Index of drugs

hypercholesterolemia The drug is used as a dietary supplement to lower elevated total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides in adult, adolescent and children from the age of 10 with primary hypercholesterolaemia, including familial hypercholesterolaemia (heterozygous variant) or complex hyperlipidemia ( mixed) (corresponding to Fredrickson type IIa and IIb hiperlipidemia) when the response to diet and other non-pharmacological treatments is inappropriate. The drug is also used to lower total cholesterol and LDL-cholesterol in adult patients with homozygous familial hypercholesterolaemia as a supplement to other lipid-lowering treatments (eg LDL-cholesterol apheresis) or if such treatments are not available.Prevention of cardiovascular diseases. Prevention of cardiovascular events in 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.

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 cholesterol and lipoproteins in the blood 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 C_max over time 1-2 h. The absolute bioavailability is about 12% and the systemic HMG-CoA reductase inhibitory activity is about 30%. W ≥ 98% bound to plasma proteins. It is metabolised in the liver by cytochrome CYP3A4 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.

Hypersensitivity to atorvastatin or to the other components of the drug. Active liver disease or unexplained, permanently elevated serum transaminase levels exceeding 3 times the upper limit of normal (ULN). Pregnancy, breastfeeding period. Women of childbearing potential not using appropriate contraceptives.

Before and during the treatment, liver function tests should be performed. Patients who develop signs and symptoms of liver damage should undergo liver function tests. Patients who have increased aminotransferase levels should be monitored until these abnormalities resolve. In the case of persistent elevation of aminotransferases, greater than 3-fold GGN, a dose reduction or withdrawal of atorvastatin is recommended.Caution should be exercised when administering the drug to patients who consume significant amounts of alcohol and / or liver disease. In patients with a history of haemorrhagic stroke or a lacunar infarct (stroke), the risk / benefit ratio for atorvastatin 80 mg is not determined, and the potential risk of haemorrhagic stroke should be carefully considered before treatment is started. Atorvastatin should be prescribed cautiously to patients who have predisposing factors for rhabdomyolysis. The risk of initiating treatment should be considered in relation to the potential benefits and the creatine kinase (CK) activity should be determined in the following situations before starting treatment: renal dysfunction, hypothyroidism, hereditary muscular or familial history disorder, muscle toxicity during prior statin therapy or a history of fibrate, history of liver disease and (or) large amounts of alcohol in the elderly (the need for such tests should be considered depending on other risk factors predisposing to rhabdomyolysis) and in situations where the concentration of blood may be increased, eg, interactions and patients with SLCO1B1 polymorphism (in these patients, exposure to atorvastatin is 2.4-fold higher and possible genetic impairment of atorvastatin uptake by the liver; the quantity of the drug is unknown). If the CK activity is significantly elevated in the initial assay (> 5 times ULN), treatment should not be started. In the event of muscle aches, cramps or muscle weakness, 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 treatment should be considered. If clinical signs resolve and CK activity returns to normal, re-introduction of atorvastatin or other statins into the smallest dose and under strict control may be considered. Treatment with atorvastatin must be discontinued if CK levels increase significantly (> 10 times ULN) or if rhabdomyolysis is suspected or suspected. If there is a suspicion that the patient develops interstitial lung disease, statin therapy should be discontinued. It is believed that statins can increase blood sugar levels and in some patients at high risk of developing diabetes can cause hyperglycaemia when adequate prevention of diabetes is maintained. However, this risk is balanced by reducing the risk of cardiovascular events, therefore statin therapy should not be discontinued. Patients at risk (fasting Glucose 5.6 to 6.9 mmol / l, BMI> 30kg / m2, elevated levels of triglycerides, hypertension) should be under the control of both clinical status and biochemical tests in accordance with national guidelines. The experience of using the drug in children between 6-10 years is limited. Atorvastatin is not indicated for the treatment of patients under 10 years of age.

The drug is contraindicated for use during pregnancy, while breastfeeding and in women trying to become pregnant or suspecting that they are pregnant. Treatment should be stopped for the duration of pregnancy or until it is determined that the patient is not pregnant.

Common: rhinitis, allergic reactions, hyperglycemia, headache, sore throat and larynx, nosebleeds, constipation, bloating, indigestion, nausea, diarrhea, muscle pain, joints, limbs, muscle cramps, swollen joints, pain back, abnormal liver function tests, increased blood creatine kinase. Uncommon: thrombocytopenia, hypoglycaemia, weight gain, anorexia, nightmares, insomnia, dizziness, paresthesia, hypoesthesia, dysgeusia, amnesia, blurred vision, tinnitus, vomiting, upper and lower abdominal pain, belching, inflammation pancreatitis, hepatitis, urticaria, skin rash, pruritus, alopecia, neck pain, muscular fatigue, malaise, weakness, chest pain, peripheral edema, fatigue, fever, white blood cells in the urine.Rare: peripheral neuropathy, blurred vision, cholestasis, angioedema, bladder dermatitis including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, myopathy, myositis, rhabdomyolysis, tendon disease, sometimes complicated by tendon rupture. Very rare: anaphylaxis, hearing loss, liver failure, gynecomastia. The following side effects have been reported during treatment with some statins: sexual dysfunction, depression, isolated cases of interstitial lung disease (especially during long-term treatment), diabetes (frequency depends on the presence of risk factors - fasting glucose ≥5,6 mmol / l, BMI> 30 kg / m², elevated levels of triglycerides, the presence of hypertension). In children - often: headache, abdominal pain, increased ALT, increased 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.

Orally. The dose should be adjusted individually depending on the purpose of treatment, LDL-cholesterol before treatment and patient's response to treatment.Adults: the starting dose is usually 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 hypercholesterolaemia: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.Children and adolescents ≥10 years. hypercholesterolemia: 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 daily dose of atorvastatin should be taken once a day, at any time of the day, regardless of meals.