Index of drugs

hypercholesterolemia. Supplementing dietary therapy to lower elevated total cholesterol (TC), LDL cholesterol (LDL-C), apolipoprotein B and triglycerides in adults, adolescents and children aged 10 years and above with primary hypercholesterolemia, including familial hypercholesterolemia ( heterozygous form) or mixed hyperlipidemia (corresponding to type II a or type II b according to Fredrickson's classification), if the response to diet and other non-pharmacological measures is insufficient. It is also indicated for use to lower total and LDL cholesterol in adults with homozygous familial hypercholesterolaemia in addition to other cholesterol-lowering treatments (eg LDL apheresis) or in cases where such treatments are not available.Prevention of diseases of the cardiovascular system. In the alternative, to limit other risk factors in the prevention of cardiovascular events in adult patients at high risk of the first cardiovascular event.

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 limiting the rate of cholesterol synthesis, catalyzing 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, which in turn inhibits hepatic cholesterol biosynthesis, and increases the number of LDL receptors on the surface of the hepatocytes cell membrane, thereby enhancing LDL uptake and catabolism. It reduces the production of LDL and the amount of LDL particles, induces a significant and sustained increase in LDL receptor activity and preferably changes the quality of circulating LDL molecules. It reduces the level of LDL cholesterol in patients with homozygous familial hypercholesterolaemia who did not usually respond to lipid-lowering therapy. Atorvastatin reduces total cholesterol (by 30-46%), LDL cholesterol (by 41-61%), apolipoprotein B (by 34-50%) and triglycerides (by 14-33%) and increases HDL cholesterol and apolipoprotein A1. Atorvastatin is rapidly absorbed from the gastrointestinal tract, reaching C_max after 1-2 h. The absolute bioavailability is about 12%, and the systemic activity inhibiting HMG-CoA reductase is about 30%. 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 β-oxidation products that are further metabolised by glucuronidation. About 70% of the HMG-CoA reductase inhibitory activity is attributed to active metabolites. The drug is mainly excreted in the bile. Medium T_0,5 is approximately 14 h. The half-life of HMG-CoA reductase inhibitors 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 (C_max approximately 16 times and AUC approximately 11 times) in patients with chronic alcohol-related liver injury (Childs-Pugh B). The polymorphism in the OATP1B1 encoding gene (SLCO1B1 c.521CC) is associated with a 2.4-fold greater exposure to atorvastatin (AUC) than in non-carriers of this genotype variant (c.521TT).

Hypersensitivity to atorvastatin or any of the excipients. Active liver disease or unexplained, persistent blood aminotransferase levels exceeding 3 times the upper limit of normal (ULN). Pregnancy. Breastfeeding period. Women of childbearing potential not using effective methods of contraception.

