Atorvastatin Ananta 20 mg tablets # 30

Author Ольга Кияница

2017-05-11

Amount in a package 30
Product form Pills
Manufacturer Ananta Medicare (UK)
Registration certificate UA/0689/01/01
The main medicament Atorvastatin
morion code 275451

Atorvastatin (ATORVASTATIN) instructions for use

Composition

active ingredient: atorvastatin; 1 tablet contains atorvastatin calcium in terms of atorvastatin 10 mg or 20 mg;
auxiliary substances: lactose monohydrate, microcrystalline magnesium cellulose sodium stearate croscarmellose;starch corn hydroxypropylcellulose; hydroxypropylmethylcellulose; polyethylene glycol; titanium dioxide (E 171).

Dosage form

Film-coated tablets.

Basic physical and chemical properties:

white or almost white round biconvex tablets, covered with a film sheath.

Pharmacological group

Lipid-lowering drugs, multicomponent. HMG CoA reductase inhibitors. ATX Code C10A A05.

Pharmacological properties

Pharmacodynamics.

A selective competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A-reductase enzyme converting 3-hydroxy-3-methylglutaryl coenzyme A into mevalonic acid, which is a precursor of sterols, including cholesterol. Atorvastatin reduces cholesterol and lipoprotein levels in blood plasma by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol synthesis in the liver, as well as an increase in the number of LDL receptors on the surface of hepatocytes, which leads to increased capture and catabolism of LDL. Atorvastatin reduces the level of total cholesterol, low-density lipoproteins, apolipoprotein B and triglycerides, which causes an increase in high-density lipoprotein cholesterol and apolipoprotein A. These results are recorded in patients with heterozygous familial hypercholesterolemia and mixed hyperlipidemia, including patients with insulin-dependent diabetes mellitus.

Pharmacokinetics.

Atorvastatin is rapidly absorbed after administration; the maximum concentration in blood plasma is achieved in 1-2 hours. The degree of absorption increases in proportion to the dose of atorvastatin. Bioavailability is 95-99%. The bioavailability of atorvastatin is approximately 14%, and the systemic availability of inhibitory activity against 3-hydroxy-3-methylglutaryl coenzyme A-reductase is about 30%. Low systemic bioavailability is due to presystemic clearance in the mucous membrane of the gastrointestinal tract and / or biotransformation during primary passage through the liver.The average volume of atorvastatin distribution is approximately 381 liters. Atorvastatin binds to blood plasma proteins by more than 98%, is metabolized by cytochrome P450 3 A4 with the formation of ortho and parahydroxylation derivatives and various β-oxidation products. The effect of atorvastatin on 3-hydroxy-3-methylglutarylcoenzyme reductase is approximately 70% determined by the activity of circulating metabolites. It is excreted with bile after hepatic and / or extrahepatic biotransformation. The drug is not subject to severe intestinal hepatic recirculation. The half-life of atorvastatin is almost 14 hours. The inhibitory activity against 3-hydroxy-3-methylglutarylcoenzyme A-reductase lasts about 20-30 hours due to the presence of active metabolites. The pharmacokinetics of the drug in children are absent.

Table 1. Effect of concurrently used drugs on the pharmacokinetics of atorvastatin.

Simultaneously used drugs and dosing regimen
Atorvastatin
Dose (mg)
The change in AUC &
Changing Cmax &
# Cyclosporine 5.2 mg / kg / day, stable dose
10 mg once daily for 28 days
8.7 times
10.7 times
# Tipranavir 500 mg twice daily / ritonavir 200 mg twice daily, 7 days
10 mg of RD
9.4 times
8.6 times
# Telaprevir 750 mg every 8:00, 10 days
20 mg of RD
7,88 times
10.6 times
#, ‡ Saquinavir 400 mg twice daily / ritonavir 400 mg twice daily, 15 days
40 mg once daily for 4 days
3.9 times
4.3 times
# Clarithromycin 500 mg twice daily, 9 days
80 mg once a day for 8 days
4.4 times
5,4 times
# Darunavir 300 mg twice daily / ritonavir 100 mg twice daily, 9 days
10 mg once a day for 4 days
3,4 times
2.25 times
# Itraconazole 200 mg 1 rd, 4 days
40 mg of RD
3.3 times
20%
# Fosamprenavir 700 mg twice daily / ritonavir 100 mg twice daily, 14 days
10 mg once daily for 4 days
2.53 times
2.84 times
# Fosamprenavir 1400 mg 2 times a day, 14 days
10 mg once a day for 4 days
2.3 times
4.04 times
# Nelfinavir 1250 mg 2 times a day, 14 days
10 mg once a day for 28 days
74%
2.2 times
# Grapefruit juice, 240 ml once a day *
40 mg once a day
37%
16%
Diltiazem 240 mg once a day, 28 days
40 mg once a day
51%
without change
Erythromycin 500 mg 4 times a day, 7 days
10 mg once a day
33%
38%
Amlodipine 10 mg, single dose
80 mg once daily
15%
12%
Cimetidine 300 mg once a day, 4 weeks
10 mg once a day for 2 weeks
¯ Less than 1%
eleven%
Colestipol 10 mg twice daily, 28 weeks
40 mg once a day for 28 weeks
indefined
¯ 26% **
Maalox TC ® 30 ml once daily, 17 days
10 mg once a day for 15 days
¯ 33%
¯ 34%
Efavirenz 600 mg once a day, 14 days
10 mg for 3 days
¯ 41%
1%
# Rifampin 600 mg once daily, 7 days (with simultaneous administration) †
40 mg once a day
thirty%
2.7 times
# Rifampin 600 mg once daily, 5 days (in separate doses) †
40 mg once a day
¯ 80%
¯ 40%
# Gemfibrozil 600 mg twice daily, 7 days
40 mg once a day
35%
¯ Less than 1%
# Fenofibrate 160 mg once a day, 7 days
40 mg once a day
3%
2%
# Boceprivir 800 mg 3 times a day, 7 days
40 mg once a day
2.30 times
2.66 times

