Index of drugs

hypercholesterolemia. Supplementing the diet to reduce elevated total cholesterol, LDL cholesterol (LDL-C), apolipoprotein B and triglycerides in adults, adolescents and children 10 years or older with primary hypercholesterolaemia, including familial hypercholesterolaemia (heterozygous variant) or complex hyperlipidemia (mixed) (corresponding to Fredrickson's IIa and IIb types), when the response to diet and other non-pharmacological treatments is insufficient. Reduction of total and LDL-C cholesterol in patients with familial homozygous hypercholesterolemia, in addition to other lipid-lowering treatments (eg LDL 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, 40 mg or 80 mg of Atorvastatin (as 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 cholesterol and lipoproteins in the blood by inhibiting HMG-CoA reductase, which in turn inhibits cholesterol biosynthesis in the liver. In addition, it increases the number of LDL receptors on the surface of liver cells, thus improving the uptake and catabolism of LDL. 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 LDL (LDL-C) cholesterol in patients with homozygous familial hypercholesterolaemia who have not generally responded to lipid-lowering therapy. Atorvastatin reduces total cholesterol (by 30-46%), LDL-C (by 41-61%), apolipoprotein B (by 34-50%) and triglycerides (by 14-33%) and increases HDL-C 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 persistent unexplained high 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.

Atorvastatin should be used with caution in patients with predisposing factors for myopathy or rhabdomyolysis such as: renal dysfunction, hypothyroidism, history of hereditary muscular disorders or a family history of muscle toxicity during prior therapy with statin or a fibrate history, liver disease in the history and / or intake of 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 - higher 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. 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 had recently had a stroke or transient ischemic attack, haemorrhagic strokes were more frequent in patients treated with atorvastatin 80 mg, compared to the placebo group. Increased risk has been observed mainly in patients with pre-existing hemorrhagic 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. Experience with the use of atorvastatin in children aged 6-10 years is limited, therefore the drug is not indicated for use in children <10 years of age. There are no studies on the effects of the medicine on the development of children.

Use during pregnancy and breast-feeding is contraindicated. Patients of childbearing age should use effective methods of contraception.

Common: inflammation of the nose and throat, allergic reactions, hyperglycemia, headache, sore throat and larynx, nosebleeds, constipation, flatulence, indigestion, nausea, diarrhea, muscle pain, joint pain, limb pain, muscle cramps, swollen joints, pain backache, abnormal liver function tests, increased CK activity. Uncommon: hypoglycaemia, weight loss, anorexia, nightmares, insomnia, dizziness, paresthesia, sensation impairment, taste disturbance, amnesia, blurred vision, tinnitus, vomiting, upper and lower abdominal pain, belching, pancreatitis , hepatitis, urticaria, pruritus, rash, alopecia, neck pain, muscular fatigue, malaise,weakness, chest pain, peripheral edema, fatigue, fever, presence of leucocytes in the urine. Rare: thrombocytopenia, peripheral neuropathy, visual impairment, cholestasis, angioedema, bullous 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. 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. Side effects characteristic of statins: sexual dysfunction, depression, isolated cases of interstitial lung disease (especially during long-term treatment), diabetes (frequency depends on the presence or absence of risk factors: glycemia ≥5,6 mmol / l, BMI> 30 kg / m², increased triglycerides, hypertension).Children and youth. Common: headache, abdominal pain, increased ALT, increased CK activity. 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.

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 hypercholesterolaemia and compound hyperlipidaemia (mixed): 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.Familial hypercholesterolemia heterozygous: 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.Familial homozygous hypercholesterolemia10-80 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.Special groups of patients. There is no need to change the dosage in patients with impaired renal function and in the elderly.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 should not be used in 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, regardless of meals.