Index of drugs

Hypercholesterolemia. The drug is indicated for use at the same time as the recommended diet, in order to lower the increased total cholesterol, LDL cholesterol (LDL-C), apolipoprotein B or triglycerides in adults, adolescents and children aged 10 years or older with primary hypercholesterolemia, heterozygous familial hypercholesterolemia. or mixed hyperlipidemia (such as type II and type II b by Frederickson), when the response to diet and other non-pharmacological treatments is inappropriate. The drug is also indicated for the reduction of total and LDL cholesterol in adult patients with familial homozygous hypercholesterolemia, in addition to other lipid-lowering treatments (eg LDL apheresis) or if such treatments are not available.Prevention of cardiovascular diseases. Prevention of cardiovascular events in adult patients at risk for the first cardiovascular event being assessed as large, in addition to correcting other risk factors.

1 tabl powl. contains 10 mg, 20 mg or 40 mg of Atorvastatin in the form of a Calcium salt. The preparation contains lactose.

A selective, competitive inhibitor of HMG-CoA reductase, an enzyme responsible for the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Atorvastatin reduces the concentration of cholesterol and serum lipoproteins by inhibiting HMG-CoA reductase activity, which in turn reduces the synthesis of cholesterol in the liver. Atorvastatin increases the number of LDL receptors on the surface of the hepatocytes cell membrane, thus increasing the uptake and catabolism of LDL. It reduces the production of LDL and the number of LDL molecules, causes an intensified and sustained increase in LDL receptor activity and preferably changes the quality of circulating LDL molecules. Decreases LDL-cholesterol in patients with homozygous familial hypercholesterolaemia who do not usually respond to treatment with lipid-lowering preparations. Atorvastatin reduces total cholesterol (30-46%), LDL-cholesterol (41-61%), apolipoprotein B (34-50%) and triglycerides (14-33%) and increases HDL-cholesterol and apolipoprotein A1. It has been proven that lowering total cholesterol, LDL cholesterol and apolipoprotein B reduces the risk of cardiovascular events and cardiovascular deaths. Following oral administration, atorvastatin is rapidly absorbed, reaching peak plasma concentrations within 1-2 hours. Absolute bioavailability is approximately 12%, and the systemic availability of the active HMG-CoA reductase inhibitor is approximately 30%. Plasma proteins are ≥ 98%. It is metabolized in the liver by cytochrome P-450 3A4 to ortho- and parahydroxylated derivatives and various beta-oxidation products. About 70% of the HMG-CoA reductase inhibitory activity in the blood is attributed to active metabolites. It is excreted mainly in the bile. Medium T_0,5 in the elimination phase, it is about 14 hours. T_0,5 HMG-CoA reductase inhibitory activity is approx. 20-30 h, due to the interaction of active metabolites. Renal failure does not affect the concentration of atorvastatin and its active metabolites in the blood, nor its effectiveness. The concentration of atorvastatin and its active metabolites in the blood is significantly increased (C_max approximately 16 times and AUC approximately 11 times) in patients with chronic alcohol-related liver injury (Child-Pugh B).

Hypersensitivity to atorvastatin or any of the excipients. Active liver disease or persistent, unexplained increase in serum transaminases (3 times the upper limit of values ​​considered normal). Pregnancy and breastfeeding. Women of childbearing potential who do not use adequate contraceptives.