& Data presented as a change x times is a simple relationship between cases of simultaneous use of drugs and the use of only atorvastatin (i.e., 1-fold = unchanged). The data presented in the% change is the% difference in the indices of atorvastatin alone (i.e., 0% = unchanged).

# For information on clinical significance, see the sections on "Features of Use" and "Interaction with Other Drugs and Other Interactions".

* A large increase in AUC (up to 2.5 times) and / or C max (up to 71%) was reported with excessive consumption of grapefruit juice (750 ml - 1.2 liters per day or more).

** A single sample taken 8-16 hours after taking the drug.

† The simultaneous use of atorvastatin with rifampin is recommended through the mechanism of double interaction of rifampin, as it was shown that the delayed use of atorvastatin after rifampin is associated with a significant decrease in concentrations of atorvastatin in plasma.

‡ The dose of saquinavir + ritonavir combination in this study is not a clinically applicable dose. Increasing the exposure of atorvastatin when used in clinical settings is likely to be higher than that observed in this study. Therefore, it is necessary to use the drug with caution in a low required dose.

Indications

Prevention of cardiovascular disease

For adults without clinically severe coronary heart disease, but with several risk factors for developing coronary heart disease such as age, smoking, hypertension, low HDL cholesterol, or the presence of an early ischemic heart disease in a family history, Atorvastatin Ananta is indicated for:

  • reduction in the risk of myocardial infarction
  • reducing the risk of stroke;
  • reducing the risk of revascularization procedures and angina pectoris.

For patients with type 2 diabetes mellitus and without clinically severe ischemic heart disease, but with several risk factors for coronary heart disease such as retinopathy, albuminuria, smoking or hypertension, the drug Atorvastatin Ananta is indicated for:

  • reduction in the risk of myocardial infarction
  • reduction of the risk of stroke.

For patients with clinically severe ischemic heart disease, Atorvastatin Ananta is indicated for:

  • decrease in the risk of non-lethal myocardial infarction
  • reduction in the risk of lethal and non-lethal stroke;
  • reducing the risk of revascularization procedures;
  • reduction in the risk of hospitalization due to congestive heart failure,
  • reduction in the risk of angina pectoris.

Hyperlipidemia

In addition to diet to reduce elevated levels of total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides, and also to increase HDL cholesterol in patients with primary hypercholesterolemia (heterozygous familial and non-family) and mixed dyslipidemia (type IIa and IIb according to Fredrickson classification) .
As a supplement to the diet for the treatment of patients with elevated serum triglyceride levels (Fredrickson type IV).
For the treatment of patients with primary dysbetalipoproteinemia (type III according to Fredrikson's classification), in cases when diet compliance is not effective enough.
To reduce total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL-apheresis), or if such treatments are not available.
As a supplement to the diet to reduce the levels of total cholesterol, LDL cholesterol and apolipoprotein B in boys and girls after the onset of menstruation at the age of 10 to 17 years with heterozygous familial hypercholesterolemia, if after appropriate diet therapy the results of the tests are:
a) LDL cholesterol remains ³ 190 mg / dl or

b) LDL cholesterol ≥ 160 mg / dl and:

in a family history there are early cardiovascular diseases or
Two or more other risk factors for the development of cardiovascular disease are present in a pediatric patient.

Contraindications

Active liver disease, which can include a steady increase in the activity of hepatic transaminases of unclear etiology.

Hypersensitivity to any of the components of this drug.

Interaction with other drugs and other interactions

The risk of developing myopathy during statin treatment is increased when concurrent use is made of fibrolic acid derivatives, lipidomodification doses of niacin, cyclosporine, or potent inhibitors of CYP 3A4 (eg clarithromycin, HIV protease inhibitors and itraconazole) (see Sections "Application Specificities").

Powerful inhibitors of CYP 3A4. Atorvastatin is metabolized by cytochrome P450 3A4. The simultaneous use of atorvastatin with potent inhibitors of CYP 3A4 can lead to an increase in the concentration of atorvastatin in blood plasma (see Table 1 and detailed information below). The degree of interaction and enhancement of action depends on the variability of the effect on CYP 3A4. If possible, simultaneous use with potent inhibitors of CYP3A4 should be avoided (for example, with cyclosporine, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors, including ritonavir, lopinavir, atazanavir, indinavir, darunavir). If simultaneous use of these drugs with atorvastatin can not be avoided, consideration should be given to the use of lower initial and maximum doses of atorvastatin. It is also recommended that proper clinical monitoring of the patient's condition be performed (see Table 1).

