Composition, form of production and packaging
The tablets covered with a film cover of yellow color, round, biconcave; On the fracture, two layers are visible, the core is from white to almost white.
1 tab.
atorvastatin calcium 20.68 mg,
which corresponds to the content of atorvastatin 20 mg
Excipients: microcrystalline cellulose - 43.7 mg, lactose monohydrate - 54.95 mg, calcium carbonate - 5 mg, povidone - 5 mg, silicon dioxide colloid - 5 mg, carmellose sodium - 7 mg, magnesium stearate - 3 mg.
Composition of the film coat: hypromellose - 4.1 mg, macrogol 6000 - 1.2 mg, titanium dioxide - 0.6 mg, talc - 1.2 mg, iron oxide, yellow oxide - 0.07 mg.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
The tablets covered with a film cover of dark pink color, round, biconcave; On the fracture, two layers are visible, the core is from white to almost white.
1 tab.
atorvastatin calcium 10.34 mg,
which corresponds to the content of atorvastatin 10 mg
Excipients: cellulose microcrystalline - 54.4 mg, lactose monohydrate - 54.95 mg, calcium carbonate - 5 mg, povidone - 5 mg, silicon colloidal dioxide - 5 mg, croscarmellose sodium - 7 mg, magnesium stearate - 3 mg.
Composition of the film membrane: hypromellose - 4.1 mg, macrogol 6000 - 1.2 mg, titanium dioxide - 0.6 mg, talc - 1.2 mg, iron oxide, red oxide - 0.07 mg.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
PHARMACHOLOGIC EFFECT
A hypolipidemic agent from the group of statins. A selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonic acid, a precursor of sterols, including cholesterol. Triglycerides (TG) and cholesterol in the liver are included in the composition, very low density lipoproteins (VLDL), enter the blood plasma and transport to peripheral tissues. Low density lipoproteins (LDL) are formed from VLDL in the course of interaction with LDL receptors. Atorvastatin reduces the concentration of cholesterol and lipoproteins in the blood plasma, inhibiting HMG-CoA reductase, the synthesis of cholesterol in the liver, and the increase in the number of "hepatic" LDL receptors on the cell surface, which leads to increased capture and
catabolism of LDL. Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces the concentration of LDL in patients with homozygous familial hypercholesterolemia, which usually does not respond to lipid-lowering therapy. Reduces the concentration of total cholesterol by 30-46%, LDL by 41-61%, apolinoprotein B - by 34-50% and TG by 14-33%; causes an increase in the concentration of HDL cholesterol (high-density linoprotcins) and apolipoprotein A. Dozozavisimo reduces the level of LDL in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering drugs.
PHARMACOKINETICS
Absorption is high. With max in blood plasma is achieved in 1-2 hours, C max in women is higher by 20%, the area under the concentration-time curve (AUC) is lower by 10%; With max in patients with alcoholic cirrhosis of the liver 16 times, AUC- 11 times higher than normal.
Eating slightly reduces the speed and duration of absorption of the drug (by 25% and 9%, respectively), but the reduction in LDL cholesterol is similar to that of atorvastatin without food. The concentration of atorvastatin when used in the evening is lower than in the morning (about 30%). A linear relationship between the degree of absorption and the dose of the drug has been revealed.
Bioavailability - 12%, systemic bioavailability of inhibitory activity against HMG-CoA reductase - 30%. Low systemic bioavailability is due to presystemic metabolism in the mucosa of the gastrointestinal tract and "first pass" through the liver.
V d - 381 l, communication with blood plasma proteins - 98%. Metabolised mainly in the liver under the action of isoenzymes CYP3A4, CYP3A5 and CYP3A7 with the formation of pharmacologically active metabolites (ortho- and para-hydroxylated derivatives, beta-oxidation products). In vitro, ortho- and parahydroxylated metabolites exert an inhibitory effect on HMG-CoA reductase, comparable to that of atorvastatin. The inhibitory effect of the drug against HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites.
It is excreted through the intestine with bile after hepatic and / or extrahepatic metabolism (it does not undergo significant intestinal hepatic recirculation). T 1/2 - 14 h. The inhibitory activity against HMG-CoA reductase remains about 20-30 h due to the presence of active metabolites. Less than 2% of the dose taken internally is determined in the urine. It is not excreted during hemodialysis.
INDICATIONS
- combined with a diet to reduce elevated levels of total cholesterol, cholesterol / LDL, apolipoprotein B and triglycerides, and increase in HDL cholesterol in patients with primary hypercholesterolemia, heterozygous familial and non-family hypercholesterolemia, and combined hyperlipidemia (types IIa and IIb according to Fredrickson) ;
- in combination with a diet for the treatment of patients with elevated serum triglyceride levels (Fredrickson type IV) and patients with disbetalipoproteinemia (type III Fredrickson), in whom diet therapy does not provide an adequate effect;
- to reduce total cholesterol and cholesterol / LDL cholesterol in patients with homozygous familial hypercholesterolemia, when diet therapy and other non-pharmacological treatments are not effective enough.
DOSING MODE
Before the appointment of Vasator, the patient should recommend a standard lipid-lowering diet, which he must continue to observe during the entire period of therapy.
The initial dose is on average 10 mg 1 time / day. The dose varies from 10 to 80 mg once a day.
The drug can be taken at any time of the day with food or whatever time it takes to eat. The dose is selected taking into account the initial levels of cholesterol / LDL, the purpose of therapy and individual effect. At the beginning of treatment and / or during an increase in the dose of atorvastatin, it is necessary to monitor the plasma lipid concentrations every 2-4 weeks and adjust the dose accordingly.
Primary hypercholesterolemia and mixed hyperlipidemia. and also type III and IV according to Fredrickson: in most cases it is sufficient to prescribe a dose of 10 mg of the drug Vasator 1 time / day. A significant therapeutic effect is observed after 2 weeks, as a rule, and the maximum therapeutic effect is usually observed after 4 weeks. With prolonged treatment, this effect persists.
Homozygous familial hypercholesterolemia: the drug is used in a dose of 80 mg (4 tablets of 20 mg) 1 time / day. Do not use more than 4 tablets dosage of 10 mg per day - you can not replace the dose of 20 mg - 10 mg dose at a daily dose of 80 mg
The use of the drug in patients with renal insufficiency and kidney disease does not affect the level of atorvastatin in the blood plasma or the degree of decrease in the cholesterol / LDL value when it is used, therefore, a change in the dose of the drug is not required.
For hepatic insufficiency, the dose should be reduced (see the sections "With caution" and "Special instructions").
When using the drug in elderly patients, there were no differences in safety, efficacy, or achievement of lipid-lowering therapy goals in comparison with the general population.
SIDE EFFECT
From the side of the central nervous system: insomnia, dizziness, headache, asthenia, malaise, drowsiness, nightmarish dreams, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesia, migraine, depression, hypoesthesia, loss of consciousness.
From the sense organs: amblyopia, ringing in the ears, dryness of the conjunctiva, disruption of accommodation, bleeding in the retina, deafness, glaucoma, parosmia, loss of taste sensations, taste distortion.
From the cardiovascular system: chest pain, palpitation, symptoms of vasodilation, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina.
On the part of the hematopoiesis system: anemia, lymphadenopathy, thrombocytopenia.
On the part of the respiratory system : bronchitis, rhinitis, pneumonia, dyspnoea, exacerbation of bronchial asthma, nosebleeds.
On the part of the digestive system: nausea, heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive ulcerative lesions of the oral mucosa , gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, liver dysfunction, rectal bleeding, melena, bleeding gums, tenesmus.
From the musculoskeletal system: arthritis; leg muscle cramps, bursitis, tendosinovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscular hypertonia, joint contractures.
From the genitourinary system: urogenital infections, peripheral edema; dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, mandatory urges to urinate), nephritis, hematuria, vaginal bleeding, nephrourolythiasis, metrorrhagia, epididymitis, decreased libido, impotence, ejaculatory impairment.
From the skin: alopecia, xeroderma, increased sweating, eczema, seborrhea, ecchymosis, petechiae.
Allergic reactions: skin itching, skin rash, contact dermatitis, urticaria, aygoneurotic edema, facial edema, photosensitivity, anaphylaxis, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).
Laboratory indicators: hyperglycemia, hypoglycemia, increased serum creatine phosphokinase (CK), albuminuria.
Other: weight gain, gynecomastia, mastodynia, exacerbation of gout.
CONTRAINDICATIONS
- hypersensitivity to the components of the drug;
- active liver disease or increased activity of "hepatic" enzymes of unknown origin (more than 3 times compared with the upper limit of the norm); hepatic failure (grade A and B severity according to Child-Pugh classification);
- Pregnancy;
- lactation period;
- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
- age under 18 years (efficiency and safety not established).
With caution: alcohol abuse, liver disease in history, severe water-electrolyte balance disorders, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, injuries, skeletal muscle diseases.
PREGNANCY AND LACTATION
The Vasatorum is contraindicated for use in pregnancy and lactation (breastfeeding).
It is not known whether atorvastatin is excreted in breast milk. Given the possibility of developing adverse events in infants, if the drug is needed during lactation, the question of stopping breastfeeding should be addressed.
Women of reproductive age during treatment should use adequate methods of contraception.
The vaccinator can be prescribed to women of reproductive age only if the probability of pregnancy is very low, and the patient is informed of the possible risk of treatment for the fetus.
APPLICATION FOR FUNCTIONS OF THE LIVER
The use of the drug in patients with renal insufficiency and kidney disease does not affect the level of atorvastatin in the blood plasma or the degree of decrease in the cholesterol / LDL value when it is used, therefore, a change in the dose of the drug is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated with active liver disease or increased activity of "liver" enzymes of unknown origin (more than 3 times compared with the upper limit of the norm);with hepatic insufficiency (degree of severity in classes A and B according to the Child-Pugh classification).
With caution: liver disease in the anamnesis.
APPLICATION FOR CHILDREN
Contraindicated at the age of 18 years (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
When using the drug in elderly patients, there were no differences in safety, efficacy, or achievement of lipid-lowering therapy goals in comparison with the general population.
SPECIAL INSTRUCTIONS
Before starting therapy with Vasator, the patient should be prescribed a standard hypocholesterolemic diet, which he must observe during the entire treatment period.
The use of HMG-CoA reductase inhibitors to reduce lipid levels in the blood can lead to a change in biochemical parameters that reflect the function of the liver. The liver function should be monitored before the start of therapy, 6 weeks, 12 weeks after the commencement of taking the Vasator and after each dose increase, and periodically, for example, every 6 months. An increase in the activity of "hepatic" enzymes in the blood serum can be observed during therapy with Vasator. Patients who have an increase in enzyme activity should be monitored before the enzyme activity returns to normal. In the event that ALT or ACT values ​​are more than 3 times higher than the upper limit, it is recommended to reduce the dose of Vasator or stop treatment.
The Vasator should be used with caution in patients who abuse alcohol and / or have liver disease. Active liver disease or persistent increase in the activity of "hepatic" transferases of unknown origin serve as contraindications to the appointment of Vasator.
Treatment with a Vasator may cause myopathy. The diagnosis of myopathy (pain and weakness in muscles, combined with an increase in CKK activity by more than 10 times compared with the upper limit of normal) should be discussed in patients with common myalgia, tenderness or weakness of the muscles and / or a marked increase in CKK activity. Patients should be warned that they should immediately inform the doctor of unexplained pain or weakness in the muscles if they are accompanied by a malaise or fever. Therapy should be discontinued in the case of a marked increase in the activity of CK or in the presence of confirmed or suspected myopathy. The risk of myopathy in treatment with other drugs of this class increased with simultaneous use of cyclosporine, fibrates, erythromycin, nicotinic acid in lipid-lowering doses or azole antifungal agents. Many of these drugs inhibit the metabolism mediated by the CYPZA4 isoenzyme and / or drug transport. Atorvastatin is biotransformed by the action of the CYPZA4 isoenzyme. Assigning the Vasator in combination with fibrates, erythromycin, immunosuppressive agents, azole antifungal agents or nicotinic acid in lipid lowering doses should carefully weigh the expected benefit and risk of treatment and monitor patients regularly to identify pain or weakness in the muscles, especially during the first months of treatment and in the period of increasing the dose of any drug. In such situations, it is possible to recommend a periodic determination of the activity of CKK, although such control does not prevent the development of severe myopathy.
