Torvakard

General characteristics. Structure:

Each tablet, film coated, contains:
active agent:
аторвастатин 10 mg (in the form of an atorvastatin of calcium of 10,34 mg),
аторвастатин 20 mg (in the form of an atorvastatin of calcium of 20,68 mg),
аторвастатин 40 mg (in the form of an atorvastatin of calcium of 41,36 mg);
excipients:
kernel: magnesium oxide, cellulose microcrystallic, lactoses monohydrate,  the croscarmellose sodium, a hypro rod low-replaced silicon dioxide colloid, magnesium stearate;
film cover: gipromelloza 2910/5, macrogoal 6 000, titanium dioxide, talc.

DESCRIPTION
 From white till almost white color oval biconvex tablets, film coated.

Pharmacological properties:

Pharmacodynamics. Hypolipidemic means from group of statines. The selection competitive inhibitor of GMG-KOA-reduktazy - the enzyme turning 3-hydroxy-3-methylglutaryl coenzyme A into mevalonovy acid, being the predecessor of sterol including cholesterol. Triglycerides (TG) and cholesterol in a liver are included lipoproteins of very low density (LPONP), come to a blood plasma and are transported in peripheral fabrics. Lipoproteins of the low density (LPNP) are formed of LPONP during interaction with LPNP receptors. Atorvastatin reduces concentration of cholesterol and lipoproteins in a blood plasma at the expense of inhibition of GMG-KOA-reduktazy, synthesis of cholesterol in a liver and increases in number of "hepatic" receptors of LPNP at surfaces of cells that leads to strengthening of capture and a catabolism of LPNP. Reduces formation of LPNP, causes the expressed and permanent increase in activity of LPNP-receptors. Reduces concentration of LPNP at patients with a homozygous semeyyony hypercholesterolemia which usually does not give in to therapy by hypolipidemic means. Reduces concentration of the general cholesterol by 30-46%, LPNP - for 41-61%, apolipoprotein B - for 34-50% and TG - for 14-33%; causes increase in concentration holesterina-LPVP (lipoproteins of high density) and A. Dozozavisimo's apolipoprotein reduces concentration of LPNP at patients with a homozygous hereditary hypercholesterolemia, resistant to therapy by other hypolipidemic means.

Pharmacokinetics. Absorption - high. The maximum concentration (Cmax) in a blood plasma is reached in 1-2 h, Cmax at women is 20% higher, the area under a curve "concentration - time" (AUC) - is 10% lower; Cmax at patients with alcoholic cirrhosis by 16 times, AUC - is 11 times higher than norm. Food reduces the speed and duration of absorption of drug a little (by 25% and 9% sootvetyostvenno), however decrease in LPNP cholesterol is similar to that at use of an atorvastatin without food. Concentration of an atorvastatin at use is lower in the evening, than in morning (approximately for 30%). Linear dependence between extent of absorption and a dose of drug is revealed.
Bioavailability - 12%, system bioavailability of the inhibiting activity concerning GMG-KOA-reduktazy - 30%. Low system bioavailability is caused by a presistemny metabolizyom in a mucous membrane of digestive tract and at "the first passing" through a liver.
The average volume of distribution - 381 l, communication with proteins of a blood plasma - 98%. It is metabolized preferential in a liver under the influence of isoenzymes of CYP3A4, CYP3A5 and CYP3A7 with an obrazoyovaniye pharmacological of active metabolites (orto-and parahydroxylated derivatives, beta oxidation products). In vitro orto-and paragidroksilirovainy metabolites have an inhibiting effect on GMG-KOA-reduktazu, comparable  to that of an atorvastatin.
The inhibiting effect of drug concerning GMG-KOA-reduktazy approximately for 70% opredelyayotsya by activity of the circulating metabolites.
It is removed through intestines with bile after hepatic and/or extrahepatic metabolism (is not exposed to the expressed enterohepatic recirculation).
Elimination half-life - 14 h. The inhibiting activity concerning GMG-KOA-reduktazy remains about 20-30 h thanks to existence of active metabolites. Less than 2% of the dose of drug accepted inside are defined in urine. It is not removed during a hemodialysis.