Moderate inhibitors of CYP3A4 (eg erythromycin, diltiazem, verapamil and fluconazole) can increase the concentration of atorvastatin in the blood plasma (see Table 1). Simultaneous use of erythromycin and statins is accompanied by an increased risk of myopathy. The study of the interaction of drugs to assess the effect of amiodarone or verapamil on atorvastatin was not conducted. It is known that amiodarone and verapamil suppress the activity of CYP3A4, and consequently, the simultaneous administration of these drugs with atorvastatin may lead to an increase in exposure to atorvastatin. Thus, with the simultaneous use of atorvastatin and these moderate inhibitors of CYP3A4, consideration should be given to the possibility of assigning smaller maximum doses of atorvastatin. Clinical monitoring of the patient's condition is also recommended. After the initiation of treatment with an inhibitor or after correcting its dose, it is recommended that the clinical monitoring of the patient's condition is recommended.

Grapefruit juice. Contains one or more components that inhibit CYP 3A4 and can increase the concentration of atorvastatin in the blood plasma, especially with excessive consumption of grapefruit juice (more than 1.2 liters per day).

Clarithromycin. The value of AUC of atorvastatin was significantly increased with simultaneous use of atorvastatin 80 mg and clarithromycin (500 mg twice daily) compared with the use of atorvastatin alone. Thus, in patients taking clarithromycin, caution should be used atorvastatin Ananta at a dose of 20 mg (see Sections "Features of application" and "Method of administration and dose").

Combination of protease inhibitors. The value of AUC of atorvastatin increased significantly with the simultaneous use of atorvastatin with several combinations of HIV protease inhibitors, as well as with the protease inhibitor of hepatitis C virus, telaprevir, compared with the use of atorvastatin alone. Therefore, patients taking the HIV protease inhibitor tipranavir + ritonavir or hepatitis C protease inhibitor telaprevir should avoid concomitant use with the drug Atorvastatin Ananta. The drug should be administered with caution to patients who take the HIV protease inhibitor lopinavir + ritonavir and apply it in the most appropriate dose. For patients taking saquinavir + ritonavir, darunavir + ritonavir, fosamprenavir, or fosamprenavir + ritonavir, protease inhibitors, the dose of atorvastatin Anant should not exceed 20 mg and should be used with caution (see Sections "Features of Use" and "Dosage and Administration"). When using nelfinavir or a protease inhibitor of hepatitis C virus bocheprevir in patients taking a protease inhibitor of HIV, the dose of atorvastatin Anant should not exceed 40 mg, and careful clinical monitoring of patients is recommended.

Itraconazole. The value of AUC of atorvastatin was significantly increased with simultaneous use of atorvastatin 40 mg and itraconazole at a dose of 200 mg. Thus, patients taking itraconazole should be cautious if the dose of atorvastatin Anant exceeds 20 mg (see Sections "Features of application" and "Method of administration and dose").

Cyclosporine. Atorvastatin and its metabolites are the substrates of the OATP1B1 transporter. Inhibitors of OATP1B1 (eg, cyclosporin) may increase the bioavailability of atorvastatin. The value of AUC of atorvastatin was significantly increased with simultaneous use of atorvastatin 10 mg and cyclosporine at a dose of 5.2 mg / kg / day compared with the use of atorvastatin alone. Avoid simultaneous use of atorvastatin Anant and cyclosporine (see section "Features of application").

Medical recommendations for the use of medicaments interacting are summarized in Table 2 (see also the sections "Method of administration and dose", "Application features").

Table 2.

Interactions of drugs associated with an increased risk of myopathy / rhabdomyolysis.

Preparations interact
Medical recommendations for use
Cyclosporine, HIV protease inhibitors (tipranavir + ritonavir), hepatitis C virus protease inhibitor (telaprevir)
Avoid the use of atorvastatin
The HIV protease inhibitor (lopinavir + ritonavir)
Use with caution and in lesser dosage
Clarithromycin, itraconazole,
HIV protease inhibitors (saquinavir + ritonavir * darunavir + ritonavir, fosamprenavir, fosamprenavir + ritonavir)
Exceed the dose of 20 mg of atorvastatin per day
HIV protease inhibitor (nelfinavir)
The protease inhibitor of the hepatitis C virus (bocetrevir)
Exceed the dose of 40 mg of atorvastatin per day

Use with caution and in a smaller appropriate dose.

Gemfibrozil. Due to the increased risk of myopathy / rhabdomyolysis with concomitant use of HMG-CoA reductase inhibitors with gemfibrozil, joint use of atorvastatin Anant with gemfibrozil should be avoided (see "Features of Use" section).

Other fibrates. Since it is known that the risk of developing myopathy during treatment with HMG-CoA reductase inhibitors increases with simultaneous administration of other fibrates, Atorvastatin Anant should be used with caution when used in conjunction with other fibrates (see section on "Features of Use").

Niacin. The risk of side effects from skeletal muscle may increase when used in combination with niacin, and therefore, under such conditions, the possibility of reducing the dose of atorvastatin Anant should be considered (see Section "Application Features").

