Acorta - instructions for use, dose, side effects, contraindications

Active substance: rosuvastatin calcium - 10.4 mg or 20.8 mg (in terms of anhydrous substance, equivalent to the content of rosuvastatin - 10.0 mg or 20.0 mg).

Excipients:

core:

for the dosage of 10 mg - lactose monohydrate (milk sugar) - 89.50 mg, microcrystalline cellulose - 29.82 mg, calcium hydrophosphate (E 341) - 10.90 mg, crospovidone - 7.50 mg, magnesium stearate - 1.88 mg;

for dosage of 20 mg - lactose monohydrate (sