Astin 20 mg tablets №30
|Amount in a package||30|
|Manufacturer||Micro Labs (India)|
|The main medicament||Astin|
Astin (ASTIN) user's manual
active ingredient: atorvastatin; 1 tablet contains atorvastatin calcium equivalent to 10 mg or 20 mg of atorvastatin;
auxiliary substances: calcium carbonate, lactose, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, talc, magnesium stearate, sodium hydrogen carbonate, hypromellose, polyethylene glycol 400, titanium dioxide (E 171), iron oxide yellow (E172), iron oxide red (E172 ).
Basic physical and chemical properties:
tablets 10 mg: tablets covered with a film coating of brown-orange color, round, biconvex;
20 mg tablets: tablets covered with a film coating of brown-orange color, round, biconvex, with a notch on one side.
Drugs that lower the level of cholesterol and triglycerides in the blood serum. Inhibitors of HMG-CoA reductase.ATX Code C10A A05.
Atorvastatin is a lipid-lowering drug, a selective competitive inhibitor of HMG-CoA reductase.
More effective than other groups of statins. In patients with hypercholesterolemia and hypertriglyceridemia, it effectively reduces total cholesterol (by 30-46%), LDL cholesterol (by 41-61%), triglycerides (by 14-33%), apolipoprotein B (by 34-50%) in serum , promotes an increase in the level of HDL cholesterol (high-density lipoproteins) and apolipoprotein A-1.These results are recorded in patients with heterozygous familial hypercholesterolemia and mixed hyperlipidemia, including patients with insulin-dependent diabetes mellitus.
Numerous clinical studies have shown that elevated levels of total cholesterol, LDL cholesterol and apo B (a membrane complex for LDL cholesterol) provoke the development of atherosclerosis. Similarly, the levels of HDL cholesterol (and its transport complex - a for A) are lowered due to the development of atherosclerosis. Epidemiological studies have established that cardiovascular morbidity and mortality change in direct proportion to the level of total cholesterol and LDL cholesterol and inversely proportional to the level of HDL cholesterol.
The primary therapeutic effect is usually noted within 2 weeks from the start of treatment, the maximum - after 4 weeks, which persists with constant maintenance therapy. The lowering of LDL cholesterol level largely depends on the dose of the drug than on its systemic concentration.
After ingestion, atorvastatin is rapidly absorbed in the digestive tract, the degree of absorption increases proportionally to the dose. The maximum concentration in plasma (C max) is achieved after 1-2 hours. Bioavailability is low (about 14%), the systemic bioavailability of inhibitory activity against HMG-CoA reductase is about 30%. The use of the drug together with food reduces the rate and extent of absorption of atorvastatin by approximately 25% and 9%, respectively, but this does not significantly affect the severity of its hypolipidemic effect. At least 98% of atorvastatin binds to blood plasma proteins. Metabolism. Atorvastatin is metabolized by cytochrome P450 ZA4 to active ortho and para-hydroxylated metabolites, with which about 70% of its pharmacological activity is associated.
Conclusion. Atorvastatin and its metabolites are excreted mainly with bile; less than 2% - is excreted in the urine. The half-life of atorvastatin is approximately 14 hours, but the half-life of the inhibitory effect on HMG-CoA reductase is 20-30 hours due to the action of active metabolites.
The hypolipidemic effects of atorvastatin do not differ significantly in patients of different age groups, despite the fact that when taking in equal doses, its maximum concentration and area under the concentration-time curve (AUC) in healthy volunteers of the older age group (over 65 years) than in young patients. In women, the maximum concentration of atorvastatin in blood plasma is 20% higher, and the AUC value is 10% lower than that of men, but there is no difference in the effect on the degree of LDL cholesterol reduction in the treatment of atorvastatin in both sexes.
With kidney disease, the degree of lowering LDL cholesterol in the blood plasma under the influence of atorvastatin does not change, which does not require dose adjustment for such patients. Hemodialysis, most likely, there is no significant stimulating effect on the clearance of atorvastatin, since the drug is largely associated with plasma proteins.The concentration of atorvastatin in the blood plasma can sharply (4-16 times) increase in patients with cirrhosis and some other severe liver diseases.
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 coronary heart disease in a family history, Astin is shown for:
- reduction in the risk of myocardial infarction
- reducing the risk of stroke;
- reduction in 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, Astin is indicated for:
- reduction in the risk of myocardial infarction
- reduction of the risk of stroke.
For patients with clinically severe ischemic heart disease, Astin 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.