Rifampicin or other inducers of cytochrome P450 3A4. Simultaneous use of the drug with cytochrome P450 3A4 inducers (eg efavirenz, rifampicin) can lead to an unstable decrease in the concentration of atorvastatin in the blood plasma. Through the mechanism of interaction of rifampin dual simultaneous application atorvastatin rifampin, since it has been shown that delayed administration of the preparation after administration of rifampin is associated with a significant reduction of atorvastatin concentrations in plasma.

diltiazem hydrochloride

Simultaneous treatment with atorvastatin (40 mg), and diltiazem (240 mg) was accompanied by increased concentrations of atorvastatin in the blood plasma.

cimetidine

As a result of evidence of studies of the interaction of cimetidine and atorvastatin was not revealed.

antacids

Simultaneous atorvastatin and oral antacid formulation a suspension containing magnesium and aluminum hydroxide, accompanied by a decrease in blood plasma concentration of atorvastatin for 35%. In this case, lipid-lowering effect of atorvastatin unchanged.

colestipol

plasma concentration of atorvastatin lower (approximately 25%), while taking atorvastatin and colestipol. Thus hypolipidemic effect of the combination of atorvastatin and colestipol exceed effect, which allows the reception of each of the drugs individually.

azithromycin

Simultaneous administration of atorvastatin (10 mg 1 time per day) and azithromycin (500 mg 1 time per day) was not accompanied by changes in the concentration of atorvastatin in plasma.

Inhibitors of transport proteins

Inhibitors of transport proteins (e.g. cyclosporin) can increase the systemic exposure level of atorvastatin (see. Table 1). The effect of suppressing accumulation of transport proteins on the concentration of atorvastatin in liver cells is unknown. If avoid simultaneous administration of these preparations impossible recommended dose reduction and clinical monitoring of the effectiveness of atorvastatin (see. Table 1).

ezetimibe

The use of ezetimibe as a monotherapy has been associated with effects from the musculoskeletal system, including rhabdomyolysis. Thus, while the use of ezetimibe and atorvastatin risk of these events is increased. It is recommended to carry out appropriate clinical monitoring of these patients.

fusidic acid

interaction and atorvastatin acid fuzidovoi study were not conducted. As is the case with other statins, a post-marketing period while taking atorvastatin and fuzidovoi acid phenomena observed by the muscular system (including rhabdomyolysis). The mechanism of this interaction is unknown. Patients need to be carefully monitored, may require the temporary suspension of treatment with atorvastatin.

Digoxin.With simultaneous use of multiple doses of atorvastatin and digoxin Digoxin equilibrium plasma concentrations increased by approximately 20%. It is necessary to properly monitor the status of patients taking digoxin.

Oral contraceptives.Simultaneous use of atorvastatin with oral contraceptives increased the AUC value for ethinylestradiol and norethisterone. These increases should be considered when selecting an oral contraceptive for women who take atorvastatin.

Warfarin. Atorvastatin had no clinically significant effect on the prothrombin time in the application of patients who were treated with warfarin for a long period.

Colchicine. With simultaneous use of atorvastatin with colchicine reported cases of myopathy, including rhabdomyolysis, should therefore be used with caution atorvastatin with colchicine.

Other drugs

Clinical studies have shown that the concurrent use of atorvastatin and antihypertensive drugs and their use in the course of estrogen replacement therapy was not associated with clinically significant side effects. Interaction studies with other drugs have not been conducted.

Features of the application

skeletal muscles

There are rare cases of rhabdomyolysis with acute renal failure due to the application myoglobinuria atorvastatin and other drugs in this class. A history of renal dysfunction may be a risk factor for the development of rhabdomyolysis. Such patients need closer monitoring to detect violations of the skeletal muscles.

Atorvastatin, like other drugs of the statin group sometimes cause myopathy, defined as muscle pain or weakness of muscles in conjunction with an increase in CPK indicators (CK) more than 10 times the upper limit of normal. The simultaneous use of high doses of atorvastatin with certain drugs such as cyclosporin and potent inhibitors of CYP3A4 (e.g. clarithromycin, itraconazole and HIV protease inhibitors) increases the risk of myopathy / rhabdomyolysis.

Use of a preparation of atorvastatin may cause immunologically mediated necrotising myopathy (IONM) - autoimmune myopathy associated with the use of statins. IONM is characterized by the following features: proximal muscle weakness and elevated levels of creatine kinase in the blood serum, which persist despite discontinuation of statin therapy; Muscle biopsy shows necrotizing myopathy without significant inflammation; the application of immunosuppressive agents observed a positive trend.

The possibility of developing myopathy should be considered in any patient with diffuse myalgia, muscle tenderness or weakness, and / or a significant increase in CPK. Patients should be advised to immediately report cases of muscle pain, tenderness, or weakness of the muscles of unknown etiology, particularly if it is accompanied by a feeling of malaise or fever, or if signs and symptoms of muscle disease persist after discontinuation of atorvastatin. Treatment should be discontinued in case of increase of CPK, diagnosis or suspicion of myopathy.