Liver function tests should be performed prior to treatment initiation and then periodically during treatment.Liver function tests should be performed in patients who develop any signs or symptoms indicative of liver damage. Patients who increase transaminase levels should be monitored until these abnormalities resolve. If transaminase elevation greater than 3-fold GGN persists, a dose reduction or discontinuation of atorvastatin therapy is recommended. The drug should be used with caution in patients who consume significant amounts of alcohol and / or in patients with a history of liver disease. In patients without ischemic heart disease who had recently had a stroke or transient ischemic attack (TIA), the incidence of haemorrhagic stroke was higher in patients who started taking atorvastatin 80 mg than in patients who received placebo. An increased risk was found especially in patients who had had a hemorrhagic stroke or lacunar infarction (stroke) prior to the study. In patients with pre-existing hemorrhagic stroke or lacunar infarct, the risk-benefit ratio is not specified, and the potential risk of a hemorrhagic stroke should be carefully considered prior to treatment initiation. Atorvastatin should be prescribed cautiously to patients with factors predisposing to rhabdomyolysis; before initiating statin therapy, creatine kinase (CK) activity should be determined in the following situations: renal dysfunction; Hypothyroidism; hereditary muscular or medical history disorders; muscle toxicity during prior treatment with a statin or fibrate history; liver disease and / or heavy alcohol intake; in elderly patients (> 70 years), the need for such tests should be considered depending on the presence of other risk factors predisposing to rhabdomyolysis; cases in which an increase in CK activity may occur (eg, interactions and patients with a polymorphism in the OATP1B1 encoding gene - in these patients, the exposure to atorvastatin may be increased 2.4-fold). In these situations, the risks associated with the treatment should be carefully considered in relation to the possible benefits, and clinical observation is recommended. Do not start treatment if CK activity is significantly increased (> 5 times ULN). Treatment with atorvastatin must be discontinued if CK activity increases clinically (> 10 times ULN) or if rhabdomyolysis is diagnosed or suspected. If muscle symptoms occur during treatment (muscle pain, muscle spasms or weakness, especially if these symptoms are accompanied by malaise and fever) and if the CK level is significantly increased (> 5 times ULN), treatment should be discontinued. If the muscle symptoms are severe and cause discomfort every day, discontinuation of treatment should be considered even if the CK elevation is ≤ 5 times ULN. If the symptoms subside and CK activity returns to normal, re-introduction of atorvastatin or another statin may be considered at the lowest dose and under strict control. The risk of rhabdomyolysis increases when atorvastatin is co-administered with drugs that increase its plasma concentration, e.g. strong CYP3A4 inhibitors or protein transporters (eg cyclosporin, telithromycin, Clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, Itraconazole, posaconazole, inhibitors) HIV proteases, including ritonavir, lopinavir, atazanavir, indinavir, darunavir and the like). The risk of myopathy is also increased when concomitant use of atorvastatin and gemfibrozil and other derivatives of fibrin, Erythromycin, niacin and ezetimibe. If possible, alternative treatment should be considered. If the administration of these drugs and atorvastatin is necessary, the benefits and risks of treatment should be carefully considered. It is recommended that patients receive a lower dose of maximum atorvastatin when co-administered with drugs that increase plasma concentrations of atorvastatin; in the case of strong CYP3A4 inhibitors, a lower initial dose should be considered and appropriate monitoring of patients is recommended. Co-administration of atorvastatin and fusidic acid is not recommended. If there is a suspicion that the patient develops interstitial lung disease, statin therapy should be discontinued.Statins cause an increase in blood Glucose levels and in some patients at high risk of developing diabetes in the future, may lead to hyperglycaemia to the extent that it is appropriate to implement the official course of action in diabetic patients. However, the benefits of reducing the vascular risk after using statins outweigh the risk of developing diabetes and therefore this risk should not be a reason for stopping statin treatment. In patients with risk factors (fasting glucose 5.6-6.9 mmol / l, BMI> 30 kg / m², increased triglycerides, hypertension), clinical status and biochemical parameters should be monitored according to national guidelines. Data on the use of the product in children aged 6-10 years are limited - atorvastatin is not indicated for use in children under the age of 10 years. In patients aged 10 years or older, data on the safety of a dose greater than 20 mg (about 0.5 mg / kg) are limited. There are no developmental studies of the preparation regarding safety in the pediatric population. The product contains lactose - should not be used in patients with rare hereditary problems of lactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose.

Administration of the preparation during pregnancy and breast-feeding is contraindicated. Women of childbearing age should use effective methods of contraception.