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 cardiovascular disease
are present in a child of child age.
Astin is contraindicated in patients with hypersensitivity to the components of the drug, liver disease in the acute phase, or with persistent elevation (unknown genesis) of serum transaminase levels by three or more times.
Interaction with other drugs and other interactions
The risk of myopathy during treatment with HMG-CoA reductase inhibitors is enhanced by the simultaneous use of cyclosporine, fibrates, nicotinic acid or cytochrome P450 inhibitors of ZA4 (eg, erythromycin, azole antifungal drugs).
Inhibitors of cytochrome P450.
Atorvastatin is metabolized by cytochrome P450 AP4. Simultaneous use of atorvastatin with cytochrome P450 inhibitors of ZA4 can lead to an increase in the concentration of atorvastatin in the blood plasma. The strength of the interaction and the potentiation of the effect depends on the variability of the action on cytochrome P450 ZA4.
Atorvastatin and atorvastatin metabolites are substrates of the OATP1B1 transporter. Inhibitors of OATP1B1 (eg, cyclosporin) may increase the bioavailability of atorvastatin. Simultaneous use of 10 mg of atorvastatin and cyclosporine (5.2 mg / kg / day) leads to an increase in exposure to atorvastatin 7.7 times. Avoid simultaneous application of Astin and cyclosporine (see section "Features of application").
Erythromycin / clarithromycin
With the simultaneous use of atorvastatin and erythromycin (500 mg four times a day) or clarithromycin (500 mg twice daily), which are inhibitors of cytochrome P450 3A4, the concentration of atorvastatin in the blood plasma increases.
As a result of simultaneous use of atorvastatin and protease inhibitors, the well-known inhibitors of cytochrome P450 ZA4, the concentration of atorvastatin in the blood plasma is increased.
Simultaneous administration of atorvastatin (40 mg) and diltiazem (240 mg) is accompanied by an increase in the concentration of atorvastatin in the blood plasma.
Gemfibrozil. In view of the increased risk of myopathy / rhabdomyolysis with concomitant use of HMG-CoA reductase inhibitors with gemfibrozil, joint use of Astin 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 is increased with simultaneous administration of other fibrates, Astin should be used with caution when used in conjunction with other fibrates (see Section "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 Astin should be considered (see Section "Features of Use").
No evidence of interaction between atorvastatin and cimetidine has been identified.
Simultaneous use of atorvastatin (20 and 40 mg) and itraconazole (200 mg) was accompanied by an increase in the atorvastatin AUC
Contains one or more components, inhibits CYP3A4 and can increase the concentration of atorvastatin in blood plasma, especially when consuming juice more than 1.2 liters / day.
Rifampicin or other inducers of cytochrome P450 3A4.
The simultaneous administration of atorvastatin and cytochrome P450-ZA4 inducers (eg, efavirenz, rifampin) can lead to an unstable decrease in the concentration of atorvastatin in the blood plasma. Taking into account the double mechanism of action of rifampin (induction of cytochrome P450 ZA4 and inhibition of the transporter enzyme OATP1B1 in the liver), it is recommended to prescribe atorvastatin concomitantly with rifampin, since taking atorvastatin after taking rifampin leads to a decrease in the level of atorvastatin in the blood plasma.
Simultaneous oral administration of atorvastatin and oral suspension of an antacid preparation containing magnesium and aluminum hydroxide is associated with a 35% reduction in atorvastatin levels in plasma. In this case, the hypolipidemic effect of atorvastatin is unchanged.
Due to the fact that atorvastatin does not affect the pharmacokinetics of antipyrin, the possibility of interaction with other drugs that are absorbed by the same cytochrome isoenzymes is considered unlikely.
The concentration of atorvastatin in the blood plasma is lower (by approximately 25%) with simultaneous administration of atorvastatin and colestipol. In this case, the hypolipidemic effect of the combination of atorvastatin and colestipol exceeded the effect that gives the reception of each of these drugs separately.
Studies of the interaction of atorvastatin and fusidic acid have not been conducted. As in the case of other statins, in the postmarketing period with the simultaneous administration of atorvastatin and fusidic acid, phenomena from the muscular system (including rhabdomyolysis) were observed. The mechanism of this interaction remains unknown.Patients need careful monitoring; temporary suspension of treatment with atorvastatin may be required.
Multiple simultaneous administration of digoxin and 10 mg of atorvastatin was not accompanied by an increase in the equilibrium concentration of digoxin in the blood plasma. At the same time, the use of digoxin and 80 mg of atorvastatin led to an increase in the digoxin concentration by about 20%. Patients taking digoxin should be under appropriate supervision.
