ATORIS PILLS 10MG

ATORIS TAB. P / O 10MG №90

Film Coated Tablets white, round, slightly biconvex, on fracture - white mass with a rough surface.

Excipients:Povidone, sodium lauryl sulfate, calcium carbonate, microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, Magnesium stearate.

Shell composition: Opadry II HP 85F28751 white (polyvinyl alcohol, titanium dioxide (E171), macrogol 3000, talc).

10 pieces. - blisters (1) - packs cardboard.
10 pieces. - blisters (3) - packs cardboard.
10 pieces. - blisters (9) - packs cardboard.

Film Coated Tablets white, round, slightly biconvex, on fracture - white mass with a rough surface.

Excipients:Povidone, sodium lauryl sulfate, calcium carbonate, microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate.

Shell composition: Opadry II HP 85F28751 white (polyvinyl alcohol, titanium dioxide (E171), macrogol 3000, talc).

10 pieces. - blisters (1) - packs cardboard.
10 pieces. - blisters (3) - packs cardboard.
10 pieces. - blisters (9) - packs cardboard.

Film Coated Tablets white or almost white, round, slightly biconvex.

Excipients:Povidone, sodium lauryl sulfate, calcium carbonate, microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate.

Shell composition: Opadry White Y-1-7000 (hypromellose, titanium dioxide (E171), macrogol 400).

10 pieces. - blisters (1) - packs cardboard.
10 pieces. - blisters (3) - packs cardboard.
10 pieces. - blisters (9) - packs cardboard.

Clinico-pharmacological group

Lipid-lowering drug

Mechanism of action

Lipid-lowering drug from the group of statins.

The main mechanism of action of Atorvastatin is the inhibition of the activity of HMG-CoA reductase, an enzyme catalyzing the conversion of HMG-CoA to mevalonic acid. This transformation is one of the early stages in the chain of cholesterol synthesis (Xc) in the body. Suppression of Xc synthesis leads to increased reactivity of LDL receptors in the liver and extrahepatic tissues. These receptors bind the LDL particles and remove them from the blood plasma, which leads to a decrease in the level of Xc-LDL in the blood.

Anti-atherosclerotic effect of the drug is manifested by the effect of atorvastatin on the walls of blood vessels and blood components. Atorvastatin inhibits the synthesis of isoprenoids, which are growth factors for the inner lining of blood vessels. Under the influence of atorvastatin, the endothelium-dependent dilation of blood vessels is improved. Atorvastatin reduces the total XC, LDL, apolipoprotein B, TG. Causes an increase in the content of HD-C and HDL and apolipoprotein A.

The effect of Atoris develops 2 weeks after the start of the drug, the maximum effect is achieved after 4 weeks.

Pharmacokinetics

Suction

After ingestion is well absorbed from the gastrointestinal tract (80%). Time to reach Cmax is 1-2 hours

Due to intensive metabolism during the "first pass" through the liver, atorvastatin bioavailability is 12%.

Distribution

Medium Vd - 381 l, binding to plasma proteins - 98%. Atorvastatin does not penetrate the BBB.

Metabolism

It is metabolized mainly in the liver under the action of cytochrome P450 3A4 with the formation of pharmacologically active metabolites (ortho and parahydroxylated derivatives, beta-oxidation products). These active metabolites account for approximately 70% of the inhibitory activity against HMG-CoA reductase, which persists for 20-30 hours.

Removal

It is mainly excreted in the bile (it does not undergo a pronounced enterohepatic recirculation). T1/2 - 14 hours. About 46% is excreted in the feces, less than 2% - in the urine.

Pharmacokinetics in special clinical situations

Cmax women higher by 20%, AUC - lower by 10%.

Cmax in patients with alcoholic cirrhosis of the liver is 16 times higher than normal.

Indications for use of the drug

- to reduce serum levels of total Xc, Xc-LDL, apolipoprotein B and triglycerides in patients with primary hyperlipidemia (types IIa and IIb by Fredrickson), familial heterozygous hypercholesterolemia and mixed hyperlipidemia;

- to reduce elevated levels of total Xc, Xc-LDL and apolipoprotein B in blood plasma in patients with homozygous familial hypercholesterolemia.

Atorvastatin increases serum levels of Xc-HDL and decreases the ratios of Xc-LDL / Xc-HDL and total Xc / Xc-HDL.The drug is prescribed with insufficient efficacy of diet therapy and other non-pharmacological treatment methods.

Dosage and administration

Prior to the initiation of treatment by Atoris, the patient should be transferred to a lipid-lowering diet, which must be followed during drug therapy.

The drug is taken orally, regardless of the meal.

The recommended starting dose is 10 mg daily. The dose of the drug varies from 10 mg to 80 mg 1 time / day, selected based on the initial level of LDL-C, the goal of therapy and individual therapeutic effect. The drug can be taken in another registered dosage (in the form of film-coated tablets, 40 mg). Atoris® take once at any time of the day, but at the same time every day.

