Index of drugs

hypercholesterolemia: supplementation of dietary therapy in order to lower elevated total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides in adults, adolescents and children aged 10 years or older with primary hypercholesterolaemia, including heterozygous familial hypercholesterolaemia, or complex (mixed) hyperlipidemia (corresponding to hyperlipidemia) type IIa and IIb according to Fredrickson's classification) in the case of insufficient response to the use of diet and other non-pharmacological methods of treatment. The drug is also used to lower total cholesterol and LDL-cholesterol in adults with a homozygous form of familial hypercholesterolemia as a therapy added to other lipid-lowering therapy (eg LDL cholesterol apheresis) or when such therapy is not available.Prevention of cardiovascular eventsin patients who are at high risk for the first cardiovascular event, along with measures to reduce other risk factors.

1 tabl powl. contains 10 mg, 20 mg, 40 mg or 80 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 cholesterol synthesis in the liver and leads to an increase in the number of LDL receptors on the surface of the hepatocytes cell membrane, thereby 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 have not usually responded to lipid-lowering therapy. 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 mortality. After oral administration, atorvastatin is rapidly absorbed, reaching a maximum blood concentration after 1-2 h. The absolute bioavailability is about 12% and the systemic HMG-CoA reductase inhibitory activity is about 30%. Plasma proteins bind at least 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 in bile. T_0,5 is about 14 hours. T_0,5 HMG-CoA reductase inhibitory activity is 20-30 h, due to the effect 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 the active substance or to any of the excipients. Active liver disease or unexplained, permanently elevated blood aminotransferase levels exceeding the upper limit of 3 times the normal range. Pregnancy. Breastfeeding period. Women of childbearing potential not using effective methods of contraception.