The simultaneous administration of atorvastatin (10 mg per day) and azithromycin (500 mg once a day) was not accompanied by changes in the concentration of atorvastatin in the blood plasma.
The simultaneous use of atorvastatin and oral contraceptives, which include
norethisterone and ethinyl estradiol, was accompanied by an increase in AUC for these components by 30% and 20%, respectively. This fact of increase should be considered when choosing an oral contraceptive for women taking atorvastatin.
Clinically significant interaction of atorvastatin with warfarin was not revealed.
In healthy subjects, simultaneous use of 80 mg of atorvastatin and 10 mg of amlodipine was accompanied by an 18% increase in the concentration of atorvastatin in blood plasma and was not clinically significant.
Colchicine. With the simultaneous use of atorvastatin with colchicine, there have been reports of cases of myopathy, including rhabdomyolysis, so caution should be given to atorvastatin with colchicine.
Inhibitors of transport proteins
Inhibitors of transport proteins (eg, cyclosporin) are able to increase the level of systemic exposure to atorvastatin. The effect of inhibition of storage transport proteins on the concentration of atorvastatin in the liver cells is unknown. If simultaneous administration of these drugs is not possible, dose reduction and clinical monitoring of the efficacy of atorvastatin should be recommended.
The use of ezetimibe as monotherapy is associated with the development of phenomena from the muscular system, including rhabdomyolysis. Thus, with the simultaneous use of ezetimibe and atorvastatin, the risk of developing these phenomena increases. It is recommended to conduct proper clinical monitoring of the condition of such patients.
Clinical studies have shown that simultaneous use of atorvastatin and antihypertensive drugs and their use in estrogen replacement therapy were not accompanied by clinically significant side effects. Studies of interaction with other drugs have not been conducted.
Atorvastatin, like other preparations of the statin group, sometimes causes myopathy, which is defined as muscle pain or muscle weakness, combined with an increase in CKK (CK) values of more than 10 times the upper limit of the norm.Simultaneous use of high doses of atorvastatin with certain medications, such as cyclosporine and potent CYP3A4 inhibitors (eg clarithromycin, itraconazole and HIV protease inhibitors) increases the risk of myopathy / rhabdomyolysis.
There were rare reports of cases of immunologically mediated necrotizing myopathy (IONM) - autoimmune myopathy associated with the use of statins. IONM is characterized by the following symptoms: weakness of proximal muscles and elevated serum CK levels, which persist despite the cessation of statin treatment; muscle biopsy reveals necrotizing myopathies without significant inflammation; when immunosuppressive agents are used, a positive trend is observed.
The possibility of developing myopathy should be considered in any patient with diffuse myalgias, tenderness or weakness of the muscles and / or a significant increase in CK. Patients should be advised immediately to report muscle pain, tenderness, or weakness in the muscles of unknown etiology, especially if it is accompanied by a feeling of malaise or fever, or if signs and symptoms of muscle disease persist after discontinuing Astin. Treatment should be discontinued in the event of an increase in the level of CK, 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 the possibility of combination drug therapy Astin 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.
It reported cases of myopathy, including rhabdomyolysis, while the use of atorvastatin with colchicine, so atorvastatin with colchicine should be administered with caution to patients (see. Section "Interaction with other medicinal products and other forms of interaction").
Therapy Astin, temporarily or completely stop any patient with an acute, serious condition, indicates the development of myopathy, or if there is a risk factor for renal disease development due to rhabdomyolysis (eg severe acute infection, hypotension, surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).
Abnormal liver function
Before starting therapy with Astin, 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 Astin preparation. If an alternate etiology is not defined, do not re-start the treatment with the drug.
Astin should be used with caution in patients taking significant amounts of alcohol and / or have a history of liver disease. Astin contraindicated with active liver disease or persistent elevations in liver transaminases of unknown etiology (see. Section: "Contra ').
It reported an increased level of HbA1c concentration and serum fasting glucose when using the HMG-CoA reductase inhibitors.
