Description
Pharmacological action of
Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme, converting 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, a cholesterol precursor. The main target of the action of rosuvastatin is the liver, where the synthesis of cholesterol (cholesterol) and the catabolism of low density lipoproteins (LDL) are carried out. Rosuvastatin increases the number of ² Ñliver ² Ñ LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of very low density lipoproteins (VLDL), thereby reducing the total amount of LDL and VLDL.
Pharmacodynamics
Rosuvastatin-SZ reduces elevated concentrations of LDL cholesterol (cholesterol-LDL), total cholesterol, triglycerides (TG), increases the concentration of high-density lipoprotein cholesterol (HDL-cholesterol), and also reduces the concentration of apolipoprotein B -neLPVP, XC-VLDLP, TG-VLDLP and increases the concentration of apolipoprotein A-I (ApoA-I), reduces the ratio of cholesterol-LDL / cholesterol-HDL, total cholesterol-cholesterol-HDL and cholesterol-HDL / cholesterol-HDL and the ratio of apoB / apoA-I. The therapeutic effect develops within one week after the start of therapy with the drug Rosuvastatin-SZ, 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-SZ is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender or age, including patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with type IIa and IIb hypercholesterolemia according to Fredrickson (the average initial concentration of LDL-C is about 4, 8 mmol / L) while taking the drug at a dose of 10 mg, the concentration of LDL-C reaches a value of less than 3 mmol / L. In patients with heterozygous familial hypercholesterolemia, receiving Rosuvastatin-SZ at a dose of 20-80 mg, there is a positive dynamics in the lipid profile. After titration to a daily dose of 40 mg (12 weeks of therapy), a decrease in the concentration of LDL-C by 53% is noted. In 33% of patients, an LDL-C concentration of less than 3 mmol / L is achieved. In patients with homozygous familial hypercholesterolemia, taking Rosuvastatin-SZ at a dose of 20 mg and 40 mg, the average decrease in the concentration of LDL-C is 22%. In patients with hypertriglyceridemia with an initial TG concentration from 273 to 817 mg / dl, treated with Rosuvastatin-SZ at a dose of 5 mg to 40 mg once a day for 6 weeks, the concentration of TG in the blood plasma was significantly reduced. An additive effect is observed in combination with fenofibrate in relation to the content of triglycerides and with nicotinic acid in lipid lowering doses in relation to the content of HDL-C (see also the section ² ÑSpecial Instructions ² Ñ). According to the results of clinical studies, patients with severe hypercholesterolemia and a high risk of cardiovascular disease (CVD) should be prescribed a dose of 40 mg of Rosuvastatin-SZ. The results of a clinical study (The rationale for using statins for primary prevention: an interventional study evaluating rosuvastatin) showed that rosuvastatin significantly reduced the risk of developing cardiovascular complications.
Indications
– Primary Fredrickson hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet, when diet and other non-drug treatments (for example, physical exercises are insufficient) .
– Family homozygous hypercholesterolemia as a supplement to diet and other lipid lowering therapy (e.g., LDL apheresis), or in cases where such therapy is not effective enough.
– Hypertriglyceridemia (type IV according to Fredrickson) as a supplement to the diet.
– Primary dysbetalipoproteinemia (type III according to Frederickson) as a supplement to the diet.
– To slow the progression of atherosclerosis as a supplement to the diet in patients who are shown therapy to reduce the concentration of total cholesterol and LDL-C.
– Primary prophylaxis of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary artery disease, but with an increased risk of its development (over 50 years old for men and over 60 years old for women, increased concentration of C-reactive protein ( 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low concentration of HDL-C, smoking, family history of early onset of coronary heart disease).
Contraindications
For the drug Rosuvastatin-SZ in a daily dose of 5 mg, 10 mg and 20 mg:
– hypersensitivity to rosuvastatin or any of the components of the
drug – lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose)
– children under 18 years old
– liver disease in the active phase, including a persistent increase in serum activity transaminases and any increase in the activity of transaminases in the blood serum (more than 3 times compared with the upper limit of normal)
– severe renal failure (CC less than 30 ml / min.)
