Atorvastatin

General characteristics. Structure:

Active ingredient: 10 mg or 20 mg of an atorvastatin.

Excipients: cellulose microcrystallic, starch corn prezhelatinizirovanny, silicon dioxide colloid, magnesium carbonate, magnesium stearate.

Structure of a cover of a tablet: опадрай the II white (85F18422), (polyvinyl alcohol - 40%, titanium dioxide - 25%, a macrogoal-3350 - 20.2%, talc - 14.8%).

Pharmacological properties:

Pharmacodynamics. Hypolipidemic means from group of statines. By the principle of competitive antagonism the molecule of statine contacts that part of a receptor of coenzyme A where GMG-KOA-reduktaza is attached. Other part of a molecule of statine inhibits process of transformation of hydroxymethylglutarate in мевалонат, an intermediate product in synthesis of a molecule of cholesterol. The inhibition of activity of GMG-KOA-reduktazy leads to a series of consecutive reactions as a result of which the intracellular content of cholesterol decreases and there is a compensatory increase in activity of LPNP-receptors and respectively acceleration of a catabolism of cholesterol (Xc) of LPNP.

The hypolipidemic effect of statines is connected with decrease in level of general Hs at the expense of Hs-LPNP. Decrease in the LPNP level is dozozavisimy and has not linear, but exponential character. The inhibiting effect of an atorvastatin concerning GMG-KOA-reduktazy approximately is defined on 70% by activity of its circulating metabolites.

Statines do not influence activity of lipoprotein and gepatichesky lipases, have no significant effect on synthesis and a catabolism of free fatty acids therefore their influence on the TG level for the second time and is mediated through their main effects on decrease in the Hs-LPNP level. Moderate decrease in the TG level at treatment by statines, apparently, is connected with an expression remnantny (апо E) receptors on the surface of the hepatocytes participating in a catabolism of LPPP, as a part of which about 30% of TG. In comparison with other statines (except for a rozuvastatin) аторвастатин causes more expressed decrease in the TG level.

In addition to hypolipidemic action, statines exert positive impact at endothelium dysfunction (a preclinical symptom of early atherosclerosis), on a vascular wall, a condition of an atheroma, improve rheological properties of blood, have antioxidant, anti-proliferative properties.

Atorvastatin reduces cholesterol level at patients with a homozygous family hypercholesterolemia which usually does not give in to therapy by hypolipidemic means.

Pharmacokinetics. Atorvastatin is quickly absorbed from a GIT. Absolute bioavailability low - about 12% that is caused by presistemny clearance in a mucous membrane of a GIT and/or owing to "the first passing" through a liver, is preferential in the scene of action.

Atorvastatin is metabolized with the participation of CYP3A4 isoenzyme with formation of a number of substances which are GMG-KOA-reduktazy inhibitors.

T1/2 makes about 14 h of plasma though T1/2 of inhibitor of activity of GMG-KOA-reduktazy makes about 20-30 h that is caused by participation of active metabolites.

Linkng with proteins of plasma makes 98%. Atorvastatin is brought in the form of metabolites preferential with bile.

Indications to use:

Primary hypercholesterolemia at inefficiency of a dietotherapy, the combined hypercholesterolemia and a gipertriglitseridemiya, a heterozygous and homozygous family hypercholesterolemia at inefficiency of a dietotherapy.

Route of administration and doses:

Treatment is carried out against the background of a standard diet for patients with a hypercholesterolemia. The dose is established individually, depending on the initial level of cholesterol. Accept inside. The initial dose usually makes 10 mg of 1 times/days. The effect is shown within 2 weeks, and the maximum effect - within 4 weeks. If necessary it is possible to increase a dose gradually with an interval of 4 weeks and more. The maximum daily dose - 80 mg.

Features of use:

Use at pregnancy and feeding by a breast. Atorvastatin is contraindicated to use at pregnancy and in the period of a lactation (breastfeeding).

It is unknown whether it is allocated аторвастатин with breast milk. Considering a possibility of the undesirable phenomena at babies, in need of use of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Women of reproductive age during treatment have to use adequate methods of contraception. Atorvastatin it is possible to apply at women of reproductive age only if probability of pregnancy very low, and the patient is informed on possible risk of treatment for a fruit.

Use at abnormal liver functions. Contraindication: liver diseases in an active stage.

Prior to the beginning of and during treatment atorvastatiny, especially at emergence of symptoms of damage of a liver, it is necessary to control indicators of function of a liver. At increase in level of transaminases their activity should be controlled up to normalization. If activity of nuclear heating plant or ALT, more than by 3 times exceeding norm, remains, recommended a dose decline or cancellation of an atorvastatin.

Use for children. At children experience of use of an atorvastatin in a dose to 80 mg/days is limited.

Special instructions. Prior to the beginning of and during treatment atorvastatiny, especially at emergence of symptoms of damage of a liver, it is necessary to control indicators of function of a liver. At increase in level of transaminases their activity should be controlled up to normalization. If activity of nuclear heating plant or ALT, more than by 3 times exceeding norm, remains, recommended a dose decline or cancellation of an atorvastatin.

At emergence against the background of treatment of symptoms of a myopathy it is necessary to define activity of KFK. If substantial increase of the KFK level remains, then it is recommended to lower a dose or to cancel аторвастатин.

The risk of a myopathy during treatment atorvastatiny increases at simultaneous use of cyclosporine, fibrat, erythromycin, the antifungal drugs relating to azoles and Niacinum.