Caution should be exercised when administering the drug to patients who consume significant amounts of alcohol and / or liver disease. Patients who develop signs or symptoms of liver damage should undergo liver function tests. If transaminase elevation is detected, the patient should be monitored until resolution of the disorder.In the case of persistent elevation of aminotransferases, greater than 3 times the upper limit of normal, a dose reduction or discontinuation is recommended. In patients without history of ischemic heart disease who have recently suffered a cerebrovascular accident or TIA episode (transient ischemic attack), haemorrhagic attacks have been more frequent in patients treated with atorvastatin 80 mg compared with the placebo group. The increase in risk was particularly noticeable in patients with a history of hemorrhagic stroke or a history of lacunar infarction - in these patients, the risk-benefit ratio of atorvastatin 80 mg is unequivocal; in such cases, the potential risk of haemorrhagic stroke should be carefully considered before starting treatment. Caution should be exercised in patients with predisposing factors for rhabdomyolysis: renal dysfunction, hypothyroidism, muscle disease or hereditary history of muscle disease, muscle damage associated with prior use of statins or fibrates, and history of liver disease ( or) in patients consuming large amounts of alcohol, in elderly patients (> 70 years) and in situations where the plasma drug concentration may be increased (eg, interactions and patients with polymorphism in the OATP1B1 encoding gene - in these patients exposure to atorvastatin it can be increased 2.4 times). In these groups of patients, creatine kinase (CK) should be measured before starting treatment - if the CK activity is higher than 5 times the upper limit of normal (ULN), treatment should not be started. In these groups of patients, the expected benefits of treatment and the associated risks should be considered before starting treatment, and clinical symptoms should also be monitored. Drug administration must be discontinued if CK levels increase (> 10 times ULN) or if rhabdomyolysis occurs or is suspected, and if there are muscle symptoms (muscle pain, spasm or muscle weakness, especially if it is generally poor) well-being or fever) and increased CK activity above 5-fold GGN; if the muscle symptoms are severe and cause discomfort on a daily basis, discontinuation of treatment should be considered even if the CK activity is less than 5 times ULN. If clinical symptoms resolve and CK activity returns to normal, re-inclusion of atorvastatin or another statin at the lowest dose and with close clinical monitoring may be considered. The risk of rhabdomyolysis increases with the concomitant use of drugs that may increase plasma concentrations of atorvastatin such as strong CYP3A4 inhibitors or transporter inhibitors (eg cyclosporin, telithromycin, Clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, Itraconazole, posaconazole, HIV protease inhibitors). The risk of myopathy may also be increased when concomitant use of gemfibrozil and other derivatives of fibrin, Erythromycin, niacin and ezetimibe. Whenever possible, alternative medicines should be considered. In cases where the combination of these medicines with atorvastatin is required, the benefits and risks of treatment should be carefully considered. If a patient is on medication to increase plasma concentrations of Atorvastatin, a lower dose of atorvastatin is recommended. For strong CYP3A4 inhibitors, a lower initial dose of atorvastatin should be considered and appropriate clinical observation is recommended. Co-administration of atorvastatin and fusidic acid is not recommended. If you suspect interstitial lung disease, statin therapy should be discontinued. The available data suggest that statins increase Glucose levels and in some patients at high risk of future diabetes may cause hyperglycaemia requiring medical control typical of people with diabetes. The benefits of reducing vascular risk by using statins outweigh the above-described risk of hyperglycaemia, so this risk should not be a reason for stopping statin therapy. Patients at risk (patients with fasting glucose 5,6 to 6,9 mmol / l, BMI> 30 kg / m², with elevated triglycerides, hypertension) should be subjected to clinical and biochemical monitoring according to local guidelines.There are no studies on the effects of the medicine on the development of children. Use in children under 10 years is not recommended. The product contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency 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, larynx, nosebleeds, constipation, bloating, indigestion, nausea, diarrhea, muscle pain, joint pain, pain in the limbs, muscle cramps, swelling of the joints, back pain, abnormal liver function tests, increase in creatine kinase in the blood. Uncommon: hypoglycaemia, weight gain, anorexia, nightmares, insomnia, dizziness, paresthesia, hypoesthesia, dysgeusia, amnesia, blurred vision, tinnitus, vomiting, pain in the upper and lower abdomen, belching in the return of gastric contents , pancreatitis, hepatitis, urticaria, rash, pruritus, alopecia, neck pain, muscular fatigue, malaise, weakness, chest pain, peripheral edema, fatigue, fever, white blood cells in the urine. Rare: thrombocytopenia, peripheral neuropathy, visual disturbances, cholestasis, angioedema, bullous rash, including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, myopathy, myositis, rhabdomyolysis, tendon problems 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 important (> 3 times ULN) increase in blood transaminases occurred in 0.8% of patients (it was dose-dependent and reversible in all patients). Increased CK activity in the blood (> 3 times above ULN) was noted in 2.5% of patients. A 10-fold increase in CK activity occurred in 0.4% of patients. During treatment with some statins, the following side effects have been reported: sexual dysfunction, depression, a single case of interstitial lung disease, especially during long-term treatment. In children, headache, abdominal pain, increased alanine aminotransferase, elevation of creatine phosphokinase in the blood were common. Based on the available data, it can be expected that the frequency, type and severity of side effects in children will be the same as in adult patients. Data on long-term safety in children are limited.

Orally. The dose should be adjusted individually depending on the purpose of treatment, LDL-cholesterol before treatment and patient's response to treatment. The usual starting dose is 10 mg once a day. Dose modifications should be made every 4 weeks or less frequently. The maximum dose is 80 mg once a day.Primary hypercholesterolemia and mixed hyperlipidemia: 10 mg once a day; efficacy is observed within 2 weeks and the maximum response is usually achieved within 4 weeks and is maintained during long-term treatment.Heterozygous familial hypercholesterolaemia: the recommended starting dose is 10 mg once a day; dose changes should be made every 4 weeks to achieve a 40 mg dose once a day; then the dose can be either increased to a maximum dose of 80 mg once a day or atorvastatin 40 mg once a day in combination with bile acid sequestrants.Homozygous familial hypercholesterolemia: 10-80 mg once a day as adjunctive therapy for other lipid-lowering therapy (eg LDL cholesterol apheresis) or when such treatments are not available.Prevention of cardiovascular diseases: 10 mg once a day; to get the recommended LDL-cholesterol level, higher doses may be necessary. There is no need to change the dosage in patients with renal insufficiency and in the elderly.Children from 10 years. Hypercholesterolemia.The use of the preparation should be under the control of specialist physicians experienced in the treatment of hyperlipidemia in children; Regularly assess the health of patients in terms of treatment effectiveness. The recommended starting dose is 10 mg a day, the dose may be increased to 20 mg a day depending on the response to treatment and tolerability. Data regarding the safety of children at doses above 20 mg (corresponding to approximately 0.5 mg / kg) are limited.
The preparation can be taken at any time of the day, regardless of meals.