Treatment of hypercholesterolemia. In adults, adolescents and children aged ≥10 years or older with primary hypercholesterolaemia (type IIa, including heterozygous familial hypercholesterolaemia) or mixed dyslipidemia (type IIb) as an add-on to the diet when the response to diet or other non-pharmacological treatments (eg physical exercise, weight loss) is insufficient. In patients with familial homozygous hypercholesterolaemia as a dietary supplement or other type of lipid-lowering therapy (eg LDL apheresis) or where such treatment is inappropriate.Prevention of cardiovascular events: in patients who are at high risk for the first cardiovascular event, in addition to the correction of other risk factors.
Composition:
1 tabl powl. contains 5 mg, 10 mg or 20 mg of Rosuvastatin in the form of a Calcium salt. The preparation contains lactose. Table. 5 mg contain sunset yellow. Table. 10 mg, 20 mg contain azorubine (aluminum lake).
Action:
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 Cmax 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. T0,5 in the elimination phase, it is about 19 hours.
Contraindications:
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.
Precautions:
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. Very rare reports of immune-mediated necrotic myopathy have been reported, which are clinically characterized by permanent weakness of the proximal muscles and elevated CK levels during treatment or after discontinuation of rosuvastatin; additionally, neuromuscular and serological examinations may be necessary; treatment with immunosuppressants may be required. 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. 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 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. The drug (all doses) contains lactose and should not be used in patients with rare hereditary problems of galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose. Table. 5 mg contain sunset yellow, and tabl. 10 mg and 20 mg contain azorubine - both substances can cause allergic reactions.
Pregnancy and lactation:
Use during pregnancy and breast-feeding is contraindicated. Patients of childbearing age should use effective methods of contraception.
Side effects:
Common: diabetes (mainly in patients whose fasting glucose is ≥5,6 mmol / l, BMI> 30 kg / m2, increased triglycerides, history of hypertension), headache, dizziness, constipation, nausea, abdominal pain, muscle pain, asthenia. Uncommon: pruritus, rash, urticaria. Rare: thrombocytopenia, hypersensitivity reactions (including angioneurotic edema), pancreatitis, increased hepatic transaminases, myopathy and rhabdomyolysis. Very rare: polyneuropathy, memory loss, jaundice, hepatitis, joint pain, hematuria, gynecomastia. Frequency unknown: depression, sleep disorders (including insomnia and nightmares), cough, dyspnoea, diarrhea, Stevens-Johnson syndrome, edema. Rosacea has been observed in rosuvastatin-treated patients (mainly of tubular origin, particularly in patients treated with high doses, and no evidence of proteinuria prior to the onset of acute or progressive kidney disease); increase in creatine kinase activity. Some statins also reported sexual dysfunction, interstitial lung disease (especially during long-term use), tendon dysfunction, sometimes with complications due to rupture. The incidence of rhabdomyolysis, severe adverse reactions from the kidneys and liver is higher after a dose of 40 mg.
Dosage:
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. Initially 5-10 mg once a day, 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.Children. The use of the drug in children should be carried out by a specialist. Children and adolescents from 10 to 17 years of age (boys in phase II and following according to the Tanner scale and girls at least one year after the first menstruation): for children and adolescents with familial heterozygous hypercholesterolemia, the usual recommended starting dose is 5 mg once a day. Dose adjustment should be carried out gradually depending on the individual response and tolerance of the patient to treatment as recommended by the pediatric treatment. The range of usual doses is 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.