Therapeutic effect of Atoris is noted after 2 weeks of taking the drug, the maximum effect is achieved after 4 weeks. Therefore, the dose should not be changed earlier than 4 weeks after starting the drug.

At the beginning of therapy and / or during the dose increase, it is necessary to control the content of plasma lipids every 2–4 weeks and adjust the dose accordingly.

Atprimary (heterozygous hereditary and polygenic) hypercholesterolemia (type IIa) and mixed hyperlipidemia (type IIb) Treatment begins with the recommended initial dose, which is increased after 4 weeks, depending on the response of the patient. The maximum daily dose is 80 mg.

Athomozygous hereditary hypercholesterolemiaThe initial dose is adjusted individually depending on the severity of the disease.In most patients, the optimal effect was observed when using the drug in a daily dose of 80 mg (1 time / day). Atoris® used as an additional therapy to other methods of treatment (plasmapheresis) or as the main method of treatment, if therapy by other methods is impossible.

Forelderly patients and patients with impaired renal function dose adjustment is not required.

does not affect the level of atorvastatin in the blood plasma or the degree of decrease in the content of Xc-LDL when using atorvastatin, therefore, changing the dose of the drug is not required.

the drug is prescribed with caution in connection with the slowing down of the drug from the body. In this situation, control of clinical and laboratory parameters is shown, and if significant pathological changes are detected, the dose should be reduced or treatment should be discontinued.

Side effect

Nervous system: insomnia or drowsiness, dizziness, headache, asthenic syndrome, nightmares, amnesia, paresthesias, peripheral neuropathy, emotional lability, ataxia, hyperkinesis, depression, hypesthesia, weakness, malaise.

Special senses: amblyopia, tinnitus, dry conjunctiva, accommodation disturbance, hemorrhage in the eyes, deafness, glaucoma, parosmia, loss of taste.

Since the cardiovascular system: palpitations, vasodilation, migraine, postural hypotension, increased blood pressure, phlebitis, arrhythmia, chest pain, vasculitis.

From the hemopoietic system: anemia, lymphadenopathy, thrombocytopenia.

On the part of the respiratory system: bronchitis, rhinitis, dyspnea, bronchial asthma, epistaxis.

From the digestive system: nausea, heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, anorexia, increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, gastroenteritis, hepatitis, hepatic colic, cheilitis, hepatitis, hepatitis, gastroenteritis, hepatitis, hepatic colic, cheilitis, jaundice , cholestatic jaundice, increased activity of hepatic transaminases, rectal bleeding, melena, gingival bleeding, tenesmus.

From the musculoskeletal system: arthritis, leg muscle cramps, bursitis, myositis, myopathy, arthralgia, muscle weakness, myalgia, rhabdomyolysis, joint contractures, rheumatic polymyalgia, back pain.

From the genitourinary system: urogenital infections, dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, urgency to urinate), cystitis, hematuria, vaginal bleeding, uterine bleeding, urolithiasis, metrorrhagia, epididymitis, decreased libido, impotence, ejaculation disorder .

Dermatological reactions: sweating, eczema, seborrhea, ecchymosis.

Allergic reactions: pruritus, skin rash, contact dermatitis; rarely, urticaria, angioedema, facial edema, lupus-like syndrome, vasculitis, photosensitivity, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

From the laboratory indicators: hyperglycemia, hypoglycemia, increased serum CPK, albuminuria, increased activity of ALT, AST, thrombocytopenia, eosinophilia, increased ESR.

Other: peripheral edema, weight gain, gynecomastia, exacerbation of gout, fever, alopecia.

Contraindications to the use of the drug

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

- liver failure;

- cirrhosis of the liver of various etiologies;

- increased activity of hepatic transaminases of unclear genesis;

- diseases of skeletal muscles;

- pregnancy;

- lactation period (breastfeeding);

- age up to 18 years (efficacy and safety of use has not been established);

- hypersensitivity to the drug.

The drug is not prescribed to women of reproductive age who do not use adequate methods of contraception.

The drug contains lactose, therefore it is not recommended for patients with galactosemia or syndrome of impaired glucose / galactose absorption, lactase deficiency.

WITHcaution It should appoint a drug for alcoholism, liver disease in history.

Use of the drug during pregnancy and lactation

Atorvastatin is contraindicated for use in pregnant and nursing mothers.

Drug is prescribedwomen of reproductive age only if the probability of pregnancy is very low and the patient is informed of the possible risk to the fetus. Women of reproductive age during treatment should use adequate methods of contraception. If a woman is planning a pregnancy, she should stop taking Atoris at least a month before the planned pregnancy.

If necessary, the appointment of Atoris should decide on the termination of breastfeeding.

