Atoris

Active material: Atorvastatin
When ATH: C10AA05
CCF: Lipid-lowering drugs
ICD-10 codes (testimony): E78.0, E78.2
When CSF: 16.01.01
Manufacturer: KRKA d.d. (Slovenia)

DOSAGE FORM, COMPOSITION AND PACKAGING

Pills, Film-coated white, round, slightly biconcave, of presentations – white mass with a rough surface.

Excipients: povidone, sodium lauryl, calcium carbonate, microcrystalline cellulose, lactose monohydrate, Croscarmellose sodium, magnesium stearate.

The composition of the shell: Opadry II HP 85F28751 white (polyvinyl alcohol, Titanium dioxide (E171), macrogol 3000, talc).

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.

Pills, Film-coated white, round, slightly biconcave, of presentations – white mass with a rough surface.

Excipients: povidone, sodium lauryl, calcium carbonate, microcrystalline cellulose, lactose monohydrate, Croscarmellose sodium, magnesium stearate.

The composition of the shell: Opadry II HP 85F28751 white (polyvinyl alcohol, Titanium dioxide (E171), macrogol 3000, talc).

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.

Pills, Film-coated white or nearly white, round, slightly biconcave.

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

The composition of the shell: Opadry White Y-1-7000 (gipromelloza, Titanium dioxide (E171), macrogol 400).

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.

Pharmacological action

Lipid-lowering drugs of the statin.

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

Anti-atherosclerotic effect of the drug is the influence of atorvastatin on the walls of blood vessels and blood components. Atorvastatin inhibits the synthesis of isoprenoid, It is a growth factor inner lining of blood vessels. Under the influence of atorvastatin improves endothelium-dependent vasodilation. Atorvastatin reduces the total cholesterol, LDL, apolipoprotein B, TG. It causes increase of HDL-C and apolipoprotein A.

Action Atoris^® develops through 2 weeks after the start of dosing, maximum effect is achieved after 4 of the week.

Pharmacokinetics

Absorption

After ingestion well absorbed from the gastrointestinal tract (80%). The time to reach C_max is 1-2 no.

Due to intensive metabolism in “first pass” through the liver bioavailability of atorvastatin 12%.

Distribution

Average V_d – 381 l, Plasma protein binding - 98%. Atorvastatin did not penetrate the BBB.

Metabolism

It is metabolized primarily in the liver by the action of cytochrome P450 3A4 to produce pharmacologically active metabolites (ortho- paragidroksilirovannyh and derivatives, beta-oxidation products). This active metabolites are responsible for about 70% inhibitory activity against HMG-CoA reductase, which persists 20-30 no.

Deduction

Write mainly in the bile (It does not undergo pronounced enterohepatic recirculation). T_1/2 – 14 no. About 46% excreted in the feces, less 2% – urine.

Pharmacokinetics in special clinical situations

C_max women up 20%, AUC - below 10%.

C_max in patients with alcoholic cirrhosis 16 times higher than normal.

Testimony

- To reduce the serum levels of total cholesterol, LDL-C, apolipoprotein B and triglyceride levels in patients with primary hyperlipidemia (Types IIa and IIb of Fredrickson), heterozygous familial hypercholesterolemia and mixed hyperlipidemia;

- To reduce the elevated plasma levels of total cholesterol, LDL-C, and apolipoprotein B in patients with homozygous familial hypercholesterolemia.

Atorvastatin increases the serum levels of LDL-LPVN and reduces the value of the ratio of LDL-C / HDL-C and total cholesterol / HDL-C. The drug is prescribed for lack of effectiveness of diet therapy and other non-pharmacological treatments.

Dosage regimen

Prior to treatment Atoris^® the patient should be transferred to the lipid-lowering diet, which must be observed during drug therapy.

The drug is taken orally, regardless of the meal.

The recommended starting dose – 10 mg daily. Dose ranges from 10 mg 80 mg 1 time / day, selected with the baseline LDL-C, goals of therapy and individual therapeutic effect. You can receive the drug registered in another dosage (in the form of tablets, film-coated, 40 mg). Atoris^® take once at any time of the day, but at the same time each day.

The therapeutic effect Atoris^® observed after 2 week dosing, maximum effect is achieved after 4 of the week. Therefore, the dose should not be changed sooner than 4 weeks after the start of dosing.