Statins inhibit cholesterol synthesis and theoretically may reduce the secretion of adrenal and / or gonadal steroids. 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 indeed 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
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 patients receiving atorvastatin 80 mg compared with placebo group (55 cases 2.3 % in the atorvastatin group compared to 33 cases, 1.4% in the placebo group; p: 1.68, 95% CI: 1,09, 2,59; p = 0,0168). The incidence of fatal hemorrhagic stroke were similar in all treatment groups (17 and 18 for atorvastatin and placebo groups, respectively). The incidence of non-fatal hemorrhagic stroke was significantly greater in patients treated with atorvastatin (38, 1.6%) compared with the placebo group (16, 0.7%). Some of the initial characteristics,including the presence of cases of hemorrhagic stroke and lacunar during inclusion in the study, it has been associated with a higher incidence of hemorrhagic stroke patients receiving atorvastatin (see. Section "Adverse reactions").
Since older age (65 years) is a factor of predisposition to myopathy, should be used with caution in elderly Astin.
Astin contraindicated in patients with active liver disease, including persistent elevation of liver transaminases of unknown etiology (see. Sections "Contra" and "Pharmacological properties").
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
- 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 (over 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.
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 you want to carry out simultaneous treatment with atorvastatin and mentioned drugs should carefully weigh the benefits and risks of simultaneous treatment. If patients are taking medicines that increase the concentration of atorvastatin in plasma, it is recommended to reduce the dose of atorvastatin to a minimum. Furthermore, in the case of strong CYP3A4 inhibitors should consider the possibility of using a lower initial dose of atorvastatin. It is also recommended to carry out a proper clinical monitoring of the condition of these patients.
It is not recommended to appoint both atorvastatin and fusidic acid, so it is worth considering the possibility of temporary suspension of atorvastatin during fusidic acid treatment.
Interstitial lung disease
During treatment certain statins (especially during long-term treatment) were disclosed exceptional cases of interstitial lung disease. By manifestations of the disease may include dyspnea, nonproductive cough and general health deterioration (fatigue, weight loss and fever). In the event of a suspicion of interstitial lung disease should discontinue treatment with statins.
The composition Astin preparation includes lactose. This drug should not be taken in patients with rare hereditary diseases associated with galactose intolerance, Lapp lactase deficiency or impaired glucose-galactose malabsorption. Therapy lipidomodifikatsiynimy drugs should be one of the constituents of complex therapy for patients with significantly increased risk of atherosclerotic vascular disease through hypercholesterolemia. Drug therapy is recommended as an adjunct to diet when the result of dieting, limiting the intake of saturated fats and cholesterol, as well as the use of other non-drug measures were not enough.Patients with coronary heart disease or multiple risk factors for coronary heart disease of the drug Astin can start simultaneously with dieting.
Astin not investigated under conditions where the main aberration by the lipoprotein is a chylomicron raising (types I and V Fredrickson classification).
Use during pregnancy and lactation
Astin is contraindicated in pregnant women and women who may become pregnant. Statins can cause harm to the fetus when applied to pregnant women. Astin can be applied to women of childbearing age only when it is highly unlikely that such patients become pregnant, and they were informed of the potential risk factors. If a woman becomes pregnant during treatment Astin, you should immediately stop taking the drug and re-advise the patient of the potential risk to the fetus and there is no known clinical benefit to continue taking the drug during pregnancy.
When normal pregnancy levels of serum cholesterol and triglycerides increased. Receiving hypolipidemic drugs during pregnancy will not be useful effect as cholesterol and its derivatives necessary for normal fetal development. Atherosclerosis - a chronic process, and therefore, a break in the reception of lipid-lowering drugs during pregnancy should not have a significant impact on the long-term treatment of primary hypercholesterolemia.
Adequate and well-controlled trials of atorvastatin during pregnancy was not performed. There have been rare reports of congenital anomalies following intrauterine exposure to statins. When a prospective observation of approximately 100 cases of pregnancy in women treated with other medications group of statins, the incidence of congenital anomalies of the fetus, miscarriage and fetal death / stillbirths not exceed the frequency expected for the general population. However, this study could only exclude 3-4 fold increase in the risk of congenital anomalies of the fetus as compared with the background rate. In 89% of these cases, the treatment started before pregnancy and stopped when I trimester pregnancy after detection.
Unknown, it permeates atorvastatin passes into breast milk, but it is known that a small amount of another drug in this class passes into breast milk. Since statins have the potential to cause serious adverse reactions in infants who are breastfed, women who need treatment with atorvastatin should not breast feed their infants (see. "Contraindications").
Ability to influence the reaction rate when driving or operating other machinery.
It carries very little impact on the rate of reaction when driving or operating other machines.
Dosing and Administration
Hyperlipidemia (heterozygous familial and non-family) and mixed dyslipidemia (IIa and type IIb Fredrickson classification).
