Index of drugs

Hypercholesterolemia treatmenti. Primary hypercholesterolemia in adults, adolescents and children aged 10 years and older (type IIa, including familial heterozygous hypercholesterolemia) or mixed dyslipidemia (type IIb) as an add-on to the diet when using diet and other non-pharmacological treatments (e.g. physical exercise, weight loss) is insufficient. Familial homozygous hypercholesterolemia as an add-on to diet and other lipid-lowering treatments (eg LDL apheresis) or if other treatments are inappropriate.Prevention of cardiovascular events. Prevention of major cardiovascular events in patients at high risk of this event for the first time, together with activities aimed at reducing 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. The preparation contains: lactose, sunset yellow, tartrazidine, lak. In addition, tabl. 10 mg, 20 mg and 40 mg contain: red Allura AC, lak.

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that limits the rate of conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor to cholesterol. It 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, which leads to a reduction in the total amount of LDL and VLDL. After oral administration, rosuvastatin reaches C_max in plasma after about 5 hours. Absolute bioavailability is about 20%. Rosuvastatin binds to plasma proteins, mainly to albumin, in approximately 90%. It is metabolized to a small extent (10%). Approx. 90% of rosuvastatin is excreted unchanged with faeces (both absorbed and unabsorbed). The remaining part is excreted in urine, approx. 5% in unchanged form. T_0,5 in the phase of elimination is about 19 h. Acquiring rosuvastatin by liver cells is carried out by OATP-C - a transport compound in the membrane of the liver cell.

Hypersensitivity to rosuvastatin or any of the excipients. Active liver disease, including unexplained persistently elevated serum transaminases 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 use of cyclosporin. Pregnancy, breastfeeding period. Women of childbearing potential not using effective methods of preventing pregnancy. The 40 mg dose is contraindicated in patients with predisposing factors for myopathy or rhabdomyolysis. These include moderate renal impairment (creatinine clearance <60 ml / min), hypothyroidism, genetically determined muscular disease in a patient or members of his or her 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, origin in Asia, concomitant use of medicines from the group of fibrates.

Due to the risk of proteinuria in patients treated with a 40 mg dose, renal function should be considered during routine inspections. If creatine kinase (CK) activity is significantly increased before treatment (> 5 x ULN), follow-up should be performed after 5-7 days; treatment should not be started if CK> 5 x ULN is in a control test. The preparation should be used with caution in patients with predisposing factors for myopathy or rhabdomyolysis: 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 the concentration of an active substance in the serum may increase, simultaneous use of drugs from the group of fibrates.In this group of patients, the risk and possible benefits of treatment should be considered and the patient should be monitored during treatment. If unexplained muscle aches, muscular weakness or muscle cramps occur, especially if you feel unwell or have a fever, you should have a CK activity test. If the CK activity is significantly increased (> 5 x ULN) or if the muscle symptoms are severe and cause problems in everyday activities (even if CK ≤5 x ULN), treatment should be discontinued. After the clinical symptoms have resolved and CK levels are reduced to normal, re-application of the formulation or other HMG-CoA reductase inhibitor at the lowest dose may be considered. The patient should remain under strict control. If the patient does not have clinical symptoms, routine CK activity monitoring is not necessary. During admission or after completion of statins, including Rosuvastatin, necrotic myelopathy (IMNM) has been reported very rarely, which is characterized by a weakening of the proximal muscles and an increase in serum CK activity that persists despite discontinuation of statin therapy. Do not use the product if you have severe, severe symptoms that may indicate myopathy or predispose to secondary renal failure as a result of rhabdomyolysis (eg sepsis, hypotension, extensive surgery, trauma, severe metabolic disorders, endocrine and electrolyte or uncontrolled epilepsy) ). 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. Treatment should be discontinued or the dose reduced if serum aminotransferases are more than 3-fold higher than ULN. The incidence of serious liver side effects is higher at a dose of 40 mg. In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, appropriate treatment of the underlying disease should be initiated prior to treatment initiation. Pharmacokinetic studies have shown increased drug exposure in patients from Asia compared to the Caucasians. In case of suspected interstitial pneumonitis, statin therapy should be discontinued. Statins increase blood Glucose levels and in some patients at high risk of future diabetes, they can cause hyperglycaemia with severity requiring appropriate diabetes care. This risk is however outweighed by the benefit of reducing the risk of developing vascular disease, so statin therapy should not be discontinued. Patients at risk (patients with fasting glucose 5,6-6,9 mmol / l, BMI> 30 kg / m², with increased triglycerides, hypertension) should be subjected to clinical and biochemical monitoring in accordance with the guidelines. In patients with hepatic impairment with 8 or 9 Child-Pugh score, increases in systemic exposure to rosuvastatin have been observed (renal function should be considered in these patients); no data on the use of the drug in patients from the group of more than 9 points on the Child-Pugh scale. The experience of using the drug in children under 10 years is limited to a small number of children (8-10 years) with homozygous familial hypercholesterolaemia. The drug is not recommended for use in children under 10 years. The assessment of body mass growth, BMI index and maturity of secondary sexual characteristics according to Tanner scale in children of 10-17 years using rosuvastatin is limited to 1 year - no effect on height, body mass, BMI index or sexual maturity was detected. The use experience in children and adolescents is limited, and the long-term effect of the drug (> 1 year) on puberty is unknown. In clinical studies in children and adolescents receiving rosuvastatin for 52 weeks, an increase in creatinine kinase> 10 x ULN and muscle symptoms following exercise or increased physical activity were observed more frequently compared to those observed in adult clinical trials. Table. 40 mg are not intended for use in pediatric patients.The preparation contains lactose - should not be used in patients with rare hereditary galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose. The preparation contains azo dyes - sunset yellow and tartrazidine (all doses) and Allura red (table 10 mg, table 20 mg and table 40 mg), which may cause allergic reactions.

