Atorvastatin Teva coated pills 10mg N30
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Active ingredients
Atorvastatin
Release form
Pills
Composition
Atorvastatin calcium 10.36 mg, which corresponds to the content of atorvastatin 10 mg.; Excipients: lactose monohydrate - 94.94 mg, povidone - 4 mg, Eudragit E100 (copolymer of butyl methacrylate, dimethylaminoethyl methacrylate and methyl methacrylate 1: 2: 1) - sam, I-a-one, I-a-one, I-a-one, I-a-one, I-a-one, I-a-one, I'll have a weight of 1: 2; - 3 mg, croscarmellose sodium - 5 mg, sodium stearyl fumarate - 1.2 mg, opadry YS-1R-7003 (titanium dioxide - 0.9375 mg, hypromellose 2910 3cP (E464) - 0.8963 mg, hypromellose 2910 5cP (E464) - 0.8963 mg, macrogol 400 - 0.240 mg, polysorbate 80 - 0.030 mg).
Pharmacological effect
A lipid-lowering drug, a selective competitive inhibitor of HMG-CoA reductase, an enzyme that determines the maximum rate of cholesterol biosynthesis (Xc), responsible for the conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A to mevalonate, the precursor of sterols, including Xc. In the liver, TG and Xc are included in the composition of VLDL, enter the blood plasma and are transported to peripheral tissues. LDLs are formed from LDLs that are catabolized primarily through interaction with high affinity LDL receptors. Atorvastatin reduces the levels of Xc and lipoproteins in the blood plasma due to inhibition of HMG-CoA reductase and Xc synthesis in the liver, as well as by increasing the number of hepatic LDL receptors on the cell surface, which increases the uptake and catabolism of LDL. Atorvastatin reduces LDL production and the number of LDL particles. Atorvastatin causes a pronounced and persistent increase in the activity of LDL receptors in combination with favorable changes in the quality of circulating LDL particles. Lowers the level of LDL cholesterol in patients with homozygous hereditary hypercholesterolemia resistant to therapy with other lipid-lowering drugs. the level of total Xc (by 30-46%), Xc-LDL (by 41-61%), apolipoprotein B (by 34-50%) and TG (by 14-33%), simultaneously causing, to some extent, increasing levels Xc-HDL and apolipoprotein A. These results were similar in patients with heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia and mixed hyperlipidemia, including patients with non-insulin-dependent diabetes mellitus. Due to a decrease in the level of total Xc, Xc-LDL, in a non-insulin-dependent diabetes mellitus; -vascular diseases and, accordingly, reduces the risk of death.Studies of the effect of atorvastatin on cardiovascular morbidity and mortality have not yet been completed.; When using the drug in elderly patients, there were no differences in safety, efficacy or achievement of lipid-lowering therapy goals compared to the general population.
Pharmacokinetics
Absorption; After oral administration, atorvastatin is rapidly absorbed into the blood. Cmax in the blood plasma is reached within 1-2 hours. Eating a little reduces the speed and duration of the absorption of the drug (by 25% and 9%, respectively), however, cholesterol reduction is similar to that when taking atorvastatin without food. The absolute bioavailability of atorvastatin is approximately 12%, systemic bioavailability, which determines the inhibitory activity against HMG-CoA reductase, is 30%. Low systemic bioavailability is caused by presystemic metabolism in the gastrointestinal mucosa and during the "first pass" through the liver. Distribution; Atorvastatin's average Vd is approximately 381 l. Plasma protein binding - 98%; Metabolism; Atorvastatin is metabolized mainly in the liver with the participation of CYP3A4, CYP3A5 and CYP3A7 isoenzymes with the formation of pharmacologically active metabolites (ortho and parahydroxylated derivatives, beta-oxidation products). In vitro, ortho and parahydroxylated metabolites have 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.; Excretion; T1 / 2 - 14 h. Atorvastatin is excreted mainly in the bile after hepatic and / or extrahepatic metabolism. Inhibitory activity against HMG-CoA reductase remains for about 20-30 hours due to the presence of active metabolites. Less than 2% of the ingested dose of the drug is determined in the urine.; Pharmacokinetics in special clinical situations; Not excreted during hemodialysis. In women, Cmax is 20% higher, AUC - 10% lower. In patients with alcoholic cirrhosis, Cmax increases by 16 times, AUC - by 11 times.