The risk of myopathy during treatment with this class of drugs is increased while the use of cyclosporine, fibric acid derivatives, erythromycin, clarithromycin, protease inhibitors of hepatitis C virus telaprevir, combinations of HIV protease inhibitors, including saquinavir + ritonavir, lopinavir + ritonavir, tipranavir + ritonavir, darunavir + ritonavir, fosamprenavir, and fosamprenavir + ritonavir, and niacin or antimycotic azole group. Doctors who are considering combination therapy atorvastatin and fibric acid derivatives, erythromycin, clarithromycin, combinations saquinavir + ritonavir, lopinavir + ritonavir, darunavir + ritonavir, fosamprenavir, fosamprenavir + ritonavir, antimycotics group azoles or lipidomodifitsiruyuschey doses of niacin should carefully weigh the potential benefits and risksand carefully monitor the condition of patients for any signs or symptoms of pain, tenderness, or weakness in the muscles, especially in the initial months of therapy and during any periods of dose titration in the direction of increase of any of the drugs. Should consider the use of low initial and maintenance doses of atorvastatin while taking the above drugs (see. Section "interaction with other drugs and other types of interactions"). In such situations, it may be considered for periodic determination of CK, but there is no assurance that such monitoring will prevent cases of severe myopathy.especially in the initial months of therapy and during any periods of dose titration in the direction of increasing any of the drugs. Should consider the use of low initial and maintenance doses of atorvastatin while taking the above drugs (see. Section "interaction with other drugs and other types of interactions"). In such situations, it may be considered for periodic determination of CK, but there is no assurance that such monitoring will prevent cases of severe myopathy.especially in the initial months of therapy and during any periods of dose titration in the direction of increasing any of the drugs. Should consider the use of low initial and maintenance doses of atorvastatin while taking the above drugs (see. Section "interaction with other drugs and other types of interactions"). In such situations, it may be considered for periodic determination of CK, but there is no assurance that such monitoring will prevent cases of severe myopathy.CATEGORY "Interaction with other drugs and other types of interactions"). In such situations, it may be considered for periodic determination of CK, but there is no assurance that such monitoring will prevent cases of severe myopathy.CATEGORY "Interaction with other drugs and other types of interactions"). In such situations, it may be considered for periodic determination of CK, but there is no assurance that such monitoring will prevent cases of severe myopathy.

When treating atorvastatin were observed occasionally cases of myopathy, including rhabdomyolysis, while the application of atorvastatin with colchicine, colchicine with atorvastatin therefore be administered with caution to patients (see. Section "interaction with other drugs and other types of interactions").

Atorvastatin Ananta should suspend or stop in any patient with an acute serious condition, indicates the development of myopathy, or if you have risk factors for renal failure due to rhabdomyolysis (eg severe acute infection, hypotension, surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).

Abnormal liver function

It has been shown that statins as hypolipidemic and some other therapeutic agents associated with abnormal biochemical indicators of liver function. Persistent increase (more than 3 times the upper limit of the normal range, which occurred 2 times or more) levels of serum transaminases observed in 0.7% of patients receiving atorvastatin. The incidence of this abnormality was 0.2%, 0.2%, 0.6% and 2.3% for doses of 10, 20, 40 and 80 mg, respectively.

There is evidence that while taking the drug in one patient developed jaundice. Improving the performance of liver function tests (FPP) in the other patients were not associated with jaundice or other clinical signs and symptoms. After dose reduction interruption or termination of application of the preparation of application transaminase levels returned to the levels before treatment or about these levels without sequelae. 18 of 30 patients with a stable increase in liver function tests indicators continued treatment with atorvastatin in smaller doses.

Before starting therapy with atorvastatin Ananta, it is recommended to get the results of analyzes of the liver enzymes to be tested again in the case of clinical need. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking drugs of statins, including atorvastatin. In case of severe liver disease with clinical symptoms and / or hyperbilirubinaemia or jaundice should be stopped immediately when applying atorvastatin. If an alternate etiology is not defined, do not re-start the treatment with the drug.

Atorvastatin Anantha be used with caution in patients taking significant amounts of alcohol and / or have a history of liver disease. Atorvastatin is contraindicated in liver Anantha active disease or persistent elevations in liver transaminases of unknown etiology (see. Section: "Contra ').

endocrine function

It reported an increased level of HbA1c concentration and serum fasting glucose when using the HMG-CoA reductase inhibitors, including atorvastatin.

Statins inhibit cholesterol synthesis and theoretically may reduce the secretion of adrenal and / or gonadal steroids. Clinical studies have shown that atorvastatin does not reduce basal plasma cortisol concentration and does not damage the adrenal reserve. The effect of statins on sperm fertilizing ability have not investigated in a sufficient number of patients. It is not known how the drug affects, and generally affects the system "sex glands-pituitary-hypothalamus" in women in the premenopausal period. Caution must be exercised while the use of the drug with the statin drugs, which may reduce the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone and cimetidine.

The use in patients with recent cases of stroke or transient ischemic attack

When therapy with atorvastatin 80 mg in patients without coronary artery disease who had a history of stroke or transient ischemic attack within the previous 6 months, there was a large incidence of hemorrhagic stroke.

Among patients treated with atorvastatin at the age of 65-75 years, there was no no general differences in safety and efficacy between these patients and younger patients, as well as had been recorded no differences in response to treatment in elderly patients and younger patients but we can not exclude a greater sensitivity of some older patients. Since older age (65 years) is a factor of predisposition to myopathy, should be used with caution Atorvastatin Ananta elderly.

