Description
Pharmacological action of
Mechanism of action of
Rosuvastatin is a selective, competitive inhibitor of GM G-CoAg reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. 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 hepatic 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 reduces the increased concentration of LDL cholesterol (LDL-C), total cholesterol, triglycerides (GH), increases the concentration of high-density cholesterol-lipoproteins (HDL-C), and also reduces the concentration of apolipoprotein B (ApoV), non-HDL cholesterol, cholesterol-VLDL, TG-VLDL and increases the level of apolipoprotein AI (ApoA-1), reduces the ratio of LDL-C / Cholesterol-HDL, total cholesterol / cholesterol-HDL and cholesterol-free HDL / cholesterol-HDL and the ratio of ApoV / ApoA-1.
The therapeutic effect appears within one week after the start of therapy with rostatin, after 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by the 4th week and is maintained with regular use of the drug.
Clinical efficacy of
Rosuvastatin is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender or age, incl. in patients with diabetes mellitus and familial hypercholesterolemia.
In 80% of patients with hypercholesterolemia Na and lib type according to the Fredrickson classification (average initial concentration of LDL-C is about 4.8 mmol / L) with a dose of 10 mg, the concentration of LDL-C reaches less than 3 mmol / L.
In patients with heterozygous familial hypercholesterolemia receiving rosuvastatin 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 patients with homozygous familial hypercholesterolemia taking rosuvastatin at a dose of 20 mg and 40 mg, the average decrease in LDL-C concentration is 22%. An additive effect is observed in combination with fenofibrate in relation to the concentration of triglycerides and with nicotinic acid in lipid lowering doses (more than 1 g / day) in relation to the concentration of HDL-C.
Indications
Primary hypercholesterolemia according to the classification of Fredrickson (type Na, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type lib) as a supplement to diet, when diet and other non-drug methods of treatment (for example, physical exercises, weight loss) .
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 the classification of Fredrickson) as a supplement to the diet.
To slow the progression of atherosclerosis as a supplement to patients diet, which shows therapy to reduce the concentration of total cholesterol and cholesterol-LDL.
Primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), 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, a family history of early onset of CHD).
Contraindications
hypersensitivity to rosuvastatin or any of the components of the drug
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)
severe disorders kidney function (CC less than 30 ml / min. )
myopathy
simultaneous administration of cyclosporine
children and adolescents under 18 years of age
in women: pregnancy, the period of breastfeeding, lack of adequate methods of contraception
in patients predisposed to the development of myotoxic complications, lactose intolerance, lactose-mediated lactose or lactose deficiency (glucose-lactose deficiency or lactose-free absorption) lactose).
Precautions
Presence of a risk of myopathy / rhabdomyolysis – renal failure, hypothyroidism, personal or family history of inherited muscle diseases and a previous history of muscle toxicity with other HMG-CoA reductase inhibitors or
fibrates excessive alcohol consumption srdl old srdl , in which an increase in the plasma concentration of rosuvastatin
was noted racial affiliation (Mongoloid race)
simultaneous administration of liver disease with
fibrates in the history of
sepsis
arterial hypotension
extensive surgical interventions, injuries, severe necrosis, or neuro-abnormal necrolitosis, endocrine, neuroprolitic, or neuroprolitic necrosis, endometriosis, or neurosurgical
Special instructions for
From the urinary system
In patients who received high doses of rosuvastatin (mainly 40 mg), tubular proteinuria was observed, which in most cases was transient. Such proteinuria did not indicate acute kidney disease or progression of kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor renal function indicators during treatment.
From the musculoskeletal system
When using rosuvastatin in all dosages and, especially when taking doses of the drug in excess of 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy, in rare cases, rhabdomyolysis.
Determination of creatine phosphokinase activity
Determination of CPK activity should not be carried out after intense physical activity or if there are other possible reasons for the increase in CPK activity, which may lead to an incorrect interpretation of the results. If the initial activity of CPK is significantly increased (5 times higher than the upper limit of the norm), a repeated measurement should be carried out after 5-7 days.
Do not start therapy, if a repeated test confirms the initial activity of CPK (more than 5 times higher than the upper limit of the norm).
