medicalmeds.eu Medicines Hypolipidemic means - KOA-reductase GMG inhibitor. Аторис®

Аторис®

Producer: Krka Russia

Code of automatic telephone exchange: C10AA05

Release form: Firm dosage forms. Tablets.

Indications to use: Diabetes mellitus. Arterial hypertension. Nicotine addiction. Homozygous family hypercholesterolemia. Family endogenous gipertriglitseridemiya. Disbetalipoproteinemiya. Lipidemia. Primary hypercholesterolemia. Stenocardia. Stroke. Acute myocardial infarction. Dislipidemiya.

General characteristics. Structure:

Tablets, film coated 1 table.
active agent:
аторвастатин calcium of 10,36 mg
20,72 mg
(10 or 20 mg of an atorvastatin respectively are equivalent)
excipients: povidone; sodium lauryl sulfate; calcium carbonate; MKTs; lactoses monohydrate; sodium of a kroskarmelloz; magnesium stearate
the cover is film: Opadry II HP 85F28751 white (polyvinyl alcohol, titanium dioxide (E171), macrogoal 3000, talc)

Tablets, film coated 1 table.
active agent:
аторвастатин calcium of 31,08 mg
(30 mg of an atorvastatin are equivalent)
61,16 mg
(60 mg of an atorvastatin are equivalent)
82,88 mg
(80 mg of an atorvastatin are equivalent)
excipients: lactoses monohydrate; MKTs; hypro rod; croscarmellose sodium; кросповидон, type A; polysorbate 80; sodium hydroxide; magnesium stearate
the cover is film: Opadry II HP 85F28751 white (polyvinyl alcohol, titanium dioxide (E171), macrogoal 3000, talc)

Tablets, film coated 1 table.
active agent:
аторвастатин calcium of 41,44 mg
(40 mg of an atorvastatin are equivalent)
excipients: povidone; sodium lauryl sulfate; calcium carbonate; MKTs; lactoses monohydrate; sodium of a kroskarmelloz; кросповидон; magnesium stearate
cover: Opadry White Y-1-7000 (gipromelloza, titanium dioxide (E171), macrogoal 400)

Description of a dosage form

Tablets on 10 or 20 mg: round, slightly biconvex, film coated white color. A look on a break: white weight with a rough surface.

Tablets on 30 mg: round, slightly biconvex, film coated white or almost white color, with a facet.

Tablets on 40 mg: round, slightly biconvex, film coated white or almost white color.

Pharmacological properties:

Pharmacodynamics. Atorvastatin — hypolipidemic means from group of statines. The main mechanism of action of an atorvastatin is the activity inhibition 3-hydroxy-3-methylglutaryl-coenzyme A - (ГМГ-КоА-) reductases — the enzyme catalyzing transformation GMG-KOA into mevalonovy acid. This transformation is one of early stages in a chain of synthesis of cholesterol in an organism. Suppression atorvastatiny synthesis of cholesterol leads to increase in reactivity of receptors of LPNP in a liver, and also in extrahepatic fabrics. These receptors connect particles of LPNP and delete them from a blood plasma that leads to decrease in level of LPNP cholesterol in blood.

The anti-atherosclerotic effect of an atorvastatin is a consequence of impact of drug on walls of vessels and components of blood. Drug suppresses synthesis of the isoprenoids which are growth factors of cells of an internal cover of vessels. Under the influence of an atorvastatin endoteliyzavisimy expansion of blood vessels improves. Atorvastatin reduces the content of cholesterol, LPNP, apolipoprotein B, triglycerides. Causes increase in content of LPVP cholesterol and apolipoprotein A. Atorvastatin increases the serumal Hs-LPVN levels and reduces values of ratios Hs-LPNP/Hs-LPVP and the general cholesterol / Hs-LPVP.

Atorvastatin reduces viscosity of a blood plasma and activity of some factors of coagulation and aggregation of thrombocytes. Thanks to it it improves a hemodynamics and normalizes a condition of coagulant system. HMG-CoA reductase inhibitors also have effect on metabolism of macrophages, block their activation and warn a rupture of an atherosclerotic plaque.

Drug is appointed at insufficient efficiency of a dietotherapy and other not pharmacological methods of treatment. Read according to this reference what drug analogs Atoris exist cheaper.

As a rule, the therapeutic effect of Atorisa® develops after 2 weeks of administration of drug, and the maximum effect is reached in 4 weeks.

Pharmacokinetics. Absorption of an atorvastatin of high, about 80% is soaked up from a GIT. Cmax approach time on average — 1–2 h. At women of Cmax is 20% higher, and the indicator of AUC is 10% lower. Distinction of pharmacokinetics on age and a floor insignificant also do not demand dose adjustment from patients.

At patients with alcoholic cirrhosis of Tmax norms are 16 times higher. Owing to intensive metabolism at the first passing through a liver bioavailability of an atorvastatin low (12%).

