Description
Release form
film-coated tablets
Pharmacological action of
Rosuvastatin is a selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, a precursor of cholesterol. The main target of the action of rosuvastatin is the liver, where the synthesis of cholesterol (Ch) and the catabolism of low-density lipoprotein cholesterol (Ch-LDL) are carried out.
Rosuvastatin increases the number of LDL-C receptors on the surface of liver cells, increasing the uptake and catabolism of LDL-C, which in turn leads to the inhibition of very low density lipoprotein cholesterol synthesis (X-VLDL), thereby reducing the total amount of LDL-C and LDL. -LPONP.
Rosuvastatin reduces elevated concentrations of LDL-C, total cholesterol, triglycerides (TG), increases the concentration of high-density lipoprotein cholesterol (Chs-HDL), and also reduces the concentration of apolipoprotein B (ApoV), high-density non-lipoprotein cholesterol (Chs-not HDL), Chs-VLDL, TG and increases the concentration of apolipoprotein A I (ApoA-I), reduces the ratio of Xs-LDL / Xs-HDL, total cholesterol / Xs-HDL and Xs-non-LDL / Xs-HDL, and the ratio of apoV / apoA-I.
The therapeutic effect develops within one week after the start of rosuvastatin 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 regular use of the drug.
Rosuvastatin is effective in adult patients with hypercholesterolemia, with or without hypertriglyceridemia, including in patients with diabetes mellitus and familial hypercholesterolemia.
The additive effect is observed in combination with fenofibrate (in relation to the concentration of TG) and with nicotinic acid in lipid lowering doses (in relation to the concentration of HDL-C), however, the possibility of such combinations should be evaluated by the attending physician taking into account possible risks
Indications
– Primary hypercholesterolemia according to the classification of Fredrickson (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet, when the diet and other non-drug methods of treatment, for example, physical mass reduction) inadequate
– familial homozygous hypercholesterolemia as a supplement to diet and other lipid-containing therapy (e.g., LDL apheresis), or in cases where such therapy is not available
– hypertriglyceridemia (type IV according to the Fredrickson classification) as an addition to the
diet – to slow the progression of atherosclerosis as an addition to the diet in patients, is remarkably effective which shows therapy to reduce the concentration of total Chs and Chs-LDL
– the primary prevention of major cardiovascular complications (stroke, myocardial infarction, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), but with an increased risk of its development ( age over 50 for men and over 60 for women, increased concentration of C-reactive protein (more than 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low the concentration of HDL-C, smoking, a family history of the early onset of coronary heart disease).
Use during pregnancy and lactation
Rosuvastatin is contraindicated in pregnancy and lactation.
Women of reproductive age should use adequate methods of contraception.
Since XC and substances synthesized from Xc are important for fetal development, the potential risk of inhibition of HMG-CoA reductase in the fetus outweighs the benefits of rosuvastatin during pregnancy.
In case of pregnancy during treatment, the use of 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 stopped.
FDA category of action on the fetus is X.
Special instructions
Impaired renal function. In patients receiving high doses of rosuvastatin (in particular 40 mg / day), tubular proteinuria was observed, which was detected using test strips and in most cases was periodic or short-term. Such proteinuria does not indicate an acute disease or progression of concomitant kidney disease. The frequency of serious renal impairment noted in the post-marketing study of rosuvastatin is higher with a dose of 40 mg / day. In patients taking the drug at a dose of 30 or 40 mg / day, it is recommended to monitor renal function indicators during treatment (at least 1 time in 3 months).
Influence on the musculoskeletal system. When using rosuvastatin in all doses, but especially in doses exceeding 20 mg / day, the following effects on the musculoskeletal system were reported: myalgia, myopathy, in rare cases, rhabdomyolysis. Very rare cases of rhabdomyolysis were noted with the simultaneous use of HMG-CoA reductase and ezetimibe inhibitors. This combination should be used with caution, as pharmacodynamic interaction cannot be ruled out. As with other HMG-CoA reductase inhibitors, the frequency of rhabdomyolysis in the post-marketing use of rosuvastatin is higher with a dose of 40 mg / day.
Determination of CPK activity. The activity of CPK cannot be determined after intense physical exertion, and if there are other possible reasons for increasing its activity, this can lead to an incorrect interpretation of the results. If the initial activity of CPK is significantly exceeded (5 times higher than VGN), after 5-7 days, a second analysis should be carried out. Do not start therapy if the results of the repeated analysis confirm the initial high activity of CPK (more than 5-fold excess of VGN).
Before starting
therapy Depending on the daily dose in patients with existing risk factors for myopathy / rhabdomyolysis, rosuvastatin is either contraindicated or should be prescribed with caution (see “Contraindications”, “Restrictions on use”).
