Description
film-coated
film-coated tablets
Packing
90 pcs.
Pharmacological action
Roxer drug – lipid-lowering agent.
The active ingredient of the drug, rosuvastatin, is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, the precursor of cholesterol.
The main target of the action of rosuvastatin is the liver, where cholesterol (cholesterol) synthesis and LDL catabolism occur.
Increases the number of hepatic LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of VLDL synthesis, thereby reducing the total amount of LDL and VLDL.
Rosuvastatin reduces elevated plasma concentrations of LDL cholesterol (LDL-C), total cholesterol, triglycerides (TG), and increases the concentration of high-density lipoprotein cholesterol (HDL-C).
It also reduces the concentration of apolipoprotein B (ApoB), cholesterol-free cholesterol, cholesterol-VLDL, TG-VLDL and increases the concentration of apolipoprotein AI (Apo A-1) in blood plasma.
Rosuvastatin reduces the ratio of cholesterol-LDL / cholesterol-HDL, total cholesterol / cholesterol-HDL and cholesterol-non-HDLP / cholesterol-HDL and the ratio of ApoV / ApoA-1. The therapeutic effect develops within one week after the start of therapy, after 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with continued regular use of the drug.
Indications
primary Fredrickson hypercholesterolemia (type IIa) or mixed dyslipidemia (type IIb) as a supplement to the diet for the ineffectiveness of the diet and other non-drug therapies (e.g. physical activity, weight loss)
familial homozygous hypercholesterolemia as an adjunct to diet and other lipid lowering therapy (e.g. LDL apheresis) or if such therapy is not effective
hypertriglyceridemia (Fredrickson type IV) as an adjunct to the
diet to slow the progression of atherosclerosis in patients who are shown therapy to reduce the plasma concentration of cholesterol and cholesterol-LDL
primary prevention of major cardiovascular complications (stroke, myocardial infarction, arterial revas ulyarizatsiya) in adult patients without clinical evidence of coronary heart disease (CHD), but with an increased risk of its development (age over 50 years for men and over 60 for women, increased plasma concentration of C-reactive protein ( 2 g / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low plasma concentration of HDL-C, smoking, early onset of coronary heart disease in a family history.
Use during pregnancy and lactation
Roxer is contraindicated in pregnancy and lactation.
Women of reproductive age should use adequate methods of contraception.
Since cholesterol and substances synthesized from cholesterol are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase in the fetus outweighs the benefits of the drug during pregnancy.
In case of pregnancy during treatment, the drug should be stopped immediately.
There are no data on the excretion of rosuvastatin with breast milk (it is known that other HMG-CoA reductase inhibitors are excreted in breast milk), therefore, during breastfeeding, the use of the drug must be discontinued.
Composition
Active substance:
Rosuvastatin calcium 20 mg
Excipients:
MCC
Lactose
Crospovidone
Silicon dioxide colloid
Magnesium stearate
Shell Film: butyl methacrylate, dimethylaminoethyl methacrylate copolymer [1: 2: 1] Macrogol 6000 Titanium dioxide lactose monohydrate
Dosage and administration
Inside, do not chew or grind the tablet, swallow whole, washed down with water, can be taken at any time of the day, regardless of food intake.
Before starting therapy with Roxer ®, the patient should start to follow a standard hypocholesterolemic diet and continue to follow it during treatment. The dose of the drug should be selected individually, depending on the goals of therapy and the therapeutic response to treatment, taking into account recommendations on target plasma lipid concentrations.
Recommended starting dose for patients beginners to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 or 10 mg of Roxer ® 1 time per day.
With the simultaneous use of the drug with gemfibrozil, fibrates, nicotinic acid in a dose of more than 1 g / day, patients are recommended an initial dose of 5 mg. When choosing an initial dose, one should be guided by the individual plasma cholesterol concentration and take into account the possible risk of developing cardiovascular complications, it is also necessary to take into account the potential risk of side effects. If necessary, the dose can be increased after 4 weeks.
Due to the possible development of side effects when applying a dose of 40 mg / day, compared with lower doses of the drug, increasing the dose to 40 mg / day after additional use of the dose above the recommended initial dose for 4 weeks of therapy can be carried out only in patients with severe hypercholesterolemia and a high risk of developing cardiovascular complications (especially in patients with familial hypercholesterolemia) the desired result of therapy was achieved with a dose of 20 mg / day and which will be under the supervision of a doctor. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg / day is recommended.
The use of a dose of 40 mg / day in patients who have not previously consulted a doctor is not recommended. After 2 4 weeks of therapy and / or with an increase in the dose of Roxer ®, monitoring of lipid metabolism is necessary (dose adjustment is necessary if necessary).
Patients with renal failure. In patients with mild or moderate renal failure, dose adjustment is not required. In patients with severe renal failure (Cl creatinine less than 30 ml / min), the use of Roxer ® is contraindicated. The use of the drug in a dose of more than 30 mg / day is contraindicated in patients with moderate to severe renal failure (Cl creatinine less than 60 ml / min). For patients with moderate renal failure, the recommended initial dose of the drug is 5 mg / day.
Patients with liver failure. Roxer ® is contraindicated in patients with active liver disease. There is no experience with the use of the drug in patients with liver failure above 9 points (grade C) on the Child-Pugh scale.
Use in elderly patients. Patients over the age of 65 are recommended to start using the drug with a dose of 5 mg / day.
Special populations of
When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in systemic concentration of rosuvastatin was noted among Japanese and Chinese. This fact should be taken into account when using Roxer ® in this group of patients. When applying doses of 10 and 20 mg / day, the recommended initial dose for patients of the Mongoloid race is 5 mg / day. Patients of the Mongoloid race, the use of the drug in a dose of 40 mg is contraindicated.