At the beginning of therapy and / or during increasing doses needed every 2-4 week control lipid content in the blood plasma and the dose adjusted accordingly.

At primary (heterozygous hereditary and polygenic) hypercholesterolemia (type IIa) and mixed hyperlipidemia (TYPE IIb) treatment is initiated with a recommended starting dose, which increased after 4 weeks depending on the response of the patient. The maximum daily dose – 80 mg.

At Homozygous Familial Hypercholesterolemia the initial dose is selected individually depending on the severity of the disease. In most patients, the optimum effect observed using the preparation in a daily dose of 80 mg (1 time / day). Atoris^® used as an adjunct to other therapies (plasmapheresis) or as the primary method of treatment, if other methods of treatment can not be.

To elderly patients and patients with impaired renal function dose adjustment is required.

Impaired renal function It has no effect on the level of atorvastatin plasma or degree reduction of LDL-C in applying atorvastatin, therefore change the dose is not required.

Patients with impaired hepatic function the drug is prescribed with caution due to the slowdown of the body's Withdrawal. This situation illustrates the control of clinical and laboratory parameters and the detection of significant lesions dose should be reduced or treatment should be discontinued.

Side effect

From the central and peripheral nervous system: insomnia or drowsiness, dizziness, headache, asthenic syndrome, nightmares, amnesia, paresthesia, perifericheskaya neuropathy, emotional lability, ataxia, hyperkinesis, depression, gipesteziya, weakness, malaise.

From the senses: amblyopia, tinnitus, dryness of the conjunctiva, ccomodation, bleeding in the eye, deafness, glaucoma, parosmija, loss of taste.

Cardio-vascular system: heartbeat, vasodilation, migraine, postural hypotension, increased blood pressure, phlebitis, arrhythmia, chest pain, vasculitis.

From the hematopoietic system: anemia, lymphadenopathy, thrombocytopenia.

The respiratory system: bronchitis, rhinitis, dyspnoea, bronchial asthma, nose bleed.

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, pečenočnaâ how, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, increase in liver transaminases, rectal bleeding, ground, krovotochivosty right, tenesmus.

On the part of the musculoskeletal system: arthritis, cramping of the leg muscles, ʙursit, myositis, myopathy, artralgii, muscular weakness, myalgia, raʙdomioliz, joint contractures, polymyalgia rheumatica, backache.

With the genitourinary system: urogenital infections, dizurija (incl. thamuria, nocturia, urinary incontinence or urinary retention, urgent need to urinate), cystitis, hematuria, vaginal bleeding, uterine bleeding, urolithiasis disease, metrorragija, epididymitis, decreased libido, impotence, abnormal ejaculation.

Dermatological reactions: Sweating, eczema, seborrhea, ecchymosis.

Allergic reactions: itching, skin rash, contact dermatitis; rarely - urticaria, angioedema, swelling of the face, lupus-like syndrome, vasculitis, photosensitivity, anaphylaxis, erythema multiforme exudative, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

From the laboratory parameters: giperglikemiâ, gipoglikemiâ, Increase serum CPK, albuminuria, increased ALT, IS, thrombocytopenia, eozinofilija, increased erythrocyte sedimentation rate.

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

Contraindications

- Liver disease in active phase (incl. chronic active hepatitis, chronic alcoholic hepatitis);

- Liver failure;

- Cirrhosis of various etiologies;

- Increase in liver transaminases of unknown origin;

- Diseases of skeletal muscle;

- Pregnancy;

- Lactation (breast-feeding);

- Up to 18 years (efficacy and safety have not been established);

- Hypersensitivity to the drug.

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

The drug contains lactose, It is therefore not recommended in patients with galactosemia and malabsorption syndrome glucose / galactose, lactase deficiency.

FROM caution should be prescribed the drug for alcoholism, a history of liver disease.

Pregnancy and lactation

Atorvastatin is contraindicated in pregnant women and nursing mothers. The drug is prescribed women of reproductive age only, if the probability of pregnancy have a very low, and the patient informed of the potential risk to the fetus. Women of childbearing age during treatment should use adequate contraception methods. If a woman is planning to become pregnant, she should stop taking Atoris^®, at least, a month before the planned pregnancy.