These factors include: impaired renal function hypothyroidism of a muscle disease in the history (including family history) of myotoxic effects when taking other HMG-CoA reductase inhibitors or fibrates in history of excessive alcohol consumption over the age of 65 years, a condition in which increased plasma concentration of rosuvastatin in the simultaneous use of fibrates.
In these patients, the risk and potential benefits of therapy should be assessed. Clinical monitoring is also recommended. If the initial activity of CPK is more than 5 times higher than that of VGN, rosuvastatin therapy cannot be started.
During treatment with rosuvastatin
, the patient should be informed of the need to immediately consult a doctor in case of sudden onset of muscle pain, muscle weakness or cramping, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if the activity of CPK is significantly increased (more than 5 times compared with VGN) or the symptoms of the muscles are pronounced and cause daily discomfort (even if the activity of KFK is not more than 5 times higher than VGN). If symptoms disappear and CPK activity returns to normal, consideration should be given to resuming the use of rosuvastatin or other HMG-CoA reductase inhibitors in lower doses with careful medical supervision. Monitoring the activity of CPK in the absence of symptoms is impractical.
Very rare cases of immune-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of the proximal muscles and increased CPK activity in the blood serum during therapy or when stopping the use of HMG-CoA reductase inhibitors, including rosuvastatin. Additional studies of the muscle and nervous system, serological studies, as well as immunosuppressive therapy may be required.
No evidence of increased effects on skeletal muscle when taking rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy was reported in patients taking other HMG-CoA reductase inhibitors in combination with fibroic acid derivatives (e.g. gemfibrozil), cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), antifungal derivatives azole, HIV protease inhibitors and macrolide antibiotics.
When used with certain HMG-CoA reductase inhibitors, gemfibrozil increases the risk of myopathy. Thus, the simultaneous use of rosuvastatin and gemfibrozil is not recommended. The benefits of further changing the plasma concentration of lipids with the combined use of this drug with fibrates or nicotinic acid in lipid lowering doses should be carefully weighed taking into account the possible risk. 30 mg / day rosuvastatin is contraindicated for combination therapy with fibrates.
Due to the increased risk of rhabdomyolysis, rosuvastatin should not be used in patients with acute conditions that can lead to myopathy, or conditions predisposing to the development of renal failure (e.g. sepsis, arterial hypotension, extensive surgery, trauma, severe metabolic, endocrine and electrolyte disturbances or uncontrolled convulsions).
Liver. Depending on the daily dose, rosuvastatin is contraindicated or should be used with caution in patients with excessive alcohol consumption and / or with a history of liver disease (see “Contraindications”, “Restrictions on the use”). It is recommended to determine the functional samples of the liver before starting therapy and 3 months after its start. The use of rosuvastatin should be discontinued or the dose of this agent should be reduced if the activity of hepatic transaminases in the blood serum is 3 times higher than VGN.
In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy of the underlying diseases should be performed before treatment with rosuvastatin.
Ethnic features. During pharmacokinetic studies in representatives of the Mongoloid race, compared with representatives of the Caucasian race, an increase in the plasma concentration of rosuvastatin was noted.
Interstitial lung disease. When using certain inhibitors of HMG-CoA reductase, especially for a long time, isolated cases of interstitial lung disease have been reported. Manifestations of the disease can include shortness of breath, unproductive cough, and general well-being (weakness, weight loss, and fever). If interstitial lung disease is suspected, therapy with HMG-CoA reductase inhibitors should be discontinued.
Type 2 diabetes mellitus. In patients with a glucose concentration of 5.6 to 6.9 mmol / L, rosuvastatin therapy was associated with an increased risk of type 2 diabetes mellitus.
Effect on the ability to drive a car or perform work requiring an increased physical and mental speed reactions. Studies to study the effect of rosuvastatin on the ability to drive vehicles and work with mechanisms have not been conducted. Nonetheless, Considering the possibility of developing dizziness and other side effects, caution must be exercised when driving vehicles and other mechanisms that require an increased concentration of attention and speed of psychomotor reactions.
Composition
active ingredient:
rosuvastatin calcium – 10.4 mg (in terms of rosuvastatin – 10.0 mg)
excipients:
lactose monohydrate – 109.8 mg,
microcrystalline cellulose, 36.0 mg
calcium hydrogen phosphate dihydrate – 13.0 mg,
crospovidone – 9.0 mg,
magnesium stearate – 1.8 mg
film coat:
[hypromellose – 3.2400 mg, talc – 1.0800 mg, titanium dioxide – 0 , 5724 mg, macrogol 4000 (polyethylene glycol 4000) – 0.4860 mg, red iron oxide (iron oxide) – 0.0216 mg] or [dry film coating mixture containing hypromellose (60%), talc (20%), titanium dioxide (10.6%), macrogol 4000 (polyethylene glycol 4000) (9%), iron oxide red (iron oxide) (0.4%)] – 5.4000 mg
Dosage and administration
Inside, do not chew or grind the tablet, swallow whole, washed down with water. The drug can be prescribed at any time of the day, regardless of the time of meal.