Liver failure

Ananta Atorvastatin is contraindicated in patients with active liver disease, including persistent elevation of liver transaminases of unknown etiology (see. Sections "Contraindications").

Prior to treatment

Atorvastatin should be used with caution in patients with a propensity for the development of rhabdomyolysis. Prior to initiating treatment with statins in patients who are prone to the development of rhabdomyolysis, should determine the level of the Criminal Code when:

  • impaired renal function
  • hypothyroidism;
  • hereditary muscular system disorders in a family history or personal
  • endured in the past cases, the toxic effects of statins or fibrates in the muscles;
  • endured in the past liver disease and / or use of large amounts of alcohol.

For elderly patients (70 years), the need for these measures should be evaluated taking into account the presence of other factors predisposing to the development of rhabdomyolysis.

Increasing the plasma level of the drug may, in particular, in the case of interaction and the application of special populations of patients, including patients with hereditary diseases.

In such cases it is advisable to evaluate the ratio of risk and potential benefit from the treatment and to conduct clinical monitoring of patients. If CC before treatment level significantly increased (BMH exceeds more than 5 times), the treatment should not begin.

Measurement of CK

CPK levels should not be determined after intense exercise or in the presence of any possible alternative causes of increased levels of the Criminal Code, as it may complicate the interpretation of the results. If a significant increase in the Criminal Code (exceeding the upper limit of normal in more than 5 times) was observed at the initial level, then after 5-7 days it is necessary to re-determination to confirm the result.

During treatment

Patients should be aware of the need to immediately report on the development of muscle pain, court or weakness, particularly if accompanied by malaise or fever.

In case of these symptoms during treatment with atorvastatin is necessary to determine the level of QC in this patient. If CC level is significantly elevated (BMH exceeds more than 5 times), treatment should cease.

The expediency of treatment discontinuation should also be considered, if the rise of the Criminal Code does not reach the level of fivefold excess capital punishment, but by muscle symptoms are severe in nature and every day can become a cause of discomfort.

After the disappearance of symptoms and normalization CC level can consider resuming atorvastatin or alternative start of treatment with statins provided use the lowest possible dose and careful monitoring of the patient.

Treatment with atorvastatin should be discontinued if there is a clinically significant increase in the level of the Criminal Code (exceeding the upper limit of normal in more than 10 times) or in the case of diagnosis of rhabdomyolysis (or suspected rhabdomyolysis).

The simultaneous use of other drugs

The risk of rhabdomyolysis is increased while the application of atorvastatin with certain drugs which can increase the concentration of atorvastatin in plasma. Examples of such drugs can act potent inhibitors of CYP3A4 or transport proteins cyclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir. While the use of gemfibrozil and other fibric acid derivatives, erythromycin, niacin and ezetimibe as the risk of myopathy. If possible, it is necessary to use other drugs (not interact with atorvastatin) instead of the above.

If simultaneous treatment with atorvastatin and the aforementioned drugs is necessary, the benefits and risks of simultaneous treatment should be carefully weighed. If patients take medications that increase the concentration of atorvastatin in blood plasma, it is recommended to reduce the dose of atorvastatin to a minimum. In addition, in the case of the use of potent inhibitors of CYP3A4, a lower initial dose of atorvastatin should be considered. It is also recommended that proper clinical monitoring of the condition of these patients be carried out.

It is not recommended to simultaneously appoint atorvastatin and fusidic acid, so it is worth considering the temporary withdrawal of atorvastatin during treatment with fusidic acid.

Interstitial lung disease

During treatment with some statins (especially during long-term treatment), exceptional cases of interstitial lung disease development have been described. To manifestations of this disease include shortness of breath, unproductive cough and general deterioration of health (fatigue, weight loss and fever). In case of suspicion of interstitial lung disease, treatment with statins should be discontinued.

Fillers

The composition of the drug atorvastatin Ananta is lactose. This drug should not be taken to patients with rare hereditary diseases associated with galactose intolerance, Lappease lactase deficiency, or malabsorption of glucose-galactose.Therapy lipidomodifikatsiiimy drugs should be one of the components of complex therapy for patients with a significantly increased risk of atherosclerotic vascular disease through hypercholesterolemia. Drug therapy is recommended as a supplement to a diet, when the result of adherence to a diet that restricts the intake of saturated fats and cholesterol, as well as from the use of other non-medicament measures was not enough. Patients with coronary heart disease or with several risk factors for developing coronary heart disease can take Atorvastatin Anant at the same time as dieting.

Restriction of use

Atorvastatin was not investigated under conditions when the main deviation from the norm from lipoproteins is an increase in the level of chylomicrons (types I and V according to Fredrickson classification).

Use during pregnancy and lactation

Atorvastatin Ananta is contraindicated during pregnancy, to women planning a pregnancy or in case of high probability of conception of the child as a result of insufficient measures of protection. Statins can harm the fetus when administered to pregnant women. Atorvastatin Ananta can be used in women of reproductive age only if it is very unlikely that such patients will become pregnant and have been informed of potential risk factors. Women of reproductive age should apply appropriate contraceptive measures. If during treatment the patient decides to become pregnant, she should stop taking the drug no later than a month before the planned pregnancy. If a woman becomes pregnant during the treatment period of Atorvastatin Ananta, the drug should be discontinued immediately and the patient should be re-advised on potential risk factors for the fetus and there is no known clinical benefit from continuing the drug during pregnancy.

