Index of drugs

Supplementing dietary therapy to reduce elevated total cholesterol, LDL cholesterol, apolipoprotein B or triglycerides in patients with primary hypercholesterolemia, heterozygous familial hypercholesterolaemia or mixed hyperlipidemia (corresponding to Fredrickson's type IIa and IIb) if the diet and other nonpharmacological measures were insufficiently effective. In patients with homozygous familial hypercholesterolaemia, as adjunctive therapy with other cholesterol-lowering medicines (LDL) or in the case when other therapeutic methods are not effective enough.

1 tabl powl. contains 10 mg, 20 mg or 40 mg of Atorvastatin in the form of a 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 blood cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase activity and cholesterol synthesis in the liver. Atorvastatin also increases the number of hepatic receptors for LDL on the cell surface, leading to increased uptake and catabolism of LDL. Atorvastatin reduces the formation of LDL and the amount of LDL particles. It leads to a significant and sustained increase in LDL receptor activity and preferably changes the quality of circulating LDL molecules. Atorvastatin reduces LDL cholesterol in patients with homozygous familial hypercholesterolaemia who do not usually respond to lipid-lowering drugs. Atorvastatin reduces total cholesterol (by 30-46%), LDL cholesterol (by 41-61%), apolipoprotein B (by 34-50%) and triglycerides (by 14-33%) and causes a differentiated, dose-dependent increase HDL cholesterol and apolipoprotein A1. Following oral administration, atorvastatin is rapidly absorbed from the gastrointestinal tract, reaching its highest concentration in the blood within 1-2 hours. Absolute bioavailability is approximately 12%, and the systemic availability of HMG-CoA reductase inhibitory activity is 30% (which is associated with drug clearance through the cells of the mucous membrane of the stomach and intestines before it gets into the circulation and the effect of the first pass). Plasma proteins are more than 98% bound. 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 inhibitory effect on HMG-CoA reductase is attributed to active metabolites. The drug is mainly excreted in the bile. The average T0.5 is about 14 h. The half-life of the 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 or its effectiveness. The concentration of atorvastatin and its active metabolites in the blood is significantly increased (Cmax approximately 16 times and AUC approximately 11 times) in patients with chronic alcohol-related liver injury (Childs-Pugh B).

Hypersensitivity to atorvastatin or any of the excipients. Active liver disease or persistent elevated serum transaminase levels exceeding 3 times the upper limit of the value considered normal. Myopathy. Pregnancy. Breastfeeding period. Women of childbearing potential not using appropriate methods of contraception.

Caution should be exercised when using the medicine in patients who consume significant amounts of alcohol and / or with a history of liver disease. If transaminase elevations persist (greater than 3 times the normal value), the dose should be reduced or discontinued. Atorvastatin can, in very rare cases, affect skeletal muscle and cause muscle pain, myositis and myopathy, which can lead to rhabdomyolysis, a potentially life threatening condition characterized by a significant increase in CK kinase (> 10-fold above the upper limit of the value considered as normal), myoglobinemia and myoglobinuria, which can lead to renal failure. Special care should be taken to determine CK activity in patients predisposed to rhabdomyolysis, i.e.in patients with impaired renal function, hypothyroidism, genetic or history-related myopathy with myopathy associated with the use of statins or fibrates in the past, with liver failure and / or alcohol-abusing patients and the elderly (> 70 years); in these groups of patients, the risks and benefits of treatment should be considered. CK activity should be measured before starting treatment - if the CK activity is significantly elevated (> 5 times above the upper limit of the value considered normal), treatment should not be started. Drug administration must be discontinued if CK levels increase significantly (> 10 times the upper limit of the normal value) and if there are muscle symptoms (muscle pain, spasm or muscle weakness, especially if these symptoms are accompanied by general weakness and fever) and CK elevation> 5 times above the upper limit of the value considered normal; if the muscle-related ailments are significantly intensified and cause discomfort on a daily basis, discontinuation of treatment should be considered even if the CK activity does not exceed 5 times the upper limit of the value considered normal. If the symptoms subside and CK activity returns to normal, treatment with atorvastatin or other statins may be considered if minimal doses are used and the patient's condition is closely monitored. The risk of rhabdomyolysis increases with the use of atorvastatin in combination with such drugs as cyclosporine, Erythromycin, Clarithromycin, Itraconazole, ketoconazole, nefazodone, niacin, gemfibrozil and other fibrates, and HIV protease inhibitors.

The use of the drug during pregnancy and breast-feeding is contraindicated. Women of childbearing potential should use effective methods of contraception. The safety of atorvastatin during pregnancy and breastfeeding has not been established.

Common: constipation, bloating, dyspepsia, nausea, diarrhea; hypersensitivity; insomnia, pain and dizziness, paresthesia, reduced sensitivity to touch; skin rash, pruritus; muscular pains, joint pain; weakness, chest pain, back pain, peripheral edema. Uncommon: anorexia, vomiting; thrombocytopenia; alopecia, hyperglycemia or hypoglycaemia, pancreatitis; amnesia, peripheral neuropathy; tinnitus; hives; myopathy; impotence; fatigue, weight gain. Rare: hepatitis, jaundice congestion; myositis, rhabdomyolysis. Very rare: anaphylactic reactions, angioneurotic edema, bullous rash (including erythema multiforme, Stevens-Johnson syndrome and toxic necrotic epidermal separation).

Orally.Adults. The dose should be adjusted individually based on the baseline LDL cholesterol, the purpose of treatment and the patient's response to treatment. The starting dose is 10 mg once a day. Dose modification should be carried out at intervals of at least 4 weeks or longer. The maximum daily dose is 80 mg. In patients with known ischemic heart disease and in patients with an increased risk of ischemic episodes, the goal of treatment is to achieve LDL-cholesterol <3 mmol / l (or 115 mg / dl) and total cholesterol is <5 mmol / l (or 190 mg / dl).Primary hypercholesterolemia and mixed hyperlipidemia: in most patients, a dose of 10 mg once a day is sufficient; the onset of efficacy is observed within 2 weeks and the maximum therapeutic effect is usually achieved within 4 weeks and is maintained during long-term treatment.Heterozygous familial hypercholesterolemia: the starting dose is 10 mg once a day; dose adjustments should be made no more frequently than 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 a supportive treatment for other lipid-lowering therapies or if treatment with other methods did not bring the expected results. There is no need to change the dosage in patients with renal insufficiency and in the elderly.Children: the use of the preparation should be carried out by specialist doctors; experience in the treatment of children is limited to a small group of patients (4-17 years of age) with severe hyperlipidemia, such as homozygous familial hypercholesterolaemia - the safety data regarding the period of puberty in this group of patients has not been evaluated. The recommended starting dose is 10 mg daily, the dose may be increased to 80 mg daily depending on the response and tolerability of the medicine.
The daily dose should be taken in full, once a day, regardless of the time of the day, with or without food.