Index of drugs

Treatment of hypercholesterolemia. Primary hypercholesterolemia (type IIa, excluding heterozygous familial hypercholesterolaemia) or mixed dyslipidemia (type IIb) in adults, adolescents and children aged 10 years or older, as a supplement to the diet when the response to diet and other non-pharmacological treatments (e.g. physical, weight loss) is insufficient. Familial homozygous hypercholesterolemia, as a supplement to diet and other lipid-lowering treatments (eg LDL apheresis) or if other treatments are inappropriate.Prevention of major cardiovascular events: in patients at high risk for the first cardiovascular event, in addition to the methods used to correct other risk factors.

1 tabl powl. contains 5 mg, 10 mg, 20 mg or 40 mg of Rosuvastatin in the form of a Calcium salt; tablets contain lactose.

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that determines the rate of conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor to cholesterol. Rosuvastatin increases the number of receptors for LDL on the surface of liver cells, which facilitates the capture and catabolism of LDL, inhibits the production of VLDL in the liver, leading to a reduction in the total amount of LDL and VLDL. After oral administration, rosuvastatin reaches C_max after about 5 hours. Absolute bioavailability is about 20%. It binds to plasma proteins, mainly to albumin, in about 90%. It is metabolized to a small extent (10%). As with other HMG-CoA reductase inhibitors, rosuvastatin is taken up by liver cells through the OATP-C - a transport compound in the membrane of liver cells; this is an important compound in the process of eliminating rosuvastatin in the liver. About 90% of rosuvastatin is excreted unchanged with faeces (both absorbed and unabsorbed). The remaining part is excreted in the urine, about 5% in unchanged form. T_0,5 in the elimination phase, it is about 19 hours.

Hypersensitivity to rosuvastatin or other components of the preparation. Active liver disease, including unexplained, persistently elevated serum transaminase activity and more than 3-fold increase above the upper limit of normal (ULN) activity of one of them. Severe renal impairment (creatinine clearance <30 ml / min). Myopathy. Simultaneous treatment with cyclosporin. Pregnancy. Breastfeeding period. Women of childbearing potential not using effective methods of contraception. In addition, the 40 mg dose is contraindicated in patients with predisposing factors for myopathy or rhabdomyolysis; they include: moderate renal impairment (creatinine clearance <60 ml / min), hypothyroidism, genetically determined muscular disease in a patient or members of his family, signs of muscle damage after using another HMG-CoA reductase inhibitor or a fibrate drug, alcohol abuse, situations in which blood levels may increase, Asian origin, concomitant use of fibrates.