With a normal course of pregnancy, serum cholesterol and triglyceride levels increase. Admission of lipid-lowering drugs during pregnancy will not have a beneficial effect, since cholesterol and its derivatives are necessary for normal fetal development. Atherosclerosis is a chronic process, and, consequently, a break in taking lipid-lowering drugs during pregnancy should not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.

Adequate and well-controlled studies of the use of atorvastatin in pregnancy have not been conducted. There are data on congenital anomalies after intrauterine exposure to statins. In pregnant women treated with other drugs of the statin group, the incidence of congenital fetal abnormalities, miscarriages and fetal deaths / stillbirths did not exceed the frequency expected for the general population. However, 89% of these cases began before pregnancy and stopped at the first trimester after pregnancy was detected.

It is not known whether atorvastatin penetrates breast milk, but it is known that a small amount of another drug of this class penetrates into breast milk. Because statins are potentially capable of causing serious adverse reactions in infants who are breastfeeding, women who need treatment with Atorvastatin Ananta should not breast-feed their infants (see Section "Contraindications").

The ability to influence the reaction rate when driving vehicles or other mechanisms

Has very little effect on the reaction rate when driving vehicles or working with other mechanisms.

Dosing and Administration

Before starting therapy with atorvastatin, Ananta should determine the level of hypercholesterolemia against the background of the appropriate diet, prescribe physical exercises and measures to reduce the body weight of obese patients, and treat other diseases. During treatment with atorvastatin Ananta, patients should follow a standard diet with low cholesterol. Apply the drug at a dose of 10-80 mg once a day every day, at any time of the day, regardless of food intake. The starting and maintenance dose can be individualized according to the initial level of LDL-C, the objectives of therapy and its effectiveness. After 2-4 weeks after the start of treatment and / or correction of the dose of atorvastatin Anant, a lipidogram should be determined and the dose adjusted according to it.

Primary hypercholesterolemia and combined (mixed) hyperlipidemia. The recommended initial dose of atorvastatin Anant is 10 or 20 mg once a day. For patients who require a significant reduction in LDL cholesterol (more than 45%), therapy can be started at a dosage of 40 mg once a day. The dosage range of the drug Atorvastatin Anant is in the range of 10 to 80 mg once daily. The drug can be taken in a single dose at any time and regardless of food intake. Initial and maintenance doses of atorvastatin Ananta should be selected individually, depending on the purpose of treatment and response. After starting treatment and / or after titrating the dose of atorvastatin, Ananta should analyze the lipid levels for a period of 2 to 4 weeks and adjust the dose accordingly.

Homozygous familial hypercholesterolemia. The dose of atorvastatin Anant for patients with homozygous familial hypercholesterolemia is 10 to 80 mg per day, which reduces the LDL-C level by more than 15% (18-45%). Atorvastatin Ananta should be used as an adjunct to other lipid-lowering treatments (eg, LDL apheresis), or if lipid-lowering treatments are not available.

Heterozygous familial hypercholesterolemia in pediatric practice (10-17 year old patients). It is recommended to prescribe Atorvastatin Ananta in a starting dose of 10 mg once a day daily. The maximum recommended dose is 20 mg 1 time per day daily (doses exceeding 20 mg have not been studied in patients in this age group). The dose can be individualized in accordance with the objectives of therapy, dose adjustment can be done at intervals of 4 weeks or more.

Dosing for patients with impaired renal function. Kidney disease does not affect the concentration of atorvastatin or a decrease in the level of LDL cholesterol in the blood plasma. Therefore, there is no need for dose adjustment.

Simultaneous lipid-lowering therapy

Atorvastatin Ananta can be used with SECTIONS of bile acids. The combination of inhibitors of HMG-CoA reductase (statins) and fibrates should generally be used with caution (see Sections "Features of Use", "Interaction with Other Drugs and Other Interactions").

Patients of advanced age. Differences in safety, effectiveness, or achievement of the goal in the treatment of hypercholesterolemia in elderly patients and patients of other age groups do not.

Dosage for patients taking cyclosporine, clarithromycin, itraconazole, or certain protease inhibitors

Treatment with atorvastatin should be avoided in patients who take cyclosporine or HIV protease inhibitors (tipranavir + ritonavir), or a protease inhibitor of hepatitis C virus (telaprevir). Atorvastatin should be used with caution in patients with HIV who take lopinavir + ritonavir and apply it in the most appropriate dose. In patients taking clarithromycin, itraconazole, or in patients with HIV who are taking saquinavir + ritonavir, darunavir + ritonavir, fosamprenavir, or fosamprenavir + ritonavir in combination, the therapeutic dose of atorvastatin Anant should be limited to a dose of 20 mg, to ensure the application of the slightest necessary dose of atorvastatin Ananta. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, treatment with atorvastatin Ananta should be limited to a dose of up to 40 mg, and appropriate clinical trials are recommended to ensure the use of the smallest required dose of atorvastatin Anant (see Section "Application Specificities" and "Interaction with other drugs and other types of interactions").

