Index of drugs

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

1 tabl powl. contains 10 mg, 20 mg, 40 mg or 80 mg of Atorvastatin (as Calcium salt).

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. Total 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 the active substance or to any of the excipients. Active liver disease or unexplained, persistently elevated serum transaminase levels exceeding 3-fold GGN. Pregnancy, breastfeeding and women of childbearing potential not using effective methods of contraception.

The liver function check should be performed before and during the treatment period. Patients who develop signs and symptoms of liver damage should undergo liver function tests.Patients who have increased aminotransferase levels should be monitored until the disorder is resolved. In the case of persistent elevation of aminotransferases, greater than 3-fold GGN, a dose reduction or discontinuation of the drug is recommended. Caution should be exercised when administering the drug to patients who consume significant amounts of alcohol and / or liver disease. In patients without coronary disease with recent stroke or who had transient ischemic stroke (TIA), there was a higher incidence of haemorrhagic stroke in patients who received 80 mg of atorvastatin when compared to placebo. The increased risk was particularly evident in patients with a history of hemorrhagic stroke or a history of lacunar infarction. In these patients, the risk-benefit balance of atorvastatin 80 mg is not known and the potential risk of haemorrhagic stroke should be carefully considered before starting treatment. Atorvastatin should be prescribed with caution to patients with predisposing factors for rhabdomyolysis (these patients should be evaluated for CK activity before switching to statin therapy): renal dysfunction; hypothyroidism; muscular diseases or the occurrence of hereditary muscular diseases in a family history; previous occurrence of muscle damaging effects following the use of statins or fibrates; liver disease and / or large amounts of alcohol; in the elderly (over 70 years) the need to perform such tests should be considered in the context of other risk factors predisposing to rhabdomyolysis; situations in which increased plasma concentrations may occur, such as side effects and special patient groups, including genetic subpopulations (the polymorphism of the OATP1B1 encoding gene is associated with a 2.4-fold higher exposure to atorvastatin). In such situations, the risk of starting treatment with respect to possible benefits should be considered, and clinical symptoms should be monitored. If the CK activity is significantly elevated in the initial determination (> 5 times ULN), treatment should not be started. Patients treated with atorvastatin should report muscle pain, muscle cramps or weakness immediately, especially if accompanied by general malaise or fever. If these symptoms occur, CK activity should be determined - if it is significantly elevated (> 5 times ULN), the drug should be discontinued. If the muscle symptoms are significantly increased and cause patient discomfort on a daily basis, then even if the CK activity is ≤5 times ULN, discontinuation of therapy should be considered. 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. Treatment with atorvastatin must be discontinued if there is a significant increase in CK (> 10 times ULN) or when rhabdomyolysis occurs or is suspected. If you suspect you have interstitial lung disease, stop using statin therapy. Statin drugs increase blood Glucose levels and in some patients with a high risk of developing diabetes in the future, they may cause hyperglycemia of an intensity requiring appropriate diabetes care. This risk is however outweighed by the benefit of reducing the risk of developing vascular disease, so statin therapy should not be discontinued. Patients at risk (patients with fasting glucose from 5.6 to 6.9 mmol / l, BMI> 30 kg / m², with increased triglycerides, hypertension) should be subjected to clinical and biochemical monitoring in accordance with the guidelines. There are no studies on the effects of the medicine on the development of children. Data on the use of the drug in children aged 6-10 years are limited. The use of atorvastatin in children under the age of 10 years is not recommended.

The use of the drug during pregnancy and breastfeeding is contraindicated. Women of childbearing age should use effective methods of contraception during treatment.

Common: nasopharynx, allergic reactions, hyperglycemia, headache, sore throat and larynx, nosebleeds, constipation, flatulence, dyspepsia, nausea, diarrhea, muscle pain, arthralgia, limb pain, muscle cramps, swollen joints, back pain, abnormal liver function tests, increased blood creatine kinase. Uncommon: hypoglycaemia, weight gain, anorexia, nightmares, insomnia, dizziness, paresthesia, hypoesthesia, dysgeusia, amnesia, blurred vision, tinnitus, vomiting, epigastric and abdominal pain, belching, 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, blurred vision, cholestasis, angioneurotic edema, bladder rash (including erythema multiforme), Stevens-Johnson syndrome and toxic epidermal necrolysis, myopathy, myositis, rhabdomyolysis, tendon diseases (sometimes complicated by tendon rupture) . Very rare: anaphylaxis, hearing loss, liver failure, gynecomastia. Increases in serum transaminases have been observed with atorvastatin. These changes were mostly mild, transient and did not require discontinuation of therapy. Clinically significant (> 3 times ULN), serum transaminases increased in 0.8% of patients receiving atorvastatin. It was dependent on the dose of the drug and reversible in all patients. Increased serum CK (> 3 times ULN) was observed in 2.5% of patients receiving atorvastatin. Increased CK (> 10 times ULN) occurred in 0.4% of patients receiving atorvastatin. Side effects reported for some statins: sexual dysfunction, depression, exceptionally cases of interstitial lung disease especially during long-term treatment, diabetes: frequency depends on the presence or absence of risk factors (glycemia ≥ 55.6 / l, BMI> 30 kg / m², increase in triglycerides, hypertension).Children and youth. Common: headache, abdominal pain, increased ALT, increased creatine phosphokinase in the blood. 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. Doses should be adjusted individually depending on the concentration of LDL-C cholesterol before treatment, the intended therapeutic goal 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. For most patients, a dose of 10 mg once a day is sufficient. Therapeutic efficacy is observed within 2 weeks, and the maximum response is usually achieved within 4 weeks. It is maintained during long-term treatment.Heterozygous familial hypercholesterolaemia. The recommended initial dose is 10 mg a day. Doses should be determined individually and dose changes should be made every 4 weeks, up to 40 mg daily. You can either increase the dose to a maximum dose of 80 mg daily or give atorvastatin 40 mg daily in combination with bile acid sequestrants.Homozygous familial hypercholesterolaemia. 10-80 mg a day. Atorvastatin should be used in these patients as adjunctive therapy to other lipid-lowering therapies (eg LDL-C apheresis), or when such treatments are not available.Prevention of cardiovascular diseases. 10 mg / day. To obtain LDL-C, higher doses may be required for current guidelines. No dose adjustment is required in patients with renal insufficiency or in elderly patients.Children and youth. Hypercholesterolemia: use of the drug in children should be under the control of specialized doctors experienced in the treatment of hyperlipidemia in children. Regularly assess your health. For patients aged 10 years or older, the recommended starting dose is 10 mg per day. The dose may be increased to 20 mg a day depending on the response to treatment and tolerance of the drug in children.Safety data for children taking doses higher than 20 mg, equivalent to 0.5 mg / kg, are limited. Data on the use of the drug in children aged 6-10 years are limited. The use of atorvastatin in children under the age of 10 years is not recommended. The use of other forms / strengths of this drug may be more appropriate in this group of patients. The drug is given once, at any time of the day, regardless of meals.