Before starting therapy with Rosuvastatin, 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 current recommendations on target lipid concentrations.
Recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 or 10 mg of the drug Rosuvastatin 1 time / day. When choosing an initial dose, one should be guided by the individual cholesterol content and take into account the possible risk of cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, the dose can be increased to a greater value after 4 weeks
Due to the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug (see section Side effects), increase the dose to 40 mg, after an additional taking a dose higher than the recommended starting dose for 4 weeks of therapy, can be performed only in patients with severe hypercholesterolemia and with a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who have not achieved the desired result of therapy when taking a dose of 20 mg, and who will be under the supervision of a specialist. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.
Dosage of 40 mg is not recommended for patients who have not previously consulted a doctor.
After 2-4 weeks of therapy and / or with an increase in the dose of Rosuvastatin, monitoring of lipid metabolism is necessary (dose adjustment is necessary if necessary). The use of the drug in a higher dose than 40 mg is not justified in connection with the increase in side effects and in most cases is not recommended.
Elderly
patients No dose adjustment is required.
Patients with Renal Insufficiency
Dose adjustment is not required in patients with renal insufficiency of mild or moderate severity. In patients with severe renal failure (CC less than 30 ml / min.), The use of the drug Rosuvastatin is contraindicated. The use of the drug at a dose of 40 mg is contraindicated in patients with moderate impaired renal function (CC 30-60 ml / min). For patients with moderate impaired renal function, an initial dose of 5 mg is recommended.
Patients with liver failure
Rosuvastatin is contraindicated in patients with active liver disease
Special populations. Ethnic groups
When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in systemic concentration of rosuvastatin among Japanese and Chinese was noted (see Special Instructions). This fact should be taken into account when prescribing Rosuvastatin to these patient groups. When prescribing doses of 10 and 20 mg, the recommended initial dose for patients of the Mongoloid race is 5 mg. Administration of the drug in a dose of 40 mg is contraindicated for patients of the Mongoloid race (see section Contraindications).
Genetic polymorphism
In carriers of genotypes SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) s.421AA, an increase in exposure (AUC) to rosuvastatin was noted compared to carriers of genotypes SLCO1B1 c.521TT and ABCG2 c.421. For patients carrying genotypes c.521CC or s.421AA, the recommended maximum dose of Rosuvastatin is 20 mg 1 time / day.
patients, predisposition to myopathy
Administration of the drug in a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy. When prescribing doses of 10 and 20 mg, the recommended starting dose for this group of patients is 5 mg
Concomitant therapy with
Rosuvastatin binds to various transport proteins (in particular, OATP1B1 and BCRP).
When combined with rosuvastatin and drugs (such as cyclosporine, some HIV protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and / or tipranavir), which increase the concentration of rosuvastatin in plasma due to interaction with transport proteins, the risk of myopathy (including rhabdomyolysis) may increase
In such cases, the possibility of prescribing alternative therapy or temporarily stopping the use of Rosuvastatin should be evaluated. If the use of the above drugs is necessary, it is necessary to assess the ratio of the benefit and risk of concomitant therapy with Rosuvastatin and consider reducing its dose
Side effects
Side effects observed with rosuvastatin, usually expressed slightly and pass on their own. As with other HMG-CoA reductase inhibitors, the incidence of side effects is primarily dose-dependent.
Classification of the incidence of side effects WHO: very often (? 1/10) often (? 1/100,
from the blood and lymphatic system: unknown frequency – thrombocytopenia.
from the immune system: rarely – hypersensitivity reactions, including angioedema edema
On the part of the endocrine system: often type 2 diabetes mellitus
On the part of the nervous system: often headache, dizziness is very rare – loss or decrease in memory frequency is unknown – peripheral neuropathy
On the part of the respiratory system we, chest and mediastinal organs: frequency is unknown – cough, shortness of breath.
From the digestive system: often – constipation, nausea, abdominal pain is rare – pancreatitis is very rare – jaundice, hepatitis, frequency is unknown – diarrhea.
When using rosuvastatin, a dose-dependent increase in the activity of hepatic transaminases in blood plasma is observed in a small number of patients. In most cases, it is insignificant, asymptomatic and temporary.
From the skin and subcutaneous tissues: infrequently – skin itching, skin rash, urticaria, frequency unknown – Stevens-Johnson syndrome.