Children

In patients aged 10-17 years with heterozygous familial hypercholesterolemia, namely, in teenage boys and girls after the onset of menstruation, no significant effect of the drug on the growth or puberty of boys or on the duration of the menstrual cycle in girls was found (see Sections reactions "," Method of administration and dose "). Adolescent girls should be advised on acceptable contraceptive methods during the treatment period of Atorvastatin Ananta (see Section "Use during pregnancy or lactation").

The efficacy and safety of the use of atorvastatin for the treatment of children under 10 years of age has not been studied. Therefore, the use of the drug for the treatment of patients of this age group is not recommended.

Overdose

There is no specific treatment for atorvastatin overdose. In case of an overdose, the patient should be treated symptomatically and, if necessary, using supportive measures. Due to the high degree of drug binding to plasma proteins, no significant increase in atorvastatin clearance by hemodialysis should be expected.

Adverse Reactions

Atorvastatin generally well tolerated.

The undesirable reactions include:

  • general disorders: chest pain, facial edema, fever, asthenia, neck stiffness, weakness, photosensitivity, generalized edema, malaise, pyrexia, peripheral edema
  • nervous system: insomnia, dizziness, paresthesia, drowsiness, amnesia, sleep disturbance, nightmares, decreased libido, emotional lability, impaired coordination, peripheral neuropathy, torticollis, facial paralysis, hyperkinesia, depression, hypoesthesia, hypertension, headache, dysgeusia;
  • from the gastrointestinal tract: gastroenteritis, impaired liver function, colitis, vomiting, nausea, gastritis, dry mouth, rectal hemorrhage, esophagitis, glossitis, oral ulcers, anorexia, increased appetite, stomatitis, cheilitis, duodenal ulcers, Dysphagia, enteritis, grinded, gum bleeding, stomach ulcers, tenesmus, ulcerative stomatitis, hepatitis, pancreatitis, hepatitis, cholestatic jaundice, diarrhea, abdominal pain, indigestion, constipation, flatulence, epigastric discomfort, belching, cholestasis,
  • From the musculoskeletal system and connective tissue: arthritis, myopathy, myalgia, myositis, muscle cramps;bursitis, tendosynovitis, myasthenia gravis, tendon contracture, musculoskeletal pain, muscle spasms, increased muscle fatigue, neck pain, swelling of the joints, tendinopathy (sometimes difficult to rupture of the tendon), joint pain, back pain
  • from the side of metabolism and nutrition: peripheral edema, hyperglycemia, increased levels of CK, gout, weight gain, hypoglycemia, anorexia, increased transaminases, abnormalities in functional liver samples, increased alkaline phosphatase levels in the blood
  • from the liver and gallbladder: liver failure
  • skin and connective tissue: alopecia, itching, contact dermatitis, dry skin, increased sweating, acne, urticaria, eczema, seborrhea, skin ulcers, rash, angioedema, bullous dermatitis (including erythema multiforme), Stevens Johnson syndrome and toxic epidermal necrolysis
  • from the respiratory system, chest and mediastinum: sore throat and larynx, bronchitis, rhinitis, pneumonia, dyspnea, asthma, epistaxis, nasopharyngitis;
  • On the part of the blood system and lymphatic system: ecchymosis, anemia, lymphadenopathy, thrombocytopenia, petechiae;
  • from the side of the immune system: allergic reactions of anaphylaxis;
  • from the sense organs: amblyopia, parosmia, loss of taste, perversion of taste;
  • from the side of vision: blurred vision, visual impairment, dry eyes, refraction, cataracts, eye hemorrhages, glaucoma, blurred vision;
  • from the organs of hearing and balance: noise in the ears, deafness;
  • from the part of the urinary and reproductive systems: infection of the urinary system, hematuria, albuminuria, frequent urination, cystitis, dysuria, urolithiasis, nocturia, epididymitis, mastopathy, vaginal bleeding, uterine bleeding, enlargement of the mammary glands, metrorrhagia, nephritis, urinary incontinence, urinary retention , acute urinary retention, impotence, ejaculation disorders, leukocyturia, gynecomastia
  • from the cardiovascular system: palpitation, vasodilation, syncopal conditions, migraine, postural hypotension, phlebitis, arrhythmia, angina attack, hypotension
  • changes in the results of laboratory tests: often deviations in the results of functional liver samples, increased activity of the blood CKK is not often a positive result of the analysis on the content of leukocytes in the urine.

Pediatric patients (10-17 years). In patients receiving atorvastatin, there were side effects, similar manifestations in patients in the placebo group. The most common adverse event that was observed in both groups, not counting the causal relationship, was infection.

In the postmarketing period, there were such side effects: thrombocytopenia, allergic reactions (including anaphylaxis), angioedema, weight gain; hypnosis, amnesia, dizziness, ringing in the ears Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, bullous eruptions, urticaria rhabdomyolysis, tendon rupture, arthralgia, back pain chest pain, peripheral edema, malaise, fatigue, dysgeusia, headache pain, abdominal pain, tinnitus, peripheral edema, increased activity of alanine aminotransferase, increased activity of CKK blood.

Shelf life

3 years.

Storage conditions

Store in the original packaging at a temperature not higher than 30 ° C. Keep out of the reach of children.

Packaging

For 10 tablets in blisters, 3 blisters per box.

Category of leave

On prescription.

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