– myopathy
– simultaneous Riyem cyclosporine
– in women: pregnancy, period of breastfeeding, the lack of adequate methods of contraception
– an increase in the concentration of creatine phosphokinase (CPK) in the blood by more than 5 times compared with the upper limit of normal
– combined use with HIV protease inhibitors
– in patients predisposed to the development of myotoxic complications
For rosuvastatin-C3 drug daily dose of 40 mg:
– hypersensitivity to rosuvastatin or any of the components of the drug
– lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose) s rdlkp – children under 18 years of age
– concomitant use of cyclosporine
– in women: pregnancy, period of breastfeeding, the lack of adequate methods of contraception
– an increase in the concentration of creatine phosphokinase (CPK) in the blood by more than 5 times compared with the upper limit of normal
– combined use with HIV protease inhibitors
– moderate and severe renal failure (CC less than 60 ml / min. )
– liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared with the upper limit of normal) for patients with risk factors Vitality of myopathy / rhabdomyolysis, namely:
– hypothyroidism
– myotoxicity while taking other HMG-CoA reductase inhibitors or fibrates in the history of
– excessive alcohol consumption
– condition, which can lead to an increase in the plasma concentration of rosuvastatin
– concomitant use of
fibrates – myopathy
– personal or family history of muscle diseases
– for patients of the Mongoloid race
Caution
For rosuvastatin-10 mg 10 mg daily: The presence of a risk of developing myopathy / rhabdomyolysis – renal failure, hypothyroidism, a personal or family history of hereditary muscle diseases and a previous history of muscle toxicity when using other HMG-Co inhibitors A-reductase or fibrate excessive alcohol consumption age over 65 years of age conditions in which there is an increase in the plasma concentration of rosuvastatin race (Mongoloid race) concurrent administration with fibrates (see section Pharmacokinetics ) a history of liver disease sepsis arterial hypotension extensive surgery, trauma, severe metabolic, endocrine or electrolyte disturbances or uncontrolled seizures. Concomitant use with colchicine and with ezetimibe (see section “Interaction with other drugs”). For the daily dose of rosuvastatin-SZ 40 mg: Renal insufficiency of mild severity (CC more than 60 ml / min) age over 65 years of liver disease in the history of sepsis arterial hypotension extensive surgery, trauma, severe metabolic, endocrine or electrolyte disturbances or uncontrolled convulsive seizures. Concomitant use with colchicine and with ezetimibe (see section “Interaction with other drugs”). Patients with liver failure There is no data or experience with the use of the drug in patients with more than 9 Child-Pugh scores (see the sections Pharmacodynamics and Special Instructions ).
Special instructions
Use with caution in the presence of risk factors for rhabdomyolysis (including renal failure, hypothyroidism, a personal or family history of hereditary muscle diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates), with chronic in patients over the age of 65, with a history of liver disease, sepsis, arterial hypotension, during extensive surgical interventions, injuries, severe metabolic endocrine or electrolyte disorders, with uncontrolled epilepsy, in people of Asian descent (Chinese, Japanese).
Therapy should be discontinued if the level of CPK is significantly increased (more than 5 times compared with VGN) or if muscle symptoms are pronounced and cause daily discomfort (even if the level of CPK is 5 times lower compared to VGN).
When using rosuvastatin in a dose of 40 mg, it is recommended to monitor renal function indices.
In most cases, proteinuria decreases or disappears during therapy and does not indicate the onset or progression of an existing kidney disease.
An increase in the incidence of myositis and myopathy in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid, azole antifungal drugs, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Thus, the simultaneous administration of rosuvastatin and gemfibrozil is not recommended. The ratio of risk to possible benefit should be carefully weighed with the combined use of rosuvastatin and fibrates or niacin.
It is recommended that liver function tests be determined prior to initiation of therapy and 3 months after initiation of therapy. The use of rosuvastatin should be discontinued or the dose should be reduced if the level of transaminase activity in the blood serum is 3 times higher than VGN.
In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying diseases should be performed before treatment with rosuvastatin.
Influence on the ability to drive vehicles and operate machinery
When engaging in potentially hazardous activities, patients should be aware that dizziness may occur during therapy.
Composition
Active ingredient: rosuvastatin calcium in terms of rosuvastatin ² 10 mg.
Excipients:
core – lactose monohydrate (milk sugar) – 44.3 mg calcium hydrogen phosphate dihydrate – 10.0 mg povidone (polyvinylpyrrolidone medium molecular weight) – 6.0 mg croscarmellose sodium (primellose) – 4.0 mg sodium stearyl fumarate – 1.2 mg of silicon dioxide colloidal dioxide (Aerosil) – 0.5 mg microcrystalline cellulose – 44.0 mg
shell – Opadray II (polyvinyl alcohol, partially hydrolyzed – 1.76 mg macrogol (polyethylene glycol) 3350 – 0.494 mg talc – 0 , 8 mg of titanium dioxide E 171 – 0.7668 mg soy lecithin E 322 – 0.14 mg aluminum varnish per dye-based indigo carmine – 0.0024 mg aluminum varnish dye-based azorubine – 0, 0204 mg aluminum dye based crimson dye [Ponceau 4R] – 0.0164 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 food intake. Before starting therapy with Rosuvastatin, the patient should begin 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. The recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 mg or 10 mg of the drug Rosuvastatin once a 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 larger after 4 weeks. In connection with the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug, increasing the dose to 40 mg, after an additional dose is higher than the recommended initial dose for 4 weeks of therapy, can be carried out only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) the desired result of therapy was not achieved when taking a dose of 20 mg, and which will be under the supervision of a specialist. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. A 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).