When using Vasator, as well as other drugs of this class, cases of rhabdomyolysis with acute renal failure due to myoglobinuria are described. The drug should be temporarily discontinued or completely discontinued if there is evidence of possible myopathy or the presence of a risk factor for developing renal failure against rhabdomyolysis (eg, severe acute infection, arterial hypotension, extensive surgery, trauma, severe metabolic, endocrine and electrolyte disturbances and uncontrolled seizures ).
Before starting therapy with Vasator, it is necessary to try to achieve control of hypercholesterolemia by adequate diet therapy, increasing physical activity, reducing body weight in obese patients and treating other conditions. Patients should be warned that they should immediately consult a doctor if unexplained pain or weakness in the muscles occurs, especially if they are accompanied by a malaise or fever.
Impact on the ability to drive vehicles and manage mechanisms
In some patients, the drug may cause dizziness and other side effects that may affect the ability to drive vehicles and work with mechanisms. In this regard, when treating Vasator, care should be taken when managing vehicles and other complex mechanisms that require increased attention.
OVERDOSE
Treatment: there is no specific antidote, symptomatic therapy is performed. Hemodialysis is ineffective.
DRUG INTERACTION
The risk of myopathy during treatment with other drugs of this class is increased by the simultaneous use of cyclosporine, fibrates, erythromycin, antifungal agents related to azoles and nicotinic acid. At simultaneous ingestion of atorvastatin and a suspension containing magnesium and aluminum hydroxide, the concentrations of atorvastatin in plasma decreased blood by about 35%, but the degree of decrease in the level of cholesterol / LDL did not change. With simultaneous use of atorvastatin does not affect the pharmacokinetics of the antipyrine (phenazone), so interaction with other agents metabolized by the same isoenzymes of cytochrome is not expected.
With simultaneous application kolestipolakontsentratsii atorvastatin plasma decreased by about 25%. However hypolipidemic effect of the combination of atorvastatin and colestipol than that of each drug separately. Repeated dose digoksinai atorvastatin 10 mg of the equilibrium concentration of digoxin in plasma did not change. However, the application of digoxin in combination with atorvastatin 80 mg / day digoxin concentrations increased by approximately 20%. Patients receiving digoxin in combination with atorvastatin, should be observed. With simultaneous application of atorvastatin and erythromycin (500 mg four times / day) or clarithromycin (500 mg, 2 times / day), which inhibits isozyme CYPZA4 observed increase atorvastatin plasma concentration.With simultaneous use of atorvastatin (10 mg 1 time / day) and azithromycin (500 mg 1 time / day) atorvastatin plasma concentration was not changed.
Atorvastatin had no clinically significant effect on the concentration terfenadinav blood plasma, which is metabolized mainly CYPZA4; therefore it seems unlikely that atorvastatin can significantly affect the pharmacokinetic parameters of other substrates CYPZA4 isoenzyme.
With simultaneous use of atorvastatin and oral contraceptive containing ethinylestradiol and norethisterone, there was a significant increase in AUC of norethindrone and ethinyl estradiol is about 30% and 20% respectively. This effect should be considered when selecting an oral contraceptive for a woman receiving atorvastatin.
The simultaneous use of drugs, which reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone), increases the risk of reduction of endogenous steroid goromonov (caution).
When studying the interaction with warfarin and atorvastatin tsimetidinompriznakov clinically significant interactions were detected.
With simultaneous use of atorvastatin 80 mg or amlodipine 10 mg atorvastatin pharmacokinetics in the equilibrium state is not changed.
There were no clinically significant adverse interactions atorvastatin and antihypertensives funds.
Simultaneous use of atorvastatin with protease inhibitors, known as the isoenzyme inhibitors CYPZA4, accompanied by an increase atorvastatin plasma concentration. Pharmaceutical incompatibility is unknown.
TERMS OF RELEASE FROM PHARMACY
On prescription.
TERMS AND CONDITIONS OF STORAGE
Keep out of reach of children, dry and dark place at a temperature not higher than 25 В° C.
Shelf life - 2 years.