Before starting
therapy When prescribing the drug Ro-statin, as well as when prescribing other inhibitors of HMG-CoA reductase, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis, it is necessary to consider the risk and potential benefits of therapy and conduct clinical observation.
During
therapy, the patient should be informed of the need to immediately inform the doctor of cases 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 CPK activity is significantly increased (more than 5 times compared with the upper limit of the norm) or if the symptoms on the part of the muscles are pronounced and cause daily discomfort (even if the CPK activity is 5 times lower compared to the upper limit of the norm).
If symptoms disappear and KFK activity returns to normal, consideration should be given to re-prescribing the drug Ro-statin or other HMG-CoA reductase inhibitors in lower doses with careful monitoring of the patient. Routine monitoring of CPK activity 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 an increase in serum CPK activity during treatment or when stopping statins, including rosuvastatin.
Additional studies of the muscular system and nervous system, serological tests, and immunosuppressive therapy may be required.
There were no signs of increased effects on skeletal muscle when taking Ro-statin and concomitant therapy. However, an increase in the incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid lowering doses (more than 1 g / day), azole antifungal agents, inhibitors HIV proteases and macrolide antibiotics.
Gemfibrozil increases the risk of myopathy when used together with certain HMG-CoA reductase inhibitors. Thus, simultaneous use of the drug Ro-statin and gemfibrozil is not recommended. The ratio of risk and possible benefit should be carefully weighed when the combined use of the drug Ro-statin and fibrates or lipid-lowering doses of nicotinic acid (more than 1 g / day).
Administration of the drug Ro-statin in a dose of 40 mg is contraindicated in conjunction with fibrates. 2-4 weeks after the start of treatment and / or with an increase in the dose of Ro-statin, monitoring of lipid metabolism is necessary (dose adjustment is necessary if necessary).
Effect on liver function
It is recommended that liver function tests be determined before starting therapy and 3 months after starting therapy. Administration of the drug Ro-statin should be discontinued or the dose of the drug should be reduced if the activity of liver transaminases in the blood serum is 3 times higher than the upper limit of normal.
In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy of the main diseases should be carried out before treatment with the drug Ro-statin.
Special Populations.
Ethnic groups
Pharmacokinetic studies among Chinese and Japanese patients showed an increase in systemic concentrations of rosuvastatin compared with those obtained among European patients.
HIV protease inhibitors
The combined use of the drug with HIV protease inhibitors is not recommended.
Lactose
The drug should not be used in patients with lactase deficiency, galactose intolerance and glucose-galactose malabsorption.
Interstitial pulmonary disease
With some statins, 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 you suspect an interstitial lung disease, statin therapy 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 developing type 2 diabetes. HMG-CoA reductase inhibitors, including Ro-statin may increase blood glucose concentration.
Effect on the ability to drive vehicles and other mechanisms
No studies have been conducted to study the effect of rosuvastatin on the ability to drive a vehicle and use mechanisms. Caution should be exercised when driving a car or working related to increased concentration of attention and psychomotor reaction (dizziness may occur during therapy).
Composition
Active ingredient:
rosuvastatin calcium – 5.210 megapixels in terms of rosuvastatin -5,000 mg.
Excipients:
lactose monohydrate (milk sugar) -144.824 mg
microcrystalline cellulose – 25.344 mg
croscarmellose sodium – 9.311 mg
povidone-K25 -5, 431 mg
silicon dioxide colloidal -1.940 mg
magnesium stearate – 1.940 mg
Capsule body composition: iron oxide black oxide – 0.05%, titanium dioxide – 2%, gelatin up to 100%.
Composition of capsule cap: iron dye black oxide – 0.05%, titanium dioxide – 2%, gelatin up to 100%.
Dosage and administration
Inside, do not chew or open the capsule, 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 Ro-statin, 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 the target concentration of lipids.
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 or 10 mg of the drug Ro-statin once a day.
When choosing an initial dose, you should be guided by an individual concentration of cholesterol 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.
Due to 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 only be performed in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially 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.
Especially careful monitoring of patients receiving the drug in 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 Ro-statin, monitoring of lipid metabolism is necessary (dose adjustment is necessary if necessary).