Atorvastatin should be used with caution in patients with predisposing factors for myopathy or rhabdomyolysis such as: renal dysfunction, hypothyroidism, muscle disease or history of hereditary muscular diseases, signs of muscle damage following the use of another HMG-CoA reductase inhibitor or fibrates , history of liver disease and / or large amounts of alcohol, age> 70 years, situations in which blood levels may increase (eg patients with a polymorphism in the OATP1B1 - SLCO1B1 c.521CC gene - greater exposure to atorvastatin).The risk of myopathy may also be increased if atorvastatin interacts with other drugs (pharmacokinetic or pharmacodynamic interactions, see also interactions). In patients with an increased risk of myopathy, the risks and benefits of treatment should be considered and patients should be monitored during treatment; before initiation of therapy, creatine kinase (CK) activity should be determined. If the CK activity is significantly increased during the first determination (> 5 x ULN), follow-up should be performed after 5-7 days. Treatment should not be initiated if the control CK> 5 x ULN. If unexplained muscle pain, muscle weakness or muscle spasms occur during treatment with Atorvastatin, especially when accompanied by malaise or fever, CK activity should be determined. Treatment should be discontinued if CK activity is significantly increased (> 5 times ULN) or if the muscle symptoms are severe and cause discomfort during daily activities (even if CK activity ≤5 times ULN). Once the clinical symptoms have subsided and CK levels are reduced to normal, re-use of atorvastatin or another HMG-CoA inhibitor at the lowest dose may be considered with close observation of the patient. Treatment with atorvastatin must be discontinued if there is a significant increase in CK (> 10 x ULN) or when rhabdomyolysis occurs or is suspected. Very rare cases of immunological necrotizing myopathy (IMNM) have been reported, which are clinically characterized by permanent weakness of the proximal muscles and elevated CK levels during or after withdrawal of statins. Before initiating treatment with atorvastatin, check liver function tests and monitor liver function during therapy. 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-fold of GGN, it is recommended to reduce the dose of the drug or its discontinuation. The drug should be used with caution in patients who are abusing alcohol and / or have a history of liver disease. In patients without ischemic heart disease who have recently suffered a stroke or transient ischemic attack, ischemic stroke was more frequent in patients treated with atorvastatin 80 mg compared to the placebo group. The increased risk was mainly observed in patients with previous ischemic stroke or lacunar infarction - in these patients, the potential risk of haemorrhagic stroke should be carefully considered before initiating treatment with atorvastatin 80 mg. If the patient is suspected of developing interstitial lung disease (manifested by dyspnoea, dry cough, general deterioration of health - fatigue, weight loss, fever), statin therapy should be discontinued. Statins can cause an increase in blood Glucose and in some patients at risk for developing diabetes can cause hyperglycaemia, which requires proper diabetes care. However, this risk should not be a reason for discontinuation of statin therapy, because the benefits of reducing the risk of vascular disorders due to the use of statins are greater. Patients at risk (with a fasting glucose level of 5.6-6.9 mmol / l, BMI> 30 kg / m², increased triglycerides, hypertension) should be monitored both clinically and biochemically in accordance with national guidelines. There is limited experience in the use of atorvastatin in children aged 6-10 years, therefore the medicine is not recommended for use in children <10 years of age. There are no studies on the effects of the medicine on the development of children.

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, bloating, indigestion, nausea, diarrhea, muscle pain, arthralgia, limb pain, muscle spasms, swollen joints , back pain, abnormal liver function tests, increased blood creatine kinase.Uncommon: hypoglycaemia, weight gain, anorexia, nightmares, insomnia, dizziness, paresthesia, hypoaesthesia, dysgeusia, amnesia, blurred vision, tinnitus, vomiting, lower abdominal and upper abdomen pain, belching, pancreatitis, hepatitis, urticaria, pruritus, rash, alopecia, neck pain, muscular fatigue, malaise, weakness, chest pain, peripheral edema, fatigue, fever, white blood cells in the urine. Rare: thrombocytopenia, peripheral neuropathy, visual impairment, congestive jaundice, angioedema, bullous rash (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), myopathy, myositis, rhabdomyolysis, tendon degeneration (sometimes complicated by tendon rupture) ). Very rare: anaphylaxis, hearing loss, liver failure, gynecomastia. Not known: immunodifiable necrotic myopathy (IMNM). 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.Children and youth. Common: 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 the same as in adult patients. Data on long-term safety in children are limited. Side effects characteristic of statin drugs: sexual dysfunction, depression, isolated cases of interstitial lung disease, especially during long-term treatment, diabetes.

Orally. The dose should be adjusted individually depending on the purpose of treatment, LDL-cholesterol before treatment and patient's response to treatment. Before and during the treatment, the patient should use a standard low cholesterol diet. 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: usually 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.Special groups of patients. There is no need to change the dosage in patients with renal insufficiency and in the elderly. For patients taking concomitant medications that may increase blood levels of atorvastatin, the recommended starting dose is 10 mg a day.Children ≥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 daily, the dose may be increased to 20 mg daily, 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. Atorvastatin is not indicated for children <10 years of age.Way of giving. The daily dose of atorvastatin is given as a single dose only. The preparation can be taken at any time of the day, with or without food.