Indications
- primary hypercholesterolemia, heterozygous familial and non-family hypercholesterolemia and combined (mixed) hyperlipidemia (Types IIa and IIb Fredrickson classification) in combination with lipid-lowering diet to reduce elevated levels of total Xc, Xc-LDL, apolipoprotein B, triglycerides and increasing Xc-HDL ; - increase in the serum TG level (type IV according to Fredrickson's classification),dysbetalipoproteinemia (type III according to Fredrickson's classification) with the ineffectiveness of diet therapy; - homozygous familial hypercholesterolemia - to reduce the levels of total Xc and Xc-LDL, when diet therapy and other non-pharmacological treatment methods are not sufficiently effective.
Contraindications
- active liver disease or increased activity of liver enzymes of unclear genesis (more than 3 times higher than VGN); - liver failure (classes A and B according to the Child-Pugh classification); - pregnancy; - lactation period; - age up to 18 years (efficacy and safety have not been established); - hypersensitivity to the drug.
Use during pregnancy and lactation
Atorvastatin is contraindicated for use during pregnancy and during breastfeeding. It is not known whether atorvastatin is excreted in breast milk. Given the possibility of adverse events in infants, if necessary, use of the drug during lactation should decide on the termination of breastfeeding. Women of reproductive age during treatment should use adequate contraceptives. Atorvastatin can be prescribed to women of reproductive age only if they have a very low probability of pregnancy and the patient is informed about the possible risk of treatment for the fetus.
Dosage and administration
The dose of the drug should be selected individually, taking into account the initial level of LDL-C, the goals of therapy and the patient's response to treatment. The drug can be taken at any time of the day 1 time / day, regardless of the meal.; The initial dose is 10 mg. The therapeutic dose varies from 10 mg to 80 mg / day. At the beginning and / or during the dose increase of Atorvatatin-Teva, it is necessary to monitor plasma lipid levels every 2-4 weeks and adjust the dose accordingly. Dose adjustment should be done at intervals of at least 4 weeks. The maximum daily dose is 80 mg. For patients with established CHD and other patients who are at high risk of cardiovascular complications, the following target lipid levels are recommended: X-LDL less than 3 mmol / l (or less than 115 mg / dL) and total X-y less than 5 mmol / l (or less than 190 mg / dl); in case of primary hypercholesterolemia and combined (mixed) hyperlipidemia in most patients, the necessary control of lipid levels is provided when taking the drug at a dose of 10 mg / day.A pronounced therapeutic effect is usually observed after 4 weeks and remains with long-term therapy. With heterozygous familial hypercholesterolemia, the initial dose is 10 mg / day. Carrying out individual dose adjustment every 4 weeks, you should bring it up to 40 mg / day. After that, you can increase the dose to a maximum level of 80 mg / day or use Atorvastatin-Teva at a dose of 40 mg in combination with bile acid sequestrants. With homozygous familial hypercholesterolemia, the drug is prescribed at a dose of 80 mg 1 time / day; For patients with renal failure dose adjustment is not required, since kidney disease does not affect plasma plasma levels of atorvastatin or the degree of lipid reduction when it is used. For liver failure, a dose reduction or drug withdrawal may be required.
Side effects
From the side of the central nervous system and peripheral nervous system: ≥1% - insomnia, headache, asthenic syndrome; <1% - malaise, dizziness, amnesia, paresthesia, peripheral neuropathy, hypoesthesia. On the part of the digestive system: ≥1% - nausea, diarrhea, abdominal pain, dyspepsia, flatulence, constipation (usually these phenomena weaken as treatment continues); <1% - vomiting, anorexia, hepatitis, pancreatitis, cholestatic jaundice. From the musculoskeletal system: ≥1% - myalgia; <1% - back pain, muscle cramps, myositis, myopathy, arthralgia, rhabdomyolysis; Allergic reactions: <1% - urticaria, pruritus, rash, anaphylaxis, bullous rash, polymorphic erythema exudative (including Stevens syndrome - Johnson's syndrome), Lyell's syndrome, angioedema; From the hematopoietic organs: <1% - thrombocytopenia; From the metabolic side: <1% - hypo- or hyperglycemia, increased serum CPK, peripheral edema, weight gain; Others: <1% - impotence, chest pain, secondary renal failure, alopecia , tinnitus, fatigue. During clinical studies, drug withdrawal due to side effects was required in less than 2% of patients.
Overdose
There is no specific antidote. In case of overdose, the necessary symptomatic and supportive therapy should be carried out. Monitoring of liver function and serum CK level is necessary. Hemodialysis is ineffective.