Indications to use:

• In combination with a diet for decrease in the increased concentration of the general cholesterol, cholesterol/LPNP, apolipoprotein B and triglycerides and increase in concentration of LPVP cholesterol at patients with primary hypercholesterolemia, a heterozygous family and single hypercholesterolemia and the combined (mixed) lipidemia (the IIA and IIb types across Frederikson);
• In combination with a diet for treatment of patients with the increased serumal concentration of triglycerides (a family endogenous gipertriglitseridemiya of the IV type across Frederikson) and patients with a disbetalipoproteinemiya (type III across Frederikson) at whom the dietotherapy does not give adequate effect;
• For decrease in concentration of the general cholesterol and cholesterol/LPNP at patients with a homozygous family hypercholesterolemia when the dietotherapy and other not pharmacological methods of treatment are insufficiently effective (as addition to hypolipidemic therapy, including autohemotrasfusion of the blood purified of LPNP)
• Diseases of cardiovascular system (at the patients having the increased risk factors of emergence of an ischemic heart disease - advanced age is more senior than 55 years, smoking, arterial hypertension, a diabetes mellitus, diseases of peripheral vessels, the had stroke, a hypertrophy of a left ventricle, протеин-/an albuminuria, an ischemic heart disease at the immediate family), including against the background of a dislipidemiya - secondary prevention for the purpose of decrease in total risk of death, a myocardial infarction, a stroke, repeated hospitalization concerning stenocardia and need for the procedure of revascularization.

Route of administration and doses:

Before purpose of the drug TORVAKARD® the patient needs to recommend a standard gipokholesterinemichesky diet which he has to continue to observe during the entire period of therapy.
To accept drug inside at any time, irrespective of meal time. Learn on this website as it is long possible to accept Torvakard whether we will combine this drug with alcohol.
The initial dose averages 10 mg of 1 times/days. The dose varies from 10 to 80 mg of 1 times/days. The dose is selected taking into account initial concentration of cholesterol/LPNP, purpose of therapy and individual effect. In an initiation of treatment and/or during increase in a dose of the drug TORVAKARD® it is necessary to control each 2-4 weeks concentration of lipids in a blood plasma and as appropriate to adjust a dose. The maximum daily dose - 80 mg in 1 reception.
Primary hypercholesterolemia and the mixed lipidemia
 In the majority cases there is enough purpose of a dose of 10 mg of the drug ТОРВАКАРД® 1 of times in days. The essential therapeutic effect is observed  in 2 weeks , as a rule, and the maximum therapeutic effect is usually observed in 4 weeks. At prolonged treatment this effect remains.
When determining the purpose of treatment it is possible to use the following recommendations.
A. Recommendations of the National educational program for cholesterol (USA)

Diagnosed      Existence 2 more or                    Cholesterol/LPNP, 
atherosclerosis of vessels *  more risk factors **              mg/dl (mmol/l)
                                                                            Initial           Minimum purpose
                                                                            concentration

                                Is not present                                > 190 (> 4,9)        <160 (<4,1)
Is not present                                Yes                                  > 1b0 (> 4,1)        <130(<3,4)
                                 Yes or not                      > 130 ***            <100 (<2,6)
                                                                              (> 3,4)

* An ischemic heart disease  or  atherosclerosis  of peripheral  vessels  (including  the defeat of carotid arteries which is followed by clinical symptoms).
 ** Include the following: age (the man> of 45 years, women> 55 years or an early menopause at which replacement therapy is not carried out by estrogen), ischemic heart disease prematurity cases at relatives, smoking, arterial hypertension, the confirmed cholesterol/LPVP value <35 mg/dl <0,91 mmol/l) and a diabetes mellitus. It is necessary to subtract one risk factor if cholesterol/LPVP value makes> 60 mg/dl (> 1.6 mmol/l),
 *** At patients with an ischemic heart disease with value of cholesterol / LPNP from 100 to 129 mg/dl the issue of purpose of medicinal therapy is resolved by the doctor taking into account clinical experience.

B. Recommendations of the European society of atherosclerosis (EAS) concerning diagnosis and treatment of disturbances of metabolism
- purposes of hypolipidemic therapy of the European society of atherosclerosis
 At patients with the confirmed diagnosis of an ischemic heart disease and other patients with high risk of ischemic complications the purpose of treatment is decrease in cholesterol/LPNP value <3 mmol/l (or <115 mg/dl) and the general cholesterol <5 mmol/l (or <190 mg/dl).

B. National recommendations about treatment
Homozygous family hypercholesterolemia.
In a research at adult patients with a homozygous family hypercholesterolemia therapy atorvastatiny in a dose of 80 mg a day in most cases led to decrease in cholesterol/LPNP value more than for 15% (18-45%).
Use of drug for patients with a renal failure and diseases of kidneys does not exert impact on concentration of an atorvastatin in a blood plasma or extent of decrease in cholesterol/LPNP value at its use therefore change of a dose of drug is not required.
At use of drug for elderly patients of distinctions in safety, efficiency or achievement of goals of hypolipidemic therapy in comparison with the general population it was not noted.