Application for violations of the liver

The drug is contraindicated in liver diseases in the active stage (including active chronic hepatitis, chronic alcoholic hepatitis); liver failure; in case of liver cirrhosis of various etiologies; with increased activity of hepatic transaminases of unknown origin

Application for violations of kidney function

does not affect the level of atorvastatin in the blood plasma or the degree of decrease in the content of Xc-LDL when using atorvastatin, therefore, changing the dose of the drug is not required.

special instructions

Before starting treatment with Atoris, the patient should be prescribed a standard cholesterol-lowering diet, which he must follow during the entire period of treatment.

When using Atoris, there may be an increase in liver transaminase activity.This increase is usually small and has no clinical significance. However, it is necessary to regularly monitor indicators of liver function before starting treatment, after 6 weeks and 12 weeks after starting the use of the drug and after increasing the dose. Treatment should be discontinued with an increase in AST and ALT more than 3 times relative to VGN.

Atorvastatin can cause an increase in the activity of CPK and aminotransferases.

Patients should be warned that they should immediately consult a doctor if they develop unexplained pain or muscle weakness. Especially if these symptoms are accompanied by malaise and fever.

When treating Atoris, myopathy may develop, sometimes accompanied by rhabdomyolysis, leading to acute renal failure . The risk of this complication increases when one or more of the following drugs are taken with Atoris at the same time: fibrates, nicotinic acid, cyclosporine, nefazodone, some antibiotics, antifungals from the group of azoles, HIV protease inhibitors. In clinical manifestations of myopathy, it is recommended to determine plasma concentrations of CPK. With a 10-fold increase in VGN of CPK activity, Atoris treatment should be discontinued.

There are reports of the development of atonic fasciitis on the background of the use of atorvastatin, however, the connection with the use of the drug is possible, but to date has not been proven, the etiology is not known.

Influence on ability to drive motor transport and control mechanisms

No adverse effect of Atoris on the ability to drive motor vehicles and control mechanisms was reported.

Overdose

Treatment: in case of overdose, the following general measures are necessary: ​​monitoring and maintaining vital functions, and preventing further absorption of the drug (gastric lavage, taking Activated carbon or laxatives). There is no specific antidote.

With the development of myopathy with subsequent rhabdomyolysis and acute renal failure (a rare but severe side effect), the drug should be immediately canceled, and the patient must enter a diuretic and sodium bicarbonate solution. If necessary, hemodialysis should be carried out.

Rhabdomyolysis can lead to hyperkalemia, which requires iv administration of calcium chloride or Calcium gluconate , infusion of glucose with insulin , the use of potassium ion exchangers or, in severe cases, hemodialysis.

Since atorvastatin is largely bound to plasma proteins, hemodialysis is a relatively inefficient way to remove this substance from the body.

Drug interaction

With simultaneous use of atorvastatin with cyclosporine, HIV protease inhibitors (indinavir, ritonavir), antibiotics (erythromycin, Clarithromycin , quinupristin / dalfopristin), antifungal drugs from the group of azoles (fluconazole,Itraconazole, ketoconazole), nefazodone, derivatives of fibric acid, nicotinic acid, plasma atorvastatin concentration increases, which increases the risk of myopathy with rhabdomyolysis and acute renal failure.

With simultaneous use with Erythromycin CmaxAtorvastatin is increased by 40%.

Simultaneous use of atorvastatin with phenytoin can lead to a decrease in the effectiveness of atorvastatin.

With the joint use of antacids (suspension of hydroxides of magnesium and aluminum) reduce the content of atorvastatin in the blood plasma.

At the same time taking atorvastatin with colestipol, the concentration of atorvastatin in plasma decreases by 25%, but the therapeutic effect of the combination is higher than the effect of a single drug.

Simultaneous use with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, Ketoconazole , spironolactone) increases the risk of reducing endogenous steroid hormones (caution should be exercised).

In patients simultaneously receiving atorvastatin at a dose of 80 mg and Digoxin , the content of digoxin in the plasma increases by about 20%. Patients receiving this combination should be under the supervision of a physician.

With simultaneous use with oral contraceptives (a combination of norethisterone and ethinyl estradiol) may increase the absorption of contraceptives and increase their concentrations in the blood plasma.Therefore, it is necessary to control the choice of contraceptives in women receiving atorvastatin.

Simultaneous intake of atorvastatin with Warfarin may increase the effect of warfarin on blood coagulation rates in the first days (reduction of prothrombin time). This effect disappears after 15 days of taking these drugs at the same time.

The simultaneous use of atorvastatin with protease inhibitors is accompanied by an increase in plasma atorvastatin concentration.

Clinically significant interaction with cimetidine is not observed.

The use of grapefruit juice in the treatment of Atoris can lead to an increase in plasma atorvastatin concentrations. In this regard, patients taking Atoris®should avoid drinking this juice.

Pharmacy sales terms

The drug is available on prescription.

Terms and conditions of storage

List B. The drug should be kept out of the reach of children at a temperature not exceeding 25 ° C. Shelf life - 2 years.