Elderly patients
The initial recommended dose for patients over the age of 70 years is 5 mg, the rest does not require dose adjustment depending on age.
Patients with renal failure
Dose adjustment is not required in patients with mild or moderate renal failure. The use of all dosages of the rostatin drug is contraindicated in patients with severe renal failure (CC less than 30 ml / min.). The use of the drug in a dosage of 40 mg is contraindicated in patients with moderate impaired renal function (CC less than 60 ml / min.).
For patients with moderate impaired renal function (CC less than 60 ml / min.), an initial dose of 5 mg is recommended.
Patients with liver failure
The drug Ro-statin 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 was noted among Japanese and Chinese. This fact should be taken into account when prescribing Ro-statin to these patient groups.
When prescribing doses of 10 and 20 mg, the recommended starting dose for patients of the Mongoloid race is 5 mg.
Contraindication of the drug at a dose of 40 mg to 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 that may indicate a predisposition to the development of myopathy. When prescribing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg.
Genetic polymorphism
In carriers of genotypes SLC01B1 (OATP1B1) c.521CChABCG2 (BCRP) s.421AA, an increase in exposure (AUC) to rosuvastatin was noted compared to carriers of genotypes SLC01B1 C.521TT and ABCG2 C.421CC. For patients carriers of genotypes C.521CC or C.421AA, the recommended maximum dose of the drug Ro-statin is 20 mg once a day.
Concomitant therapy
Rosuvastatin binds to various transport proteins (in particular, OATP1B1 and BCRP). With the simultaneous use of the drug Ro-statin with 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 the blood plasma due to interaction with transport proteins, the risk of myopathy (including rhabdomyolysis) may increase.
In such cases, you should evaluate the possibility of prescribing alternative therapy or temporarily stop taking Ro-statin. If the use of the above drugs is necessary, the ratio of the benefit and risk of concomitant therapy with Ro-statin should be assessed and the possibility of reducing its dose considered.
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 dose-dependent.
The frequency of adverse effects is presented as follows, according to the WHO classification:
Often (> 1/100, <1/10) Infrequently (> 1/1000, <1/100) Rarely (> 1/10 000, <1/1000 ) Very rarely (<1/10000), including individual messages The frequency is not set (cannot be calculated according to the available data). 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: itching, rash, urticaria br> From the musculoskeletal system
Often: myalgia
Rarely: myopathy (including myositis srdld, slave Often: asthenic
syndrome From the urinary system
Progeinuria 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, progeinuria 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 rosuvastatin in all dosages 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 creatine phosphokinase (CK) activity was 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
Increased concentrations of glucose, bilirubin, activity of gamma-glutamyl transpeptidase, alkaline phosphatase, thyroid dysfunction.
Post-marketing use of
The following side effects have been reported in the post-marketing use of rosuvastatin:
From the hematopoietic system:
Rarely: thrombocytopenia.
From the digestive tract
Very rare: jaundice, hepatitis
Rarely: increased activity of hepatic transaminases
Frequency not found: diarrhea
From the musculoskeletal system
Very rare: arthralgia
Frequency not found: immuno-mediated necrotizing myopathy.
From the central nervous system
Very rare: polyneuropathy, memory loss
From the respiratory system
Frequency not found: cough, shortness of breath.
Urinary system
Very rare: hematuria.
From the skin and subcutaneous fat
Frequency not found: Stevens-Johnson syndrome
From the reproductive system
Frequency not found: gynecomastia.
Other
Frequency not found: peripheral edema.
The following side effects have been reported with some statins: depression, sleep disturbances, including insomnia and ² Ñnightmare ² Ñ dreams, sexual dysfunction. Isolated cases of interstitial lung disease have been reported, especially with prolonged use of drugs.
Overdose
Symptoms: with the simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.
Treatment: There is no specific treatment for an overdose of rosuvastatin. In case of an overdose, symptomatic treatment and measures are recommended, aimed at maintaining the functions of vital organs and systems. It is necessary to control liver function and CPK level. Hemodialysis is unlikely to be effective.
Storage conditions
In a dark place at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
Expiration
3 years.
Do not use after expiration date.
Terms and conditions otpuska IZ
pharmacy prescription
dosage form
capsules