From the side of the musculoskeletal system and connective tissue: often – myalgia rarely – myopathy (including myositis), rhabdomyolysis (with or without acute renal failure) very rarely – arthralgia frequency is unknown – immune-mediated necrotizing myopathy.
A dose-dependent increase in plasma KFK activity is observed in a small number of patients taking rosuvastatin. In most cases, it is mild, asymptomatic and temporary. In the case of increased CPK activity in blood plasma more than 5 times higher than VGN, therapy should be suspended.
From the kidneys and urinary tract: proteinuria may be detected in patients receiving rosuvastatin therapy. A change in the amount of protein in the urine (from the absence or trace amounts to ++ or more) is observed in less than 1% of patients receiving 10 20 mg of rosuvastatin, and in about 3% of patients receiving a dose of 40 mg / day. A slight change in the amount of protein in the urine was observed when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or progression of an existing kidney disease, very rarely – hematuria.
From the genitals and mammary gland: frequency unknown – gynecomastia.
General disorders and disorders at the injection site: often – asthenic syndrome, frequency unknown – peripheral edema.
Laboratory indicators: hyperglycemia, increased plasma bilirubin concentration, GGTP activity, alkaline phosphatase in blood plasma, changes in serum thyroid hormone concentration.
The following side effects have been reported with certain HMG-CoA reductase inhibitors (statins): depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction, increased concentration of glycosylated hemoglobin. Isolated cases of interstitial lung disease have been reported, especially with prolonged use of these drugs
Drug interactions
Transport protein inhibitors: rosuvastatin binds to certain transport proteins, in particular, OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins, may be accompanied by an increase in plasma concentration of rosuvastatin and an increased risk of myopathy.
Cyclosporine: with the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than that observed in healthy volunteers. Rosuvastatin does not affect the plasma concentration of cyclosporine. Rosuvastatin is contraindicated in patients taking cyclosporine.
Human immunodeficiency virus (HIV) protease inhibitors: although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors and rosuvastatin can lead to a significant increase in AUC of rosuvastatin. A pharmacokinetic study but the simultaneous use of 20 mg of rosuvastatin with a combination drug, containing two HIV
protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers led to an increase in AUC (0-24) and Cmax of rosuvastatin by approximately 2 and 5 times, respectively. Therefore, the simultaneous administration of rosuvastatin and HIV protease inhibitors is not recommended.
Gemfibrozil and other lipid-lowering drugs: the combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax in blood plasma and AUC of rosuvastatin (see section Special instructions).
Based on data on specific interactions, pharmacokinetically significant interactions with fenofibrate are not expected, pharmacodynamic interactions are possible. Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g / day) increased the risk of myopathy when used with HMG-CoA reductase inhibitors, possibly due to the fact that they can also cause myopathy when used as monotherapy (see section Special instructions ). With the simultaneous administration of the drug Rosuvastatin with gemfibrozil, fibrates, nicotinic acid in lipid lowering doses (more than 1 g / day), patients are recommended an initial dose of 5 mg, a dose of 40 mg is contraindicated in conjunction with fibrates.
Ezetimibe: simultaneous use of rosuvastatin at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in AUC of rosuvastatin in patients with hypercholesterolemia (see table). It is impossible to exclude an increased risk of side effects due to the pharmacodynamic interaction between the drug Rosuvastatin and ezetimibe.
Antacids: The simultaneous use of rosuvastatin and suspensions of antacids containing aluminum and magnesium hydroxide, reduces the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.
Erythromycin: simultaneous use of rosuvastatin and erythromycin leads to a decrease in AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. Such an interaction can occur as a result of increased intestinal motility caused by taking erythromycin.
Isoenzymes of the cytochrome P450 system: the results of in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of isoenzymes of the cytochrome P450 system. KrIn addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, the interaction of rosuvastatin with other drugs at the metabolic level with the participation of isoenzymes of the cytochrome P450 system is not expected. There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of isoenzymes CYP2C9 and CYP3A4) and ketoconazole (an inhibitor of isoenzymes CYP2A6 and CYP3A4).
Fusidic acid: no studies have been conducted to study the interaction of rosuvastatin and fusidic acid. As with other statins, post-marketing reports of rhabdomyolysis with co-administration of rosuvastatin and fusidic acid were received. It is necessary to carefully monitor patients. If necessary, a temporary discontinuation of the drug Rosuvastatin is possible.
Storage conditions
Store in a dark place at a temperature not exceeding 25 ° C.
Keep out of the reach and sight of children.
Term hodnosty
2 years
active substance
Rosuvastatin
lekarstvennaja form
tablets