The recommended starting dose is 10 mg astynom or 20 mg 1 time per day. For patients that require a significant reduction in LDL cholesterol levels (more than 45%), the therapy may be initiated with dosages of 1 to 40 mg once a day. Dosing of the drug is in the range between 10 and 80 mg 1 time per day. Astin should be taken 1 time per day, at any time of the day, regardless of meals. Starting and maintenance dose is adjusted individually. After 2-4 weeks of treatment and / or post-titration dose astynom check lipoprotein level and, depending on the analysis results, correct dose.
Heterozygous familial hypercholesterolemia in pediatric patients (10-17- year-old patient).
It is recommended to prescribe Astin in an initial dose of 10 mg once a day. The maximum recommended dose is 20 mg once a day (doses exceeding 20 mg have not been studied in patients in this age group). Dose to determine individually, depending on the purpose of treatment. Every 4 weeks or more, you need to adjust the dose of the drug.
Homozygous familial hypercholesterolemia. The dose of Astin for patients with homozygous familial hypercholesterolemia ranges from 10 to 80 mg per day. Astin should be used as an adjunct to other lipid-lowering treatments (eg, LDL apheresis), or if lipid-lowering treatments are not available.
Simultaneous lipid-lowering therapy
Astin can be used with SECTIONAL BILLS. 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").
Dosing for patients with impaired renal function
Kidney disease does not affect the concentration in the blood plasma, or to reduce the level of LDL cholesterol when using Astin; consequently, correction of the dose of the drug for patients with impaired renal function is unnecessary (see the sections "Features of application", "Pharmacokinetics").
Dosage for patients taking cyclosporine, clarithromycin, itraconazole, or certain protease inhibitors
Astin treatment should be avoided for patients who take cyclosporine or HIV protease inhibitors (tipranavir + ritonavir), or hepatitis C virus protease inhibitor (telaprevir). Astin should be used with caution in patients with HIV who take lopinavir + ritonavir and apply 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 Astin should be limited to a 20 mg dose, and it is also recommended that the necessary clinical ensuring the application of the slightest necessary dose of Astin. In patients taking a protease inhibitor HIV nelfinavir or a protease inhibitor of hepatitis C virus boceprevir, Astin treatment should be limited to a dose of up to 40 mg, and it is also recommended that appropriate clinical examinations be performed to ensure the application of the smallest required Astin dose (see Section "Features of Use" and "Interaction with other drugs and other types of interactions ").
Controlled clinical trials of atorvastatin in patients under 10 years of age with heterozygous familial hypercholesterolemia were not performed. Children aged 10 years or older are used according to the indications indicated in the "Indications" section.
There is no specific treatment for an overdose of Astin. In cases of drug overdose, if necessary, conduct symptomatic and supportive therapy. Due to the high degree of binding of the drug to plasma proteins, we should not expect a significant increase in the clearance of Astin with hemodialysis.
Due to the fact that clinical studies are conducted in conditions that fluctuate widely, the incidence of adverse reactions observed during clinical trials of the drug can not be directly compared to those obtained from clinical studies of another drug and they may not reflect frequency indicators are observed in clinical practice.
The table summarizes the incidence of clinical adverse events, regardless of causation, recorded in 2% of patients or more and at a frequency higher than in placebo in patients, according to 17 placebo-controlled studies.
|Unwanted reaction *||Any dose of N = 8755||10 mg N = 3908||20 mg N = 188||40 mg N = 604||80 mg N = 4055||Placebo N = 7311|
|Pain in the extremities||6th||8.5||3.7||9.3||3.1||5.9|
|Urinary tract infection||5.7||6.9||6.4||8||4.1||5.6|
* Unwanted reaction> 2% at any dose greater than placebo
Other undesirable reactions reported during placebo-controlled studies include:
general disorders: malaise, pyrexia;
from the digestive system: gastrointestinal discomfort, belching, flatulence, hepatitis, cholestasis,
From the musculoskeletal system: musculo-skeletal pain, increased fatigue of muscles, neck pain, swelling of the joints, tendinopathy (sometimes it is difficult to rupture the tendon) from the side of metabolism and nutrition: increased transaminases, deviations from the norm of functional liver tests, increased levels alkaline phosphatase in the blood, increased activity of CK, hyperglycemia;
from the side of the nervous system: nightmarish dreams;
from the respiratory system: nosebleeds;
From the skin and subcutaneous tissue: urticaria
on the part of the organs of vision: blurred vision, impaired vision;
from the organs of hearing and balance: tinnitus
from the genitourinary system: leukocyturia;
On the part of the reproductive system and mammary glands: gynecomastia.