There is a probability of development of the following side reactions, however not in all cases accurate connection with reception of an atorvastatin is established: myotonia, miositis, myopathy, paresthesia, peripheral neuropathy, pancreatitis, hepatitis, cholestatic jaundice, anorexia, vomiting, alopecia, itch, rash, impotence, hyperglycemia and hypoglycemia.

At children experience of use of an atorvastatin in a dose to 80 mg/days is limited.

With care apply аторвастатин at patients with an alcoholism.

Side effects:

From a nervous system:> 1% - sleeplessness, dizziness; <1% - a headache, an adynamy, an indisposition, drowsiness, dreadful dreams, paresthesias, a peripheral neuropathy, amnesia, emotional lability, an ataxy, paralysis of a facial nerve, hyperkinesias, migraine, a depression, a hypesthesia, a loss of consciousness.

From sense bodys: <1% - an amblyopia, a ring in ears, dryness of a conjunctiva, accommodation disturbance, hemorrhage in a mesh cover of an eye, deafness, glaucoma, a parosmiya, loss of flavoring feelings, a food faddism.

From cardiovascular system:> 1% - a stethalgia; <1% - heartbeat, vazodilatation symptoms, orthostatic hypotension, increase in the ABP, phlebitis, arrhythmia, stenocardia.

From system of a hemopoiesis: <1% - anemia, a limfoadenopatiya, thrombocytopenia.

From respiratory system:> 1% - bronchitis, rhinitis; <1% - pneumonia, диспноэ, an exacerbation of bronchial asthma, nasal bleeding.

From the alimentary system:> 1% - nausea; <1% - heartburn, a lock or diarrhea, a meteorism, a gastralgia, an abdominal pain, decrease or increase in appetite, dryness in a mouth, an eructation, a dysphagy, vomiting, stomatitis, an esophagitis, a glossitis, erosive cankers of a mucous membrane of an oral cavity, a gastroenteritis, hepatitis, bilious colic, a cheilitis, a duodenum ulcer, pancreatitis, cholestatic jaundice, an abnormal liver function, rectal bleeding, a melena, bleeding of gums, tenesmus.

From a musculoskeletal system:> 1% - arthritis; <1% - myotonia of legs, a bursitis, tendosinovit, a miositis, a myopathy, arthralgias, a mialgiya, рабдомиолиз, a wryneck, a muscle hyper tone, contractures of joints, puffiness of joints, a tendopatiya (in certain cases with a rupture of sinews).

From urinogenital system:> 1% - urogenital infections, peripheral hypostases; <1% - a dysuria (including a pollakiuria, a nocturia, an incontience of urine or a delay of an urination, imperative desires on an urination), a leukocyturia, nephrite, a hamaturia, vaginal bleeding, нефроуролитиаз, a metrorrhagia, an epididymite, decrease in a libido, impotence, disturbance of an ejaculation.

Dermatological reactions:> 1% - an alopecia, a xerodermia, a photosensitization, the increased sweating, eczema, seborrhea, ecchymomas, petechias.

From endocrine system: <1% - a gynecomastia, a mastodynia.

From a metabolism: <1% - increase in body weight, an exacerbation of gout.

Allergic reactions: <1% - a skin itch, skin rash, contact dermatitis, is rare - a small tortoiseshell, a Quincke's disease, a face edema, an anaphylaxis, a mnogoformny exudative erythema (including Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease).

Laboratory indicators: <1% - a hyperglycemia, a hypoglycemia, increase in serumal KFK, an albuminuria.

Interaction with other medicines:

At simultaneous use of an atorvastatin with digoxin concentration of digoxin in a blood plasma slightly increases.

Diltiazem, verapamil, израдипин inhibit an isoenzyme of CYP3A4 which participates in metabolism of an atorvastatin therefore at simultaneous use with these blockers of calcium channels increase in concentration of an atorvastatin in a blood plasma and increase in risk of development of a myopathy is possible.

At simultaneous use of an itrakonazol concentration of an atorvastatin in a blood plasma, apparently, owing to inhibition itrakonazoly his metabolism in a liver which happens with the participation of CYP3A4 isoenzyme considerably increases; increase in risk of development of a myopathy.

At simultaneous use of a kolestipol reduction of concentration of an atorvastatin in a blood plasma is possible, at the same time the hypolipidemic effect amplifies.

At simultaneous use the antacids containing magnesium hydroxide and aluminum hydroxide reduce concentration of an atorvastatin approximately by 35%.

At simultaneous use of cyclosporine, fibrat (including gemfibrozit), antifungal drugs of derivatives of an azol, niacin the risk of development of a myopathy increases.

At simultaneous use of erythromycin, a klaritromitsin concentration of an atorvastatin in plasma moderately increases, the risk of development of a myopathy increases.

At simultaneous use of ethinylestradiol, Norethisteronum (norethindrone) concentration of ethinylestradiol, Norethisteronum and (norethindrone) in a blood plasma slightly increases.

At simultaneous use of inhibitors of proteases concentration of an atorvastatin in a blood plasma since inhibitors of proteases are CYP3A4 isoenzyme inhibitors increases.

Contraindications:

Liver diseases in an active stage, increase in activity of transaminases of serum more than by 3 times of not clear genesis, pregnancy, a lactation (breastfeeding), the women of reproductive age who are not applying well-tried remedies of contraception; hypersensitivity to an atorvastatin.

Issue conditions:

According to the recipe

Packaging:

On 30 tablets in blister strip packagings and in cardboard packs.