Index of drugs

Primary hypercholesterolaemia or mixed dyslipidemia (type IIb) as an additional treatment to the diet when the use of diet and other non-pharmacological treatments (eg 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 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.

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 (about 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 the active substance or to 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; 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 HMGCoA 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. Due to the risk of rhabdomyolysis (very rare cases), caution should be used when using ezetimibe. If creatine kinase (CK) activity is markedly increased (> 5 x ULN) before starting treatment, treatment should not be started. 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. In patients concomitantly treated with other HMG-CoA reductase inhibitors, fibric acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid, azoles, protease inhibitors or macrolide antibiotics, an increased incidence of myositis and myopathy has been reported. Co-administration of the preparation and gemfibrozil is not recommended. The benefits of changing lipids and the risks associated with the use of fibrates or nicotinic acid and the combination should be carefully weighed down. Do not use the product if you have severe, severe symptoms that may indicate myopathy or predisposition to secondary renal failure due to rhabdomyolysis (eg sepsis, hypotension, extensive surgery, trauma, severe metabolic disorders, endocrine and electrolyte or uncontrolled epilepsy) ). The preparation 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. Co-administration of rosuvastatin with protease inhibitors is not recommended. In case of suspected interstitial pneumonitis, statin therapy should be discontinued. Statins increase blood sugar levels, and in some patients at risk of developing diabetes, they can cause hyperglycaemia, which should be treated according to official recommendations. However, the above-mentioned risk has the advantage of reducing the risk of vascular complications in statin users and therefore it should not result in discontinuation of statin therapy. Patients at risk (fasting blood sugar 5.6-6.9 mmol / L, BMI> 30 kg / m², increased levels of triglycerides in the blood, hypertension in history) should be subjected to both clinical and biochemical diagnostics in accordance with national guidelines. In patients with hepatic impairment with 8 or 9 Child-Pugh score, an increase in rosuvastatin exposure was observed; no data on use in patients from the group of more than 9 points on the Child-Pugh scale. Rosuvastatin is not recommended for use in children and adolescents under 18 due to the lack of data on the safety and efficacy of this medicine in this group. The experience of using the drug in children is limited to a small number of patients (aged 8 years or older) with familial homozygous hypercholesterolemia. 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 product contains quinoline yellow, 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 blood sugar level ≥5,6 mmol / l, BMI> 30 kg / m², increased levels of triglycerides in the blood, hypertension in history), headache and dizziness, nausea constipation, abdominal pain, muscle pain, weakness. Uncommon: pruritus, redness, hives.Rare: hypersensitivity reactions (including angioneurotic edema), pancreatitis, myopathy (including myositis), rhabdomyolysis. Very rare: gynecomastia. Rosacea has been observed in patients treated with Rosuvastatin, mainly of tubular origin. In most cases, proteinuria decreases or disappears during treatment. No proteinuria was found to precede the onset of acute or progressive kidney disease. Haematuria has been observed in patients treated with rosuvastatin (the incidence is low). The incidence of rhabdomyolysis, severe renal and hepatic adverse reactions (mainly elevation of transaminases) is higher after a dose of 40 mg. There have been rare reports of post-marketing experience: elevation of hepatic transaminases; very rare: polyneuropathy, memory loss, jaundice, hepatitis, arthralgia, hematuria; frequency unknown: cough, dyspnoea, diarrhea, Stevens-Johnson syndrome, edema. Adverse reactions observed with some statins: depression, sleep disorders (including insomnia and nightmares), sexual dysfunction, in exceptional cases, interstitial pneumonia, especially during long-term therapy.

Orally. Adults. Dosage should be determined individually, in accordance with current recommendations depending on the purpose of therapy and patient's response to treatment.Treatment of hypercholesterolemia. The recommended starting dose is 5-10 mg once a day, both in patients who have not previously been 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. The maximum daily dose is 40 mg. Increasing the dose to 40 mg can only be considered in patients with severe hypercholesterolaemia who are at high risk of developing cardiovascular disease (particularly those with familial hypercholesterolaemia) who have failed to achieve the intended treatment target after 20 mg. 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 events. A dose of 20 mg per day was used in the studies.
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 predisposing factors for myopathy, the recommended starting dose is 5 mg. The preparation can be taken at any time of the day, regardless of meals.