Common: rhinitis, allergic reactions, hyperglycemia, headache, sore throat and larynx, nosebleeds, constipation, flatulence, dyspepsia, nausea, diarrhea, muscle pain, joint pain, limb pain, muscle cramps , swollen joints, back pain, abnormal liver function tests, increased creatine kinase activity. Uncommon: thrombocytopenia, hypoglycaemia, weight gain, anorexia, nightmares, insomnia, dizziness, paresthesia, hyposthesia, taste disturbances, amnesia, blurred vision, tinnitus, vomiting, epigastric and abdominal pain, belching, pancreatitis, alopecia , hepatitis, urticaria, skin rash, pruritus, neck pain, fatigability of the muscles, malaise, fatigue, chest pain, peripheral edema, weakness, fever, presence of white blood cells in the urine. Rare: peripheral neuropathy, visual impairment, congestive jaundice, angioneurotic edema, bladder rash including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, myopathy, myositis, rhabdomyolysis, tendinopathy sometimes complicated by tendon rupture. Very rare: anaphylaxis, hearing loss, liver failure, gynecomastia. During the use of Atorvastatin, an increase in serum transaminases was observed (these changes were usually mild and transient and did not require discontinuation of therapy). Clinically significant (more than 3-fold GGN) elevations of blood transaminases occurred in 0.8% of patients (it was dose-dependent and transient in all patients). Increased CK activity in the blood (more than 3 times above ULN) was noted in 2.5% of patients. A 10-fold increase in CK activity occurred in 0.4% of patients. The following side effects have been reported with some statins: sexual dysfunction, depression, individual cases of interstitial lung disease (especially during long-term treatment), diabetes (frequency depends on the presence or absence of risk factors: fasting blood glucose ≥5,6 mmol / l, BMI> 30 kg / m², increased triglyceride levels, a history of hypertension).Children. Common: headache, abdominal pain, alanine aminotransferase increase, increase in creatine phosphokinase in the blood. Based on the available data, it can be expected that the frequency, type and severity of side effects in children will be similar to that in adult patients. Data on long-term safety in children are limited.

Orally. The dose should be determined individually depending on the initial LDL cholesterol concentration, the therapeutic target, and the patient's response. The usual starting dose is 10 mg once a day. The dose should be adjusted at intervals of 4 weeks or longer. The maximum dose is 80 mg once a day.Primary hypercholesterolemia and complex (mixed) hyperlipidemia: in most patients, the control of the disease is obtained with a dose of 10 mg per day. Therapeutic response is evident within 2 weeks of treatment, and the maximum therapeutic response is usually achieved within 4 weeks.Heterozygous familial hypercholesterolaemia: the starting dose is 10 mg per day. Doses should be determined individually for each patient and adjusted every 4 weeks to 40 mg daily. You can then either increase the dose to a maximum of 80 mg daily, or use a bile acid sequestrant in combination with a 40 mg dose of atorvastatin once a day.Homozygous familial hypercholesterolaemia: doses are 10-80 mg per day. In these patients, atorvastatin should be used as a supplement to other lipid-lowering therapy (eg LDL apheresis) or if such treatment is not available.Prevention of cardiovascular diseases: 10 mg daily. Higher doses may be necessary to obtain (LDL) cholesterol levels that are consistent with current guidelines. No dose adjustment is required in patients with renal impairment or in elderly patients.Children and youth. Hypercholesterolemia: treatment only under the supervision of a doctor with experience in the treatment of the pediatric population, and patients should be regularly evaluated to assess the progress of treatment. For patients aged 10 years and over, the recommended starting dose of atorvastatin is 10 mg daily and may be increased gradually to 20 mg daily. The dose should be increased depending on the individual response and tolerance of the patient. Safety data for children and adolescents treated with doses higher than 20 mg, equivalent to approximately 0.5 mg / kg are limited. Atorvastatin is not indicated for the treatment of patients under 10 years of age - other pharmaceutical forms and / or other strengths of the preparation may be appropriate for this population.
The preparation can be taken at any time of the day, regardless of meals.