a dose of more than 40 mg in children of childhood was not studied. In this study, there was no effect of the drug on the growth and puberty of young men and girls or any effect on the length of the menstrual cycle in girls.

Girls should be informed of appropriate contraceptive measures during drug treatment. The use of simvastatin has not been studied in children under 10 years of age or in girls 10-17 years before the menarche. Simultaneous use of a large amount (more than 1 liter per day) grapefruit juice may increase the severity of side effects associated with the use of the drug SimvaHEXAL, therefore, their joint administration should be avoided.

The drug SimvaHEXAL® is not indicated in cases where there is hypertriglyceridemia of types I and V.

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

The data of modern long-term clinical studies do not contain information on the adverse effects of simvastatin on the lens of the human eye.

Peculiarities of pharmacokinetics in various races

In patients of Chinese nationality who apply together simvastatin in a dose of 40 mg per day and nicotinic acid in lipid-lowering doses (more than 1 g per day) increased the risk of myopathy. It should be used with caution simvastatin in a dose of more than 20 mg per day in conjunction with lipid-lowering doses of nicotinic acid in patients of Chinese nationality. The cause of increased risk of myopathy in this case is unknown. It is also unknown whether patients from other Asian countries have an increased risk of developing myopathy due to the joint use of simvastatin with nicotinic acid in lipid-lowering doses found in Chinese patients.

Treatment with the drug SimvaHEXAL® is recommended to be temporarily stopped a few days before the planned surgicalinterference.

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

In the period of treatment with the drug SimvaHEXAL®, dizziness, drowsiness and headache may occur rarely, therefore, care should be taken when driving vehicles and performing other potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets coated with 5 mg, 10 mg, 20 mg, 30 mg, 40 mg.

For 10 tablets in a blister made of polyvinylchloride and aluminum foil.

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

Packaging:

For 10 tablets in a blister made of polyvinylchloride and aluminum foil.

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

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the medicinal product after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015775 / 01

Date of registration:15.05.2009

The owner of the registration certificate:HEXAL AG HEXAL AG Germany

Manufacturer: & nbsp

HEXAL AG Germany

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp31.07.2015

Illustrated instructions

Instructions

SimvaHEXAL® (SimvaHEXAL ®)