Homozygous hereditary hypercholesterolemia
Recommended starting dose is 20 mg once daily.
Elderly patients
Patients over the age of 65 are advised to start using the drug with a dose of 5 mg once a day.
Patients with renal failure
Dose adjustment is not required in patients with mild or moderate renal failure.
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 in 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 (see section “Contraindications”).
Special Populations.
Ethnic groups When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin among Japanese and Chinese was noted. This fact should be taken into account when prescribing Rosuvastatin to these patient groups. When prescribing doses of 10 mg 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.
Patients predisposed to myopathy
Administration of the drug at a dose of 40 mg is contraindicated in patients with factors which may indicate a predisposition to the development of myopathy. When prescribing doses of 10 mg and 20 mg, the recommended initial dose for this group of patients is 5 mg.
Use with concomitant therapy
With the simultaneous use of the drug with gemfibrozil, fibrates, nicotinic acid in a dose of more than 1 g / day, an initial dose of 5 mg is recommended for patients. The dose of Rosuvastatin should not exceed 10 mg once a day.
Side effects
Side effects observed when taking Rosuvastatin are usually mild and go away on their own. As with other HMG-CoA reductase inhibitors, the incidence of side effects is mainly dose-dependent. The frequency of adverse effects is presented as follows: often (> 1/100, <1/10) infrequently (> 1/1000, <1/100) rarely (> 1/10000, <1/1000) very rarely (<1 / 10000), the frequency is unknown (according to available data, it is not possible to establish the frequency of occurrence), including individual messages. immune system Rarely: hypersensitivity reactions, including angioedema. Endocrine system Often: type 2 diabetes mellitus From the central nervous system Often: headache, dizziness From the digestive tract Often: constipation, nausea, abdominal pain Rarely: pancreatitis From the skin integument Infrequently, rash urticaria From the musculoskeletal system Often: myalgia Rarely: myopathy (including myositis), rhabdomyolysis Other Often: asthenic syndrome From the urinary system Protein may be detected in patients receiving rosuvastatin. Changes in the amount of protein in the urine (from the absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10 to 20 mg of the drug, and in approximately 3% of patients receiving 40 mg of the drug. 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. From the musculoskeletal system When using the drug Rosuvastatin in all doses, and especially when taking doses of the drug in excess of 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy (including myositis), in rare cases – rhabdomyolysis with acute renal failure or without it. A dose-dependent increase in the activity of creatine phosphokinase (CPK) is observed in a small number of patients taking rosuvastatin. In most cases, it was mild, asymptomatic and temporary. In the case of increased activity of CPK (more than 5 times compared with the upper limit of normal), therapy should be suspended. On the part of the liver When using rosuvastatin, a dose-dependent increase in the activity of ² Ñliver ² Ñ transaminases is observed in a small number of patients. In most cases, it is insignificant, asymptomatic and temporary. Laboratory indicators When using Rosuvastatin, the following changes in laboratory parameters were also observed: an increase in the concentration of glucose, bilirubin, the activity of gamma-glutamyl transpeptidase, alkaline phosphatase, and dysfunction of the thyroid gland. Post-marketing use of The following side effects have been reported in the post-marketing use of rosuvastatin: From the digestive tract Very rare: jaundice, hepatitis Rarely: increased activity of ² Ñliver ² Ñ transaminases. Frequency unknown: diarrhea, fatal and non-fatal liver failure From the musculoskeletal system Very rare: arthralgia. Frequency unknown: Immuno-mediated necrotizing myopathy From the central nervous system Very rare: polyneuropathy, forgetfulness, amnesia, memory loss, confusion From the respiratory system Frequency unknown: cough, shortness of breath From the urinary system Very rarely: From the skin and subcutaneous fat Frequency unknown: Stevens-Johnson syndrome From the reproductive system and mammary gland Frequency unknown: gynecoma ment Other frequency is unknown: peripheral edema thrombocytopenia interstitial lung disease. The following side effects have been reported with some statins: depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction. Overdose of With the simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change. There is no specific treatment for an overdose of rosuvastatin. In case of an overdose, symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems are recommended. It is necessary to control liver function and CPK level. Hemodialysis is unlikely to be effective. Storage conditions Store in a dry, dark place at a temperature not exceeding 30 ° C. active substance Rosuvastatin Terms and conditions by recipe lekarstvennaja form tablets