The appointment Atoris^® should decide the issue of termination of breastfeeding.

Cautions

Before therapy Atoris^® the patient must assign a standard hypocholesterolemic diet, which he must comply during the entire treatment period.

When using Atoris^® can be observed increase in liver transaminases. This increase, usually, small and has no clinical significance. However, it should regularly monitor liver function before treatment, through 6 weeks 12 weeks after starting the drug and then increase the dose. Treatment should be stopped if increased rates of AST and ALT more than 3 raza about VGN.

Atorvastatin can cause an increase in CPK and transaminases.

Patients should be warned about, they should immediately consult a doctor if you have unexplained pain or weakness in muscles. Especially, If these symptoms are accompanied by malaise and fever.

When treating Atoris^® may develop myopathy, which is sometimes accompanied by rhabdomyolysis, which leads to acute renal failure. The risk of this complication increases with simultaneous admission to the Atoris^® one or more of the following drugs: fibrates, a nicotinic acid, cyclosporine, nefazodon, certain antibiotics, antifungal agents from the group of azoles, HIV protease inhibitors. When clinical manifestations of myopathy is recommended to determine plasma concentrations of CK. With a 10-fold increase in the activity of CK treatment ULN Atoris^® It should be discontinued.

There are reports on the development of atopic fasciitis during treatment with atorvastatin, However, connection with use of the drug is possible, but to date has not been proven, etiology is unknown.

Effects on ability to drive vehicles and management mechanisms

The adverse impact Atoris^® on the ability to drive vehicles and management mechanisms have been reported.

Overdose

Treatment: in the event of an overdose, the following general measures: monitoring and maintenance of vital functions, and the prevention of further absorption of the drug (gastric lavage, administration of activated charcoal or laxatives). No specific antidote.

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

Rhabdomyolysis can lead to hyperkalemia, which is required to eliminate the in / in a calcium chloride or calcium gluconate, infusion glyukozы with insulinorna, the use of potassium ion exchangers or, in severe cases, hemodialysis.

Since atorvastatin significantly associated with plasma proteins, Hemodialysis is a relatively inefficient way to remove this material from the body.

Drug Interactions

With simultaneous use of atorvastatin with cyclosporine, HIV protease inhibitors (indinavir, ritonavir), antibiotics (Erythromycin, clarithromycin, quinupristin / dalfopristin), anti-fungal drugs from the group of azoles (fluconazole, itraconazole, ketoconazole), nefazodone, fibric acid derivatives, nicotinic acid in the plasma concentration of atorvastatin increases, which increases the risk of myopathy and rhabdomyolysis with acute renal failure.

While the use of erythromycin C_makh Atorvastatin is increased by 40%.

Simultaneous administration of atorvastatin with phenytoin may reduce the effectiveness of atorvastatin.

In a joint application antacids (slurry of magnesium hydroxide and aluminum) reduce the amount of atorvastatin in plasma.

At the same time taking atorvastatin with colestipol concentration of atorvastatin in plasma is reduced by 25%, but the therapeutic effect of the combination of the above, than the effect of one drug.

The simultaneous use of drugs, reduces the concentration of endogenous steroid hormones (incl. cimetidine, ketoconazole, spironolactone), It increases the risk of reducing the endogenous steroid hormones (Caution should be exercised).

Patients, simultaneously receiving atorvastatin 80 mg and digoxin, of digoxin in plasma increases by about 20%. Sick, receiving this combination, should be under the supervision of a physician.

In an application with oral contraceptives (combination norэtisterona and эtinilэstradiola) may increase the absorption of contraceptives and increasing their concentrations in blood plasma. It is therefore necessary to control the selection of contraceptives in women, receiving atorvastatin.

Simultaneous administration of atorvastatin and warfarin may intensify in the early days of warfarin on blood clotting parameters (decrease of prothrombin time). This effect disappears after 15 days of simultaneously receiving these drugs.

Simultaneous use of atorvastatin with protease inhibitors is accompanied by an increase in the plasma concentration of atorvastatin.

Clinically significant interactions were observed with cimetidine.

Drinking grapefruit juice in the treatment of Atoris^® may lead to increased concentrations of atorvastatin in plasma. Therefore patients, taking Atoris^®, You should avoid drinking this juice.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 2 year.