Rosuvastatin should be used with caution in patients with predisposing factors for myopathy or rhabdomyolysis such as: renal dysfunction, hypothyroidism, genetically determined muscular disease in a patient or members of his family, signs of muscle damage after using another HMG-CoA reductase inhibitor or fibrates , alcohol abuse, age> 70 years, situations where blood levels may rise (eg in Asian patients with rosuvastatin exposure increased). The risk of myopathy may be increased also when interacting with Simvastatin with other drugs (pharmacokinetic or pharmacodynamic interactions, see also contraindications and interactions). In groups of patients with an increased risk of myopathy, the risk and possible benefits of treatment should be considered, and the patient should be monitored during treatment.Before initiating rosuvastatin therapy, creatine kinase (CK) should be measured; if it is significantly increased (> 5 x ULN), follow-up should be carried out after 5-7 days. Treatment should not be initiated if the control CK> 5 x ULN. If you experience unexplained muscle pain, muscle weakness or muscle cramps during rosuvastatin treatment, especially if you feel unwell or have a fever, then 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-treatment with rosuvastatin or another HMG-CoA inhibitor at the lowest dose can be considered with close observation of the patient. If the patient does not have clinical symptoms, routine CK activity monitoring is not necessary. Do not use the product if you have severe, severe symptoms indicative of myopathy or predisposing to secondary renal failure as a result of rhabdomyolysis (e.g., sepsis, hypotension, extensive surgery, trauma, severe metabolic, hormonal and electrolyte disturbances or uncontrolled seizures) ). The drug should be used with caution in patients who are abusing alcohol and / or have a history of liver disease. It is recommended that liver function tests be performed before treatment and 3 months after its initiation. The drug should be discontinued or the dose reduced if the aminotransferase activity is more than 3-fold greater than ULN. In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, appropriate treatment of the underlying disease should be initiated prior to treatment initiation. Due to the increased risk of proteinuria, patients undergoing 40 mg should be considered for monitoring renal function during routine follow-up visits. 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. In patients with fasting Glucose levels of 5.6-6.9 mmol / l, rosuvastatin treatment may increase the risk of developing diabetes. Experience regarding the use of rosuvastatin in children <10 years of age is limited to a small number of patients (between 8 and 10 years of age) with familial homozygous hypercholesterolemia, therefore the drug is not recommended for use in children <10 years of age. Experience regarding the use of rosuvastatin in children and adolescents aged 10-17 years is limited to one year of use; after 52 weeks of treatment, no effect on growth, weight, BMI or sexual maturity was detected, however, the long-term effect of rosuvastatin (> 1 year) on puberty is unknown; increase in creatinine kinase> 10 x ULN and muscle symptoms following exercise or increased physical activity were observed more frequently in children and adolescents compared to adult patients. Due to the lactose content, the drug should not be used in patients with rare hereditary galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose.

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

Common: diabetes (mainly in patients whose fasting glucose is ≥5,6 mmol / l), headache, dizziness, constipation, nausea, abdominal pain, muscle pain, asthenia. Uncommon: pruritus, rash, urticaria. Rare: hypersensitivity reactions (including angioneurotic edema), pancreatitis, myopathy and rhabdomyolysis. In addition, the following activities have been reported on the market following the introduction of rosuvastatin - rare: elevation of aminotransferases; very rare: polyneuropathy, memory loss, jaundice, hepatitis, arthralgia, hematuria; frequency unknown: cough, dyspnea, diarrhea, Stevens-Johnson syndrome, edema. Proteinuria and dose-dependent increases in creatine kinase activity were also observed.The following side effects have been reported with some statins: depression, sleep disorders (including insomnia and nightmares), sexual dysfunction, interstitial lung disease (especially during long-term treatment). The incidence of rhabdomyolysis, severe renal and hepatic events is higher with a 40 mg dose.

Orally. Dosage should be determined individually, in accordance with current recommendations, depending on the purpose of therapy and patient's response to treatment. Before and during treatment, the patient should use a diet to reduce cholesterol.Treatment of hypercholesterolemia: initially 5-10 mg once daily, both in patients who have not been previously treated with other statin drugs, as well as in those treated with other HMG-CoA reductase inhibitors. If necessary, the dose may be increased after 4 weeks of treatment. Due to the increased incidence of side effects after administration of the 40 mg dose, this dose may only be considered in patients with severe hypercholesterolemia who are at high risk of developing cardiovascular disease (particularly those with familial hypercholesterolaemia) who have failed to achieve the intended treatment goal after 20 mg. Treatment with a 40 mg dose should be carried out under the supervision of a specialist.Prevention of cardiovascular events20 mg daily.Children. The use of the drug in children should be carried out by a specialist. Children and adolescents aged 10 to 17 years (boys in phase II and following according to Tanner scale and girls at least one year after the first menstrual period): initial dose 5 mg once a day; a range of usual doses of 5-20 mg once a day; the efficacy and safety of doses> 20 mg in this age group has not been studied; do not use a 40 mg dose. The drug is not recommended for use in children <10 years.Special groups of patients. In the elderly (> 70 years), in patients with moderate renal impairment (creatinine clearance <60 ml / min), in patients with predisposing factors for myopathy and Asian patients, the recommended starting dose is 5 mg.Way of giving. The preparation can be taken at any time of the day, with or without food.