The average volume of distribution of an atorvastatin is equal to 381 l. More than 98% of an atorvastatin contact proteins of a blood plasma. Atorvastatin does not get through GEB. It is metabolized preferential in a liver under the influence of P450 3A4 cytochrome with formation pharmacological of active metabolites (orto-and parahydroxylated metabolites, beta oxidation products). These are active metabolites which cause about 70% of the inhibiting activity concerning GMG-KOA-reduktazy which remains 20–30 h.

T1/2 of an atorvastatin equals 14 h. It is removed generally with bile (is not exposed to the expressed enterohepatic recirculation, it is not removed during a hemodialysis). About 46% of an atorvastatin are removed through intestines and less than 2% — kidneys.

Indications to use:

Primary hypercholesterolemia (a heterozygous family and single hypercholesterolemia (the II type across Frederikson);

the combined (mixed) lipidemia (IIA and IIb types across Frederikson);

disbetalipoproteinemiya (the III type across Frederikson) (as addition to a diet);

family endogenous gipertriglitseridemiya (the IV type across Frederikson), resistant to a diet;

homozygous family hypercholesterolemia at insufficient efficiency of a dietotherapy and other not pharmacological methods of treatment;

prevention of cardiovascular diseases:

- primary prevention of cardiovascular complications at the patients without clinical signs of an ischemic heart disease but having several risk factors of its development: the age is more senior than 55 years, nicotine addiction, arterial hypertension, a diabetes mellitus, the low Hs-LPVP level in a blood plasma, genetic predisposition, in a t.ch.n a dislipidemiya background;

- secondary prevention of cardiovascular complications at patients with an ischemic heart disease for the purpose of decrease in total rate of mortality, a myocardial infarction, a stroke, repeated hospitalization concerning stenocardia and need for revascularization.

Route of administration and doses:

Prior to treatment of Atorisom® of the patient it has to be transferred to a hypolipidemic diet which needs to be observed during therapy by drug.

Inside, irrespective of meal, once (at any time, but in one and too time), every day.

The recommended initial dose — 10 mg daily. The dose of drug varies from 10 mg to 80 mg of 1 times a day and is selected taking into account the initial Hs-LPNP level, the purpose of therapy and individual therapeutic effect.

The therapeutic effect of Atorisa® develops in 2 weeks of administration of drug, and the maximum effect is reached in 4 weeks. Therefore the dose should not be changed earlier than in 4 weeks after the beginning of administration of drug.

At primary (heterozygous hereditary and polygenic) a hypercholesterolemia (IIA type) and the mixed lipidemia (IIb type) treatment begin with an initial dose 10 mg of 1 times a day which is increased in 4 weeks depending on reaction of the patient. The maximum daily dose — 80 mg.

At a homozygous hereditary hypercholesterolemia the initial dose is selected individually, depending on expressiveness of a disease. When using the maximum daily dose of 80 mg the most optimum effect was (once) noted.

Аторис® apply as additional therapy to other methods of treatment (plasma exchange) or as the main treatment if therapy by other methods is impossible.

For patients of advanced age, and also with diseases of kidneys of dose adjustment it is not required.

To patients with abnormal liver functions drug appoint with care in connection with delay of removal it from an organism. Control of clinical and laboratory indicators is in this situation necessary, and at identification of considerable pathological changes the dose has to be reduced, or treatment has to be stopped.

Features of use:

Before therapy of Atorisom® the patient needs to appoint a standard gipokholesterinemichesky diet which he has to observe during the entire period of treatment.

Increase in activity of liver enzymes in blood serum can be observed during treatment of Atorisom®. This increase, as a rule, small has also no clinical value. However control of activity of liver enzymes in blood serum before treatment, in 6 and 12 weeks is recommended and at increase in a dose of an atorvastatin. If triple increase in activity of ACT and/or ALT of rather upper bounds of norm is noted, treatment of Atorisom® has to be stopped. Atorvastatin can cause increase in activity of a kreatinfosfokinaza and aminotransferases.

At the women of reproductive age who are not using reliable contraception, use of Atorisa® is not recommended. If the patient plans pregnancy, it has to stop reception of Atorisa®, at least, a month before the planned pregnancy.

Treatment of Atorisom® can cause a myopathy which sometimes is followed rabdomiolizy, leading to an acute renal failure. The risk of this complication increases at a concomitant use with Atorisom® of one or several of the following medicines: derivatives of fibroyevy acid, Niacinum, cyclosporine, нефазодон, some antibiotics, antifungal means from group of azoles, inhibitors of HIV proteases.

Influence on ability to drive the car or to perform the works demanding the increased speed of physical and mental reactions. About adverse influence of Atorisa® on ability to drive the car and work with mechanisms it was not reported.

Side effects:

From TsNS and peripheral nervous system: headache, dizziness, asthenic syndrome, sleeplessness or drowsiness, dreadful dreams, amnesia, paresthesias, peripheral neuropathy, indisposition.

From sense bodys: sonitus, nasopharyngitis, nasal bleeding.

From cardiovascular system: heartbeat, vazodilatation, migraine, postural hypotension, increase in the ABP, phlebitis, arrhythmia.

From system of a hemopoiesis: thrombocytopenia.

From respiratory system: stethalgia.

