Index of drugs

hypercholesterolemia: supplementation of dietary therapy to lower elevated total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides in adults, adolescents and children 10 years of age or older with primary hypercholesterolaemia, including heterozygous familial hypercholesterolaemia, or complex (combined) 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: prevention of cardiovascular events in adult patients at risk of the first event being assessed as high, along with measures to reduce other risk factors.

1 tabl powl. contains 10 mg, 20 mg or 40 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 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%. At> 98%, it binds 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 the active substance or to any of the excipients. Active liver disease or unexplained, permanently elevated blood aminotransferase levels exceeding the upper limit of normal (ULN) 3-fold. 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-fold of GGN, it is recommended to reduce the dose of the drug or its discontinuation.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 increased risk was mainly observed in patients with previous hemorrhagic stroke or 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. Patients with a high risk of diabetes (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 national guidelines. Caution should be exercised when using atorvastatin in patients with predisposing factors for rhabdomyolysis: renal dysfunction, hypothyroidism, muscle disease or familial history of muscle disease, muscle damage associated with prior intake of statins or fibrates, and history of liver disease and (or) in patients consuming large amounts of alcohol, in elderly patients (> 70 years) and in situations where blood levels of the drug may be increased (eg, interactions and patients with a polymorphism in the OATP1B1 encoding gene - in these patients the exposure atorvastatin can be increased 2.4-fold). In these groups, creatine kinase (CK) should be measured before treatment - if the CK activity exceeds 5-fold GGN, 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. The administration of medication must be discontinued if there is a significant increase in CK (> 10 times ULN), if rhabdomyolysis is present or suspected, and if muscle symptoms occur (muscle pain, spasm or muscle weakness, especially if accompanied by general malaise or fever), which is accompanied by an increase in CK> 5 times ULN (if the muscle symptoms are severe and cause patient discomfort on a daily basis, then even if the CK activity remains ≤5 times ULN, discontinuation of treatment 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. The risk of rhabdomyolysis increases with the concomitant use of drugs increasing blood levels 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 blood levels of atorvastatin, a lower starting dose and / or maximum atorvastatin and clinical control are recommended. Co-administration of atorvastatin and fusidic acid is not recommended. The statin therapy should be discontinued if the patient is suspected of having interstitial lung disease. There are no studies on the effects of the medicine on the development of children. Use in children under 10 years is not recommended. Due to the lactose content, the preparation should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

The preparation is contraindicated in pregnant women, in women of childbearing age who do not use effective methods of contraception and during breastfeeding.

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: 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, presence of white blood cells in the urine. Rare: thrombocytopenia, peripheral neuropathy, blurred vision, cholestasis, angioedema, bullous rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, myopathy, myositis, rhabdomyolysis, tendon problems sometimes complicated by tendon rupture. Very rare: anaphylaxis, hearing loss, liver failure, gynecomastia. During treatment with some statins, the following side effects have been reported: sexual dysfunction, depression, isolated cases of interstitial lung disease (especially during long-term treatment), diabetes mellitus. 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 the same as 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. 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 hypercholesterolaemia10-80 mg once daily as adjuvant 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. Data on the use of the drug in children aged 6-10 years are limited - it is not recommended to use the preparation in this age group.Special groups of patients. There is no need to change the dosage in patients with renal insufficiency and in the elderly.
The daily dose of atorvastatin should be taken once a day, at any time of the day, regardless of meals.