Interaction with other drugs
The risk of myopathy in the treatment of HMG-CoA reductase inhibitors increases when they are used in combination with cyclosporine, fibrates, macrolide antibiotics (including erythromycin), azole antifungal agents or nicotinic acid. In some rare cases, these combinations cause rhabdomyolysis, accompanied by renal failure, due to myoglobinuria. In this regard, a careful assessment of the risk-benefit ratio of the combined treatment is necessary. Atorvastatin metabolism is performed with the participation of the CYP3A4 isoenzyme. When using atorvastatin in combination with CYP3A4 isoenzyme inhibitors (for example, cyclosporine, macrolide antibiotics, for example, erythromycin and clarithromycin, nefazodone, azole antifungal drugs, for example, itraconazole, and HIV protease inhibitors), it is possible to increase atorvastatin concentration in an area of an inaccuracytomatin in an inaccuracytomatin in an inaccuracytomatin in an inaccuracytomatin level in an inaccuracytocin in an inaccuracytomatin plasma profile. interactions. In this regard, particular caution should be exercised in the appointment of atorvastatin in combination with the above drugs. Simultaneous use with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone) increases the risk of reducing the level of endogenous steroid hormones (caution is required for these combinations); Atorvastatin and its metabolites are substrates for P-glycoprotein. P-glycoprotein inhibitors (for example, cyclosporine) can increase the bioavailability of atorvastatin. With the simultaneous use of atorvastatin and erythromycin (500 mg 4 times / day) or clarithromycin (500 mg 2 times / day), which inhibit the isoenzyme CYP3A4, an increase in atorvastatin concentration was observed blood plasma. With the simultaneous use of atorvastatin (10 mg 1 time / day) and azithromycin (500 mg 1 time / day), the plasma concentration of atorvastatin did not change.; With the combined use of atorvastatin at a dose of 40 mg and itraconazole at a dose of 200 mg 1a day / day there was an increase in AUC to a value that was 3 times greater than monotherapy.; Simultaneous use of atorvastatin with protease inhibitors that are inhibitors of the CYP3A4 isoenzyme was accompanied by an increase in plasma concentration of atorvastatin.; Effects of drugs that induce the CYP3A4 isoenzyme (for example, rifampicin and phenazone), on atorvastatin unknown.Interaction with atorvastatin and other substrates of this isoenzyme is unknown, but the possibility of such interaction should be considered when using drugs with a low therapeutic index, in particular, class III antiarrhythmic drugs, for example, amiodarone. The risk of atorvastatin myopathy may increase with concomitant use of fibrates. In vitro studies suggest that gemfibrozil may also interact with atorvastatin by inhibiting its glucuronidation, which may cause an increase in plasma atorvastatin concentrations. When re-taking digoxin and atorvastatin at a dose of 10 mg, the equilibrium concentration of digoxin in the blood plasma did not change. However, when using digoxin in combination with atorvastatin at a dose of 80 mg / day, the concentration of digoxin increased by about 20%. Patients receiving digoxin in combination with atorvastatin should be monitored. The use of atorvastatin in combination with an oral contraceptive containing norethisterone and ethinyl estradiol caused an increase in plasma concentrations of norethisterone and ethinyl estradiol. These increases in concentration should be considered when choosing doses of oral contraceptives. With simultaneous use of atorvastatin and a oral contraceptive containing norethisterone and ethinyl estradiol, there was a significant increase in the AUC of norethisterone and ethinyl estradiol by about 30% and 20%, respectively. This effect should be taken into account when choosing an oral contraceptive for a woman receiving atorvastatin.; When colestipol was given in combination with atorvastatin, plasma levels of atorvastatin decreased by about 25%. However, with the combined use of atorvastatin and colestipol, the effect on lipids was more pronounced than when using each of these drugs separately. When co-administered atorvastatin and a suspension containing magnesium and aluminum hydroxide, the concentration of atorvastatin in plasma decreased by about 35%; however, the degree of reduction in the level of LDL did not change. While taking atorvastatin in combination with warfarin, there was a slight decrease in prothrombin time in the first days of atorvastatin; however, the prothrombin time returned to normal in the next 15 days.However, in the case of co-administration of atorvastatin and warfarin, patients should be carefully monitored. With simultaneous use of atorvastatin does not affect the pharmacokinetics of phenazone, therefore, interaction with other drugs metabolized by the same cytochrome isoenzymes is not expected. significant interaction between these drugs.; When combined administration of atorvastatin