Features of use:

Before therapy by the drug TORVAKARD® it is necessary to try to achieve control of a hypercholesterolemia by an adequate dietotherapy, increase in physical activity, decrease in body weight from patients with obesity and treatments of other states. Use of inhibitors of GMG-KOA-reduktazy for decrease in level of lipids in blood can lead to change of biochemical indicators of function of a liver which should be controlled before therapy, in 6 and 12 weeks after the beginning of administration of drug ТОРВАКАРД® and after each increase in a dose, and also periodically, for example, each 6 months. Increase in activity of "hepatic" transaminases in blood serum can be observed during therapy by the drug TORVAKARD® (usually in the first three months). Patients at whom increase in level of activity of "hepatic" transaminases is noted have to be under control before return of level of enzymes to norm. If ACT or ALT values are more than 3 times higher than norm, it is recommended to lower a dose of drug TORVAKARD or to stop treatment.
Treatment by the drug TORVAKARD® can cause a myopathy (pains and weakness in muscles in combination with increase in activity of KFK more than by 10 times in comparison with the upper bound of norm). ТОРВАКАРД® can cause increase in indicators of serumal KFK that it is necessary to take into account at differential diagnosis of retrosternal pains. Patients need to be warned that they should see immediately a doctor at emergence of inexplicable pains or weakness in muscles, especially, if they are followed by an indisposition or fever. Therapy by the drug TORVAKARD® should be stopped temporarily or to cancel completely at emergence of signs of a possible myopathy or existence of risk factor of development of a renal failure against the background of a rabdomioliz (for example, a heavy acute infection, arterial hypotension, serious surgical intervention, an injury, heavy exchange, endocrine and electrolytic disturbances and uncontrollable spasms).

Influence on ability to manage vehicles and occupation other types of activity demanding concentration of attention and speed of psychomotor reactions
 Film coated on ability to manage vehicles and and occupation was not reported by other types of activity demanding concentration of attention and speed of psychomotor reactions about adverse influence of the drug TORVAKARD®, a tablet.

Side effects:

Frequency of the side reactions given below was defined according to the following (classification of World Health Organization):
very often - more than 1/10,
often - from more than 1/100 to less than 1/10,
infrequently - from more than 1/1000 to less than 1/100,
seldom - from more than 1/10000 to less than 1/1000,
very seldom - from less than 1/10000, including separate messages.
From the central nervous system:
often - a headache, an adynamy, sleeplessness;
infrequently - dizziness, drowsiness, dreadful dreams, amnesia, a depression, peripheral neuropathy, an ataxy, hypesthesias, paresthesias.
From the alimentary system:
often - nausea, vomiting, a lock or diarrhea, a meteorism, a gastralgia, an abdominal pain;
infrequently - anorexia or increase in appetite, hepatitis, pancreatitis, cholestatic jaundice.
 From a musculoskeletal system: 
very often - a mialgiya; arthralgia; 
infrequently - a myopathy;
seldom - a miositis, рабдомиолиз, a dorsodynia, spasms of gastrocnemius muscles of legs.
Allergic reactions:  
often - a skin itch,  rash;  
infrequently - a small tortoiseshell;  
 very seldom - a Quincke's   disease, an acute   anaphylaxis,   violent   rashes,   a poliformny exudative erythema, including Stephens-Johnson's syndrome, a toxic epidermal necrolysis (Lyell's disease).
Laboratory indicators:
infrequently - a hyperglycemia, a hypoglycemia, increase in activity of a serumal kreatinfosfokinaza (KFK), increase in activity of aspartate aminotransferase (ACT) and alaninaminotranspherase (ALT).
Others:
often - a stethalgia, peripheral hypostases;
infrequently - impotence, an alopecia, a sonitus, increase in body weight, an indisposition, weakness, thrombocytopenia, a secondary renal nedostayotochnost.

Interaction with other medicines:

