Atorvastatin 20 mg
Lipid-lowering agent from the group of statins. Selective competitive inhibitor of HMG-CoA reductase - an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonic acid, which is a precursor of sterols, including cholesterol. Triglycerides (TG) and cholesterol in the liver are included in very low-density lipoproteins (VLDL), enter the blood plasma and are transported to peripheral tissues. Low density lipoproteins (LDL) are formed from VLDL during interaction with LDL receptors. Atorvastatin lowers plasma cholesterol and lipoprotein concentrations by inhibiting HMG-CoA reductase, synthesis of cholesterol in the liver, and increasing the number of “liver” LDL receptors on the cell surface, which leads to increased uptake and LDL catabolism. Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces the concentration of LDL in patients with homozygous seminal hypercholesterolemia, which usually does not respond to therapy with lipid-lowering drugs. Reduces the concentration of total cholesterol by 30-46%, LDL - by 41-61%, apolipoprotein B - by 34-50% and TG - by 14-33%; causes an increase in the concentration of cholesterol-HDL (high density lipoprotein) and apolipoprotein A. Dose-dependently decreases the concentration of LDL in patients with homozygous hereditary hypercholesterolemia resistant to therapy with other hypolipidemic agents.
Absorption is high. Cmax in blood plasma is achieved in 1-2 hours, Cmax in women is 20% higher, AUC - 10% lower; In liver failure in patients with alcoholic cirrhosis of the liver (Child-Pugh B scale), Cmax and AUC increase 16 and 11 times, respectively. Food somewhat reduces the rate and duration of absorption of the drug (by 25% and 9%, respectively), but lowering LDL cholesterol is similar to that when using Atorvastatin without food. Atorvastatin concentration when applied in the evening is lower than in the morning (approximately 30%). A linear relationship was found between the degree of absorption and the dose of the drug. Bioavailability - 12%, systemic inaccessibility of inhibitory activity against HMG-CoA reductase - 30%.Low systemic bioavailability due to presystemic metabolism in the mucous membrane of the gastrointestinal tract and the "first pass" through the liver. Vd - 381 l, connection with plasma proteins - 98%. It is metabolized mainly in the liver under the action of CYP3A4 isoenzyme with the formation of pharmacologically active metabolites (ortho and parahydroxylated derivatives, beta-oxidation products). In vitro ortho- and para-hydroxylated 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. It is excreted with bile after hepatic and / or extrahepatic metabolism (it does not undergo a pronounced enterohepatic recirculation). T1 / 2 - 14 h. The inhibitory activity on HMG-CoA reductase remains about 20-30 h due to the presence of active metabolites. Less than 2% of the ingested dose of the drug is determined in the urine. Not displayed during hemodialysis.
- in conjunction with a diet to reduce elevated total cholesterol concentrations, cholesterol / LDL, apolipoprotein B and triglyceride levels, and increasing the concentration of HDL cholesterol in patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolemia and combined (mixed) hyperlipidemia (Types IIa and IIb according to Fredrickson) ; - in combination with a diet for the treatment of patients with elevated serum concentrations of triglycerides (type IV according to Fredrickson) and patients with dysbetalipoproteinemia (type III according to Fredrickson), in whom diet therapy will not give an adequate effect; - to reduce the concentration of total cholesterol and cholesterol / LDL in patients with homozygous familial hypercholesterolemia, when diet therapy and other non-pharmacological treatment methods are not sufficiently effective.
- hypersensitivity to the drug; - active liver disease or increased activity of "liver" enzymes of unknown origin (more than 3 times compared with the upper limit of normal); liver failure (severity on a Child-Pugh A and B scale); - pregnancy; - lactation period; - women of reproductive age who do not use adequate methods of contraception; - age up to 18 years (efficacy and safety have not been established).With caution: alcohol abuse, a history of liver disease, severe electrolyte imbalance, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical procedures, injuries, skeletal muscle diseases
Use during pregnancy and lactation
Atorvastatin is contraindicated for use during pregnancy and lactation (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 methods of contraception. Atorvastatin can be used in women of reproductive age only if the probability of pregnancy is very low and the patient is informed about the possible risk of treatment for the fetus.