Patients predisposed to myotoxic complications. The use of the drug in a dose of 40 mg in patients predisposed to the development of myotoxic complications is contraindicated. If it is necessary to use doses of 10 and 20 mg / day, the recommended initial dose for this group of patients is 5 mg. When used with gemfibrozil, the dose of Roxer ® should not exceed 10 mg / day.
Side effects of the
On the part of the immune system: rarely – hypersensitivity reactions, including angioedema.
From the side of the central nervous system: often – headache, dizziness very rarely – polyneuropathy, memory loss.
From the digestive system: often – constipation, nausea, abdominal pain rarely – pancreatitis, increased activity of hepatic transaminases very rarely – jaundice, hepatitis, diarrhea.
From the skin: infrequently – itching, rash, urticaria, very rarely – Stevens-Johnson syndrome.
From the musculoskeletal system and connective tissue: often – myalgia rarely – myopathy (including myositis) and rhabdomyolysis very rarely – arthralgia.
A dose-related increase in creatine phosphokinase (CPK) activity is observed in a small number of patients, taking rosuvastatin. In most cases, it is mild, asymptomatic and temporary. In case of increased activity of CPK more than 5 times higher than VGN, therapy should be suspended.
From the urinary system: often – proteinuria (less than 1% of patients receiving a dose of 10 20 mg / day and about 3% of patients receiving a dose of 40 mg / day). In most cases, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or progressive concomitant kidney disease very rarely – hematuria.
General disorders: often – asthenia.
Laboratory indicators: increased CPK activity, glucose, bilirubin concentration, GGTP, alkaline phosphatase activity, change in plasma concentration of thyroid hormones.
Drug Interaction
Cyclosporine. When rosuvastatin and cyclosporine are co-administered, the AUC of rosuvastatin is on average 7 times higher than that observed in healthy volunteers. The plasma concentration of rosuvastatin is increased 11-fold. Co-administration with rosuvastatin does not affect the concentration of cyclosporine in blood plasma.
Indirect anticoagulants. As with other HMG-CoA reductase inhibitors, initiation of rosuvastatin therapy or increasing its dose in patients receiving concomitant indirect anticoagulants (eg warfarin), may lead to an increase in MHO. The cancellation of rosuvastatin or a decrease in its dose may lead to a decrease in MHO. In such cases, MHO monitoring is recommended.
Ezetimibe. Co-administration of rosuvastatin and ezetimibe is not accompanied by a change in the AUC or Cmax of both drugs. However, the pharmacodynamic interaction between rosuvastatin and ezetimibe, which results in an increased risk of muscle unwanted reactions, cannot be ruled out.
Gemfibrozil and other hypolipidemic agents. Concomitant administration of rosuvastatin and gemfibrozil results in a 2-fold increase in the Cmax and AUC of rosuvastatin. Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid (doses greater than or equivalent to 1 g / day) increased the risk of myopathy when co-administered with HMG-CoA reductase inhibitors (possibly due to the fact that they may cause myopathy and monopathy) . Concomitant use of fibrates and rosuvastatin at a daily dose of 30 mg is contraindicated. In such patients, therapy should be started at a dose of 5 mg / day.
HIV protease inhibitors. Concomitant administration of HIV protease inhibitors can significantly increase the plasma concentration of rosuvastatin. Concomitant administration of 20 mg of rosuvastatin and a combination of two HIV protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir) is accompanied by a 2 and 5 fold increase in equilibrium AUC0-24 and Cmax of rosuvastatin, respectively.
Antacids. Concomitant administration of rosuvastatin and antacids containing aluminum and magnesium hydroxide results in a decrease in the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are administered 2 hours after taking rosuvastatin.
Erythromycin. Concomitant administration of rosuvastatin and erythromycin results in a 20% decrease in the AUC0-t of rosuvastatin and a 30% decrease in its C max. Such interaction may result from increased intestinal motility caused by the use of erythromycin.
Hormonal contraceptives / hormone replacement therapy. Concomitant use of rosuvastatin and hormonal contraceptives increases the AUC of ethinyl estradiol and norgestrel by 26 and 34%, respectively. This increase in blood plasma concentration should be taken into account when selecting a dose of hormonal contraceptives.
There are no pharmacokinetic data on the concomitant use of rosuvastatin and hormone replacement therapy, and therefore, a similar effect cannot be ruled out when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.
Other medicines. No clinically relevant interaction of rosuvastatin with digoxin is expected.
Cytochrome P450 isoenzymes. Rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450. In addition, rosuvastatin is a weak substrate for this isoenzyme system.
No clinically relevant interaction between rosuvastatin and fluconazole (CYP2C9 and CYP3A4 isoenzyme inhibitor) and ketoconazole (CYP2A6 and CYP3A4 isoenzyme inhibitor) was noted. Co-administration of rosuvastatin and itraconazole (an isoenzyme inhibitorCYP3A4) increases rosuvastatin AUC by 28%, which is clinically insignificant. Thus, no interaction is expected with cytochrome P450.
Storage conditions
At a temperature not exceeding 30 ° C.
shelf life
2 years
Active ingredient
Rosuvastatin
dosage form
tablets
Possible product names
ROXER 0.02 N90 TABLE P / O
Roxer 20mg Tab. p / pl / rev X90
ROXER TAB. P.P.O. 20MG No. 90
ROXER TAB. P / O CAPTURE. 20MG No. 90
Roxer table. p.p. about 20mg N90 Slovenia
KRKA d.d. Novo mesto AO, Slovenia