From the alimentary system: nausea, dyspepsia, lock or diarrhea, meteorism, gastralgia, abdominal pain, anorexia or increase in appetite, pancreatitis, cholestatic jaundice, increase in activity of liver enzymes, hepatitis, disturbance of flavoring perception.

From a musculoskeletal system: mialgiya, arthralgia, dorsodynia, swelling of joints, myopathy, myotonia, miositis, рабдомиолиз, tendopatiya.

From urinogenital system: impotence, secondary renal failure.

From integuments: alopecia.

Allergic reactions: skin itch, skin rash, contact dermatitis, seldom urticaria, Quincke's disease, anaphylaxis, multiformny exudative erythema, Stephens-Johnson's syndrome, toxic epidermal necrolysis (Lyell's disease).

Laboratory indicators: hyperglycemia, hypoglycemia, increase in serumal KFK, increase in activity of ALT, ACT.

Others: peripheral hypostases, increase in body weight, increased fatigue, fever.

Interaction with other medicines:

Simultaneous use of an atorvastatin with cyclosporine, antibiotics (erythromycin, кларитромицин, kvinupristin/dalfopristin), HIV protease inhibitors (индинавир, ритонавир), antifungal means (флуконазол, итраконазол, кетоконазол) or with nefazodony can lead to increase in maintenance of an atorvastatin in blood serum that increases risk of emergence of a myopathy with rabdomiolizy and a renal failure. Similar interaction is possible at the combined reception of Atorisa® with derivatives of fibroyevy acid (fibratama) and Niacinum (niacin).

The concomitant use of an atorvastatin with Phenytoinum and rifampicin can lead to reduction of efficiency of an atorvastatin. At joint reception antacids (suspension of magnesium hydroxides and aluminum) reduce the maintenance of an atorvastatin in a blood plasma.

At a concomitant use of an atorvastatin with kolestipoly concentration of an atorvastatin in plasma goes down for 25%, but the therapeutic effect of a combination is higher, than effect of one atorvastatin.

Simultaneous use with the HP reducing concentration of endogenous steroid hormones (including Cimetidinum, ketokonazoly, Spironolactonum), increases risk of decrease in endogenous steroid hormones (it is necessary to be careful).

At the patients who are at the same time receiving 80 mg of an atorvastatin and digoxin, the content of digoxin increases in plasma approximately for 20%. The patients receiving аторвастатин with digoxin should be observed.

At joint reception of an atorvastatin with oral contraceptives (norethindrone and ethinylestradiol) strengthening of absorption of contraceptives and increase in their concentration in a blood plasma is possible. It is necessary to control the choice of contraceptives at the women receiving аторвастатин.

The concomitant use of an atorvastatin with warfarin can strengthen in the first days effect of warfarin on blood coagulation indicators (reduction of PV). This effect disappears after 15 days of joint reception of the specified drugs.

Cimetidinum — there is no clinically significant interaction.

The concomitant use with inhibitors of proteases leads to increase in concentration of an atorvastatin in a blood plasma.

The grapefruit juice use during treatment of Atorisom® can lead to increase in concentration of drug in a blood plasma. In this regard the patients accepting Atoris® have to avoid the use of this juice more than 1,2 l a day.

Contraindications:

Hypersensitivity to any of drug components;

liver diseases in an active stage (including active chronic hepatitis, chronic alcoholic hepatitis);

liver failure;

cirrhosis of any etiology;

increase in activity of hepatic transaminases of not clear genesis more than by 3 times in comparison with VGN;

diseases of skeletal muscles;

pregnancy and the period of a lactation, and also use for the women of reproductive age who are not using adequate methods of contraception;

age up to 18 years (efficiency and safety of use are not established);

galactosemia (since drug contains lactose) or syndrome of the broken absorption of a glucose/galactose, deficit of lactase.

With care: alcoholism, liver diseases in the anamnesis.

Use at pregnancy and feeding by a breast

Atorvastatin is contraindicated to use for pregnant women and nursing mothers. Drug is appointed to women of reproductive age only if probability of pregnancy at them very low, and the patient is informed on possible risk for a fruit. Women of reproductive age during treatment have to use adequate methods of contraception.

In need of purpose of Atorisa® it is necessary to resolve an issue of the breastfeeding termination.

Overdose:

Symptoms: at development of a myopathy with the subsequent rabdomioliz and an acute renal failure (rare, but heavy side effect) drug has to be immediately cancelled.

Treatment: the patient needs to enter diuretic and solution of Natrii hydrocarbonas. If necessary it is necessary to carry out a hemodialysis. Rabdomioliz can lead to a hyperpotassemia which elimination requires intravenous administration of Calcii chloridum or calcium of a gluconate, infusion of glucose with insulin, use of exchangers of potassium ions or, in hard cases, carrying out a hemodialysis. As аторвастатин it is substantially connected with proteins of a blood plasma, the hemodialysis is rather ineffective way of removal of this substance from an organism.

General actions: monitoring and maintenance of vital signs and prevention of further absorption of drug (gastric lavage, purpose of absorbent carbon or purgatives).