The incidence of adverse reactions was determined as follows: often (> 1/100, <1/10); infrequently (> 1/1000, <1/100);rare (> 1/10000, <1/1000); very rare (<1/10000).
Violation of the function of the nervous system: often headache infrequent: dizziness, paresthesia, hypoesthesia, dysgeusia, amnesia, rare: peripheral neuropathies.
From the gastrointestinal tract: often constipation infrequently pancreatitis, vomiting.
From the osteomuscular system and connective tissue: often joint pain, back pain are rare: myopathy, myositis, rhabdomyolysis.
Common disorders: infrequent asthenia, chest pain, peripheral edema, increased fatigue.
From the side of metabolism and nutrition: infrequently hypoglycemia, weight gain, anorexia.
From the liver and gallbladder: extremely rare: liver failure.
From the skin and connective tissue: skin rashes, itching, alopecia rare angioedema, bullous dermatitis (including erythema multiforme), Stevens-Johnson syndrome and toxic epidermal necrolysis.
From the respiratory system, chest and mediastinum: often: sore throat and larynx.
On the part of the blood system and lymphatic system: rare: thrombocytopenia.
From the immune system: often allergic reactions; extremely rare: anaphylaxis.
From the side of the organ of vision: infrequent blurring of vision.
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 for the content of leukocytes in the urine.
As with the use of other inhibitors of HMG-CoA reductase, an increase in serum transaminase activity was observed in patients taking atorvastatin. These changes were usually mild, temporary and did not require intervention or treatment.Clinically significant increase in serum transaminase activity (exceeding the upper limit of the norm by more than 3 times) was observed in 0.8% of patients taking atorvastatin. This increase should be dose-dependent and reversible in all patients.
In 2.5% of patients taking atorvastatin, an increase in serum CK activity was observed, which was more than 3 times the upper limit of the norm. This is consistent with observations with other HMG-CoA reductase inhibitors in clinical trials. In 0.4% of patients receiving atorvastatin, a level exceeding the upper limit of the norm was observed more than 10 times.
Adverse reactions that occurred during clinical trials: urinary tract infection, diabetes, stroke.
Experience in the post-marketing use of the drug.
During the post-marketing use of the drug, the following adverse reactions were observed. Since these reactions are reported on a voluntary basis from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a cause-and-effect relationship with the use of the drug.
To undesirable reactions registered after the release of the drug on the market, regardless of the evaluation of the cause-effect relationship, include the reactions: anaphylaxis, angioedema, bullous rash (including exudative erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), rhabdomyolysis, increased fatigue, rupture of the tendon, lethal and non-lethal hepatic insufficiency, dizziness, depression, peripheral neuropathy and pancreatitis.
There were rare reports of cases of immunologically mediated necrotizing myopathy associated with the use of statins (see Section "Features of application").
There have been rare post-registration reports of cognitive impairment (eg memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with the use of statins. These cognitive disorders were recorded with all statins. The reports generally did not belong to the category of serious adverse reactions and these manifestations were reversible after discontinuation of taking statins, with different time to the onset of the symptom (from 1 day to several years) and the disappearance of the symptom (median duration was 3 weeks).
When using some statins, such undesirable phenomena have been described: a disorder of sexual function; exceptional cases of interstitial lung disease, especially during prolonged treatment.
During post-marketing observations, the following adverse reactions were reported.
From the function of the circulatory and lymphatic system: thrombocytopenia.
From the function of the immune system: allergic reactions, anaphylactic shock (including anaphylactic shock).
From the side of metabolism and nutrition: an increase in body weight.
From the side of the function of the nervous system: headache, hypoesthesia, dysgeusia.
From the gastrointestinal tract: abdominal pain.
From the function of the organs of hearing and balance: noise in the ears.
From the skin and subcutaneous tissue: urticaria.
From the musculoskeletal system and connective tissue: arthralgia, back pain.
Common disorders: chest pain, peripheral edema, malaise, increased fatigue.
Changes in the results of laboratory tests: increased activity of alanine aminotransferase, increased activity of CKK blood.
Children (10-17 years)
In patients receiving atorvastatin, adverse reactions were observed, similar to those observed in patients receiving placebo. The most common side effects observed in both groups, not taking into account the causal relationship, were infections.
Store in the original packaging at a temperature not higher than 25 ° C. In a place inaccessible to children.
10 tablets in a blister, 3 blisters in a cardboard box.
Category of leave