During treatment by drugs of a class of hypolipidemic means and the simultaneous use of cyclosporine, fibrat, erythromycin, a klaritromitsin, immunodepressive and protivoyogribkovy drugs (relating to azoles), niacin and niacinamide, drugs inhibiting metabolism mediated by R450ZA4 cytochrome isoenzymes, and/or транс­порт medicines, concentration of an atorvastatin in a blood plasma (and risk of emergence of a myopathy) raises. Appointing these drugs it is necessary to weigh carefully expected advantage and risk of treatment, to regularly observe patients for the purpose of detection of pains or weakness in muscles, especially within the first months of treatment and during increase in a dose of any drug, to periodically carry out definition of activity of KFK though such control does not allow to prevent development of a heavy myopathy. Therapy by the drug TORVAKARD® should be stopped in case of the expressed increase in activity of KFK or in the presence of the confirmed or estimated myopathy.
Atorvastatin did not exert clinically significant impact on concentration of a terfenadin in a blood plasma which is metabolized, mainly, by R45oza4 cytochrome isoenzymes; in this regard it is represented  a little probable that аторвастатин it is capable to influence pharmacokinetic parameters of other substrates of isoenzymes of P^5oza4 cytochrome significantly. At simultaneous use of an atorvastatin (on 10 mg of 1 times a day) and azithromycin (on 500 mg of 1 times a day) concentration of an atovastatin in a blood plasma does not change.
At a concomitant use in an atorvastatin and drugs, the containing magnesium and Aluminium hydroxydatum, concentration of an atorvastatin in a blood plasma decreased approximately by 35%, however extent of reduction of the cholesterol/LPNP level at the same time did not change.
At simultaneous use of a kolestipol concentration of an atorvastatin in  a blood plasma decreased approximately by 25%. However the hypolipidemic effect of a combination of an atorvastatin and kolestipol surpassed that of each drug separately.
At simultaneous use аторвастатин does not influence phenazone pharmacokinetics therefore interaction with other drugs, the metabolized same isoenzymes of R450ZA4 cytochrome is not expected.
When studying interaction of an atorvastatin with warfarin, Cimetidinum, phenazone of signs of clinically significant interaction it is not revealed.
Simultaneous use with the drugs reducing concentration of endogenous steroid hormones (including Cimetidinum, ketokonazoly, Spironolactonum), increases risk of decrease in endogenous steroid hormones (it is necessary to be careful).
Clinically significant undesirable interaction of an atorvastatin   and antihypertensives, and also with estrogen is noted.
At simultaneous use of an atorvastatin in a dose of 80 mg/days and oral contraceptives containing norethindrone and ethinylestradiol     substantial increase of concentration of norethindrone and ethinylestradiol approximately for 30% and 20% respectively was observed. This effect should be considered at the choice of an oral contraceptive for the women receiving ТОРВАКАРД®.
At simultaneous use of an atorvastatin of 80 mg and an amlodipina of 10 mg the pharmacokinetics of an atorvastatin in an equilibrium state did not change.
At repeated reception of digoxin and an atorvastatin in a dose of 10 mg equilibrium concentration of digoxin in a blood plasma did not change. However at use of digoxin in a combination with atorvastatiny in a dose of 80 mg/days concentration of digoxin increased approximately by 20%.
The patients receiving digoxin in combination with atorvastatiny should be observed.
Interaction researches with other drugs were not conducted.

Contraindications:

• Hypersensitivity to drug components;
• Active  diseases of a liver or increase in serumal activity of "hepatic" transaminases (more than by 3 times in comparison with the upper bound of norm) not clear genesis, a liver failure (severity And yes In on a scale of Chayld-Pyyu);
• Hereditary diseases, such as a lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption (in connection with existence in composition of lactose);
• Pregnancy, lactation period;
• The women of reproductive age who are not using adequate methods of contraception;
• Age up to 18 years (efficiency and safety are not established).

With care:
alcohol abuse, liver diseases in the anamnesis, the expressed disturbances of water and electrolytic balance, endocrine and metabolic disturbances, arterial hypotension, heavy acute infections (sepsis), uncontrollable epilepsy, extensive surgical interventions, injuries, diseases of skeletal muscles.

Use at pregnancy and in the period of a lactation
 Use for women of reproductive age is possible only in case of use of reliable methods of contraception and the patient is informed on possible risk of treatment for a fruit.
As the cholesterol and substances synthesized from cholesterol are important for fetation, the potential risk of inhibition of HMG-CoA reductase exceeds advantage of use of drug  during pregnancy. At use by mothers in the I trimester of pregnancy of a lovastatin (GMG-KOA-reduktazy inhibitor) with dekstroamfetaminy cases of the birth of children with deformation of bones, tracheooesophageal  fistula,  an anus atresia are known. In case of diagnosing of pregnancy in the course of therapy by the drug TORVAKARD®, administration of drug has to be immediately stopped, and patients are warned about potential risk for a fruit.
In need of use of drug in the period of a lactation, considering a possibility of the undesirable phenomena at  babies, it is necessary to resolve an issue of the breastfeeding termination.

Overdose:

Treatment: there is no specific antidote, symptomatic therapy is carried out. The hemodialysis is inefficient.

Storage conditions:

Does not demand special storage conditions. To store in the place, unavailable to children! Period of validity 2 years. Drug cannot be used after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 10 mg, 20 mg and 40 mg.
On 10 tablets in the blister from A1/A1. On 3 or 9 blisters are placed in a cardboard pack together with the application instruction.