at a dose of 80 mg and amlodipine at a dose of 10 mg changes pharmacokinetic x atorvastatin parameters was not detected in the equilibrium state;. There were no clinically significant undesirable reaction of atorvastatin and antihypertensive agents. Studies of interaction with all specific drugs have not been conducted.; Atorvastatin did not have a clinically significant effect on the concentration of terfenadine in the blood plasma, which is metabolized mainly by the CYP3A4 isoenzyme; therefore, it is unlikely that atorvastatin can significantly affect the pharmacokinetic parameters of other CYP3A4 isoenzyme substrates.; Grapefruit juice contains at least one ingredient that is a CYP3A4 inhibitor, and may cause an increase in the plasma concentration of those drugs that are metabolized by CYP3A4. With a daily intake of 240 ml of grapefruit juice, an increase in the AUC of atorvastatin by 37% and a decrease in the AUC of the active orthohydroxy metabolite was observed by 20.4%. When a large amount of grapefruit juice was consumed (more than 1.2 liters per day for 5 days), the AUC value of atorvastatin increased 2.5 times, and the AUC value of active HMG-CoA reductase inhibitors (atorvastatin and its metabolites) increased 1.3 times. In this regard, the consumption of large quantities of grapefruit juice during treatment with atorvastatin is not recommended.
special instructions
Before starting therapy with Atorvastatin-Tev, the patient should be prescribed a standard hypocholesterol diet, which he must follow during the entire period of treatment. The use of HMG-CoA reductase inhibitors to lower blood lipids may lead to changes in biochemical parameters reflecting liver function. Liver function should be monitored before starting therapy, 6 weeks, 12 weeks after starting atorvastatin and after each dose increase, as well as periodically, for example, every 6 months. An increase in liver enzyme activity in the serum may be observed during therapy with atorvastatin.Patients who have increased levels of enzymes should be monitored until the level of enzymes returns to normal. In the case of a persistent increase in ALT or ACT to a level exceeding more than 3 times the VGN, it is recommended to reduce the dose of Atorvastatin-Teva or discontinue treatment. Atorvastatin-Teva should be used with caution in patients who abuse alcohol and / or have liver disease. Active liver disease or a persistent increase in the activity of aminotransferases of unclear genesis serve as contraindications to the administration of Atorvastatin-Tev. Treatment with atorvastatin, like other HMG-CoA reductase inhibitors, can cause myopathy. The diagnosis of myopathy (pain and weakness in the muscles in combination with an increase in CPK more than 10 times compared with VGN) should be discussed in patients with common myalgias or muscle weakness and / or a pronounced increase in the activity of CPK. Patients should be warned that they should immediately inform the doctor about the appearance of unexplained pain or weakness in the muscles, if they are accompanied by indisposition or fever. Atorvastatin therapy should be discontinued in case of a pronounced increase in CPK activity or in the presence of confirmed or suspected myopathy. The risk of myopathy in the treatment of other drugs of this class increased with the simultaneous use of cyclosporine, fibrates, erythromycin, nicotinic acid or azole antifungal agents. Many of these drugs inhibit the metabolism mediated by the CYP3A4 isoenzyme and / or the transport of drugs. Atorvastatin is biotransformed by CYP3A4. When prescribing atorvastatin in combination with fibrates, erythromycin, immunosuppressive drugs, azole antifungal agents, or nicotinic acid in hypolipidemic doses, you should carefully evaluate the risk and the expected benefit of treatment and regularly monitor patients for pain, to look for pain, to look for pain, to look for pain, to find pain. especially during the first months of treatment and during periods of increasing the dose of any drug. In such situations, periodic determination of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy. When using atorvastatin, like other drugs of this class,cases of rhabdomyolysis with acute renal failure caused by myoglobinuria are described. Atorvastatin therapy should be temporarily stopped or completely canceled if there are signs of possible myopathy or a risk factor for the development of renal failure in the presence of rhabdomyolysis (for example, severe acute infection, hypotension, serious surgery, trauma, severe metabolic, endocrine and electrolyte disturbances and uncontrolled seizures) .; Before starting therapy with Atorvastatin-Teva To control hypercholesterolemia through adequate diet therapy, increasing physical activity, reducing body weight in patients with obesity and treating other conditions. The effect on the ability to drive motor vehicles and control mechanisms; The adverse effects of atorvastatin on the ability to drive and work with mechanisms were not reported.