Dosage and administration
Before using Atorvastatin, the patient should be advised to recommend a standard lipid-lowering diet, which he must continue to follow throughout the entire period of therapy. The initial dose is an average of 10 mg 1 time / day. The dose varies from 10 to 80 mg 1 time / day. The drug can be taken at any time of the day with food or regardless of meal times. The dose is selected based on the initial concentrations of cholesterol / LDL, the goal of therapy and individual effect. At the beginning of treatment and / or during the dose increase of atorvastatin, it is necessary every 2-4 weeks to control the concentration of lipids in the blood plasma and correct the dose accordingly. Primary hypercholesterolemia and mixed hyperlipidemia. as well as type III and IV according to Fredrickson. In most cases, it is enough to use a dose of 10 mg of the drug Atorvastatin 1 time per day. A significant therapeutic effect is observed after 2 weeks, as a rule, and the maximum therapeutic effect is usually observed after 4 weeks. With long-term treatment, this effect persists. Homozygous familial hypercholesterolemia. Apply at a dose of 80 mg (4 pills of 20 mg) 1 time per day. The use of the drug in patients with renal insufficiency and kidney disease does not affect the level of atorvastatin in the blood plasma or the degree of cholesterol / LDL cholesterol reduction when it is used, therefore, changing the dose of the drug is not required. In case of hepatic insufficiency, the dose must be reduced.When using the drug in elderly patients, there were no differences in safety, efficacy, or achievement of lipid-lowering therapy goals in comparison with the general population.
On the part of the nervous system: most often 2% - insomnia, dizziness; less than 2% - headache, asthenia, malaise, drowsiness, nightmares, paresthesias, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesis, migraine, depression, hypoesthesia, loss of consciousness. On the part of the sense organs: less often 2% - amblyopia, tinnitus, dry conjunctiva, disturbed accommodation, hemorrhage into the retina, blindness, glaucoma, paroemia, loss of taste, taste perversion. Since the cardiovascular system: usually 2% - chest pain; less than 2% - feeling of palpitations, symptoms of vasodilation, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris. From the hematopoietic system: less often 2% - anemia, lymphadenopathy, thrombocytopenia. On the part of the respiratory system: more often 2% - bronchitis, rhinitis; less often 2% - pneumonia, dyspnea, exacerbation of bronchial asthma, nosebleeds. On the part of the digestive system: more often 2% - nausea; less than 2% - heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, decreased or increased appetite, dry oral mucosa, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, abnormal liver function, rectal bleeding, melena, bleeding gums, tenesmus. From the musculoskeletal system: most often 2% - arthritis; less than 2% - leg muscle cramps, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonia, contractures of the joints. From the genitourinary system: more often 2% - urogenital infections, peripheral edema; less than 2% - dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, imperative urination to urinate), nephritis, hematuria, vaginal bleeding, nephrurolithiasis, metrorrhagia, epididymitis, decrease in blood pressure, impotence, nephrorolithiasis, metrorrhagia, epididymitis, decreased blood pressure, impotence, nephrorolithiasis, metrorrhagia, epididymitis, decreased blood pressure, impotence, nephrorolithiasis, metrorrhagia, epididymitis, decreased blood pressure, impotence, nephrorolithiasis; failure. On the part of the skin: usually 2% - alopecia, xeroderma, increased sweating, eczema, seborrhea, ecchymosis, petechiae.Allergic reactions: less than 2% - pruritus, rash, contact dermatitis, rarely - urticaria, angioedema, facial edema, photosensitization, anaphylaxis, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrosis ( ). Laboratory indicators: less often 2% - hyperglycemia, hypoglycemia, increased serum CPK activity, albuminuria. Others: less than 2% - weight gain, gynecomastia, mastodynia, exacerbation of the course of gout.
Treatment: there is no specific antidote, symptomatic therapy is carried out. Hemodialysis is ineffective.