Use during pregnancy and breast-feeding is contraindicated. Patients of childbearing age should use effective methods of contraception. If during pregnancy the patient becomes pregnant, treatment should be stopped immediately.

Common: diabetes (frequency depends on risk factors: fasting glucose level ≥5,6 mmol / l, BMI> 30 kg / m², increased triglycerides in the blood, hypertension in history), headache and dizziness, constipation, nausea, abdominal pain, muscle pain, weakness. Uncommon: pruritus, rash, urticaria. Rare: thrombocytopenia, hypersensitivity reactions (including angioneurotic edema), pancreatitis, increased liver aminotransferases, myopathy (including myositis), rhabdomyolysis (with or without acute renal failure). Very rare: polyneuropathy, impaired memory, jaundice, hepatitis, arthralgia, hematuria, gynecomastia. Not known: depression, peripheral neuropathy, sleep disorders (including insomnia and nightmares), cough, dyspnea, diarrhea, Stevens-Johnson syndrome, immunoreceptor myelopathy, swelling. Rosacea has been observed in patients treated with rosuvastatin, mainly of tubular origin. In most cases, proteinuria decreases or disappears during treatment. Data from clinical trials and post-marketing experience did not show that proteinuria preceded the onset of acute or progressive kidney disease. Haematuria has been observed in rosuvastatin-treated patients, but clinical data indicate that its frequency is low. Rosuvastatin-treated patients have a dose dependent increase in the creatine kinase activity; in most cases it was mild, asymptomatic and transient; if creatine kinase (> 5 x ULN) is increased, treatment should be discontinued. The following side effects have been seen with some statins: sexual dysfunction; interstitial pneumonia especially during long-term therapy (isolated cases), tendon diseases, sometimes complicated by rupture. The incidence of rhabdomyolysis, severe renal and hepatic adverse reactions (mainly elevation of transaminases) is higher after a dose of 40 mg.

Orally. Dosage should be determined individually, in accordance with current recommendations depending on the purpose of therapy and patient's response to treatment.Treatment of hypercholesterolemiaThe recommended starting dose is 5 mg or 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. The cholesterol concentration, risk factors for cardiovascular disease, as well as the risk of side effects should be considered for each patient when determining the starting dose. If necessary, the dose may be increased after 4 weeks of treatment. Due to the increased incidence of adverse reactions after a 40 mg dose compared to the use of lower doses, increasing the dose up to a maximum dose of 40 mg can only be considered in patients with severe hypercholesterolaemia who are at high risk of cardiovascular disease (particularly those with familial hypercholesterolemia) in which the expected goal of therapy was not obtained after the 20 mg dose. Patients treated with 40 mg should remain under routine control. It is recommended that the introduction of a 40 mg dose should be under the control of a specialist.Prevention of cardiovascular events20 mg daily.Children and youth 10-17 years (boys in phase II and following according to Tanner scale, girls at least one year after the first menstruation) - only tabl. 5 mg, 10 mg and 20 mg, treatment should be carried out by a specialist doctor. In pediatric patients with heterozygous familial hypercholesterolaemia, the usual starting dose is 5 mg daily; the usual dose range is 5-20 mg once a day.Dose escalation should be based on individual response and tolerance to treatment. The efficacy and safety of doses greater than 20 mg in this age group has not been studied. In elderly patients (> 70 years), in patients with moderate renal insufficiency (creatinine clearance <60 ml / min), in patients of Asian origin and in patients with risk factors for myopathy, the recommended starting dose is 5 mg. Patients with a genetic polymorphism that may lead to increased rosuvastatin exposure are advised to use a lower daily dose of rosuvastatin. Rosuvastatin is a substrate for various transporting proteins (e.g., OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when rosuvastatin is given concurrently with certain drugs that may increase the plasma concentration of rosuvastatin due to the interaction with these transport proteins (eg with cyclosporin and some protease inhibitors, including the combination of ritonavir and atazanavir, The use of alternative medicines and, if necessary, timely treatment with rosuvastatin should be considered wherever possible, and when it is unavoidable to use these medicines concomitantly with rosuvastatin, consideration should be given to the benefits and risks of rosuvastatin. dosage adjustment of rosuvastatin and parallel therapy.
The preparation can be taken at any time of the day, regardless of meals. Table. 20 mg and tabl. 40 mg can be divided into two equal doses.