Interaction with other drugs
The risk of myopathy during treatment with other drugs of this class is increased with simultaneous use of cyclosporine, fibrates, erythromycin, clarithromycin, immunosuppressive, antifungal agents related to azoles, and nicotinic acid in lipid-lowering doses. With simultaneous use of atorvastatin by mouth and a suspension containing magnesium and aluminum hydroxide, plasma concentrations of atorvastatin decreased by approximately 35%, however, the degree of decrease in the concentration of cholesterol / LDL did not change. With simultaneous use, atorvastatin does not affect the pharmacokinetics of phenazone (antipyrine), therefore interaction with other drugs metabolized by the same cytochrome CYPZA4 isoenzymes is not expected. With simultaneous use of colestipol, the concentration of atorvastatin in the blood plasma decreased by approximately 25%. However, the lipid-lowering effect of the combination of atorvastatin and colestipol was superior to that of each drug separately. With repeated use of 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. With simultaneous use of atorvastatin and erythromycin (500 mg 4 times / day) or clarithromycin (500 mg 2 times / day), which inhibit CYPZA4 isoenzyme, an increase in plasma concentration of atorvastatin was observed.With simultaneous use of atorvastatin (10 mg 1 time / day) and azithromycin (500 mg 1 time / day), the concentration of atorvastatin in the blood plasma did not change. Atorvastatin did not have a clinically significant effect on the concentration of terfenadine in the blood plasma, which is metabolized mainly by CYPZA4 isoenzyme; in this regard, it is unlikely that atorvastatin can significantly affect the pharmacokinetic parameters of other substrates of CYPZA4 isoenzyme. With simultaneous use of atorvastatin and a oral contraceptive containing norethisterone and ethinyl estradiol, there was a significant increase in the AUC of norethindrone and ethinyl estradiol by about 30% and 20% respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving atorvastatin. Simultaneous use with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone) increases the risk of reducing endogenous steroid hormones (caution should be exercised). When studying the interaction of atorvastatin with warfarin and cimetidine, there are no signs of a clinically significant interaction. With simultaneous use of atorvastatin 80 mg and amlodipine 10 mg, the pharmacokinetics of atorvastatin did not change in equilibrium. No clinically significant undesirable interaction of atorvastatin and antihypertensive drugs. The simultaneous use of atorvastatin with protease inhibitors, known as inhibitors of coenzyme CYPZA4, was accompanied by an increase in plasma concentrations of atorvastatin. Pharmaceutical incompatibility is not known.
Before starting therapy with Atorvastatin, 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 reduce the concentration of lipids in the blood can lead to changes in biochemical parameters reflecting the function of the liver. Liver function should be monitored before starting therapy, 6 weeks, 12 weeks after starting to use atorvastatin and after each dose increase, as well as periodically, for example, every 6 months.An increase in the activity of liver enzymes in the serum can be observed during therapy with atorvastatin. Patients who have increased activity of enzymes should be under control until the activity of enzymes returns to normal. If the values of alanine aminotransferase (ALT) or aspartate aminotransferase (ACT) are more than 3 times higher than the upper tolerance limit, it is recommended to reduce the dose of Atorvastatin or discontinue treatment. Atorvastatin 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 “liver” transaminases of unknown origin are contraindications to the use of atorvastatin. Treatment with atorvastatin can cause myopathy. The diagnosis of myopathy (pain and weakness in the muscles in combination with an increase in the activity of CPK more than 10 times compared with the upper limit of normal) should be in patients with common myalgias, muscle soreness or 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 the event of a pronounced increase in CPK activity or in the presence of confirmed or suspected myopathy. The risk of myopathy during treatment with other drugs of this class increases with simultaneous use with cyclosporine, fibrates, erythromycin, clarithromycin, immunosuppressive, antifungal agents related to azoles, and nicotinic acid in lipid-lowering doses. Many of these drugs inhibit the metabolism mediated by the CYP3 A4 isoenzyme, and / or the transport of drugs. Atorvastatin is biotransformed by the CYP3A4 isoenzyme. Using atorvastatin at the same time as fibrates, erythromycin, immunosuppressants, azole antifungals or nicotinic acid in lipid-lowering doses, you should carefully weigh the expected benefits and risks of treatment and regularly monitor patients to identify pain or weakness in muscles, especially during the first months of treatment and a period 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, as well as other drugs of this class, cases of rhabdomyolysis with acute renal failure caused by myoglobinuria are described. Atorvastatin therapy should be temporarily discontinued or completely discontinued if there is evidence of possible myopathy or a risk factor for the development of renal failure in the presence of rhabdomyolysis (for example, severe acute infection, hypotension, extensive surgical surgery, trauma, severe metabolic, endocrine and electrolyte disturbances and uncontrolled disorders ). Before starting treatment with atorvastatin, it is necessary to try to control hypercholesterolemia by adequate diet therapy, increasing physical activity, reducing body weight in patients with obesity and treating other conditions. There are reports of the development of atonic fasciitis on the background of the use of Atorvastatin, however, the connection with the administration of the drug is possible, but so far not proven, the etiology is unknown. Influence on the ability to drive vehicles and work with mechanisms. No adverse effect of Atorvastatin on the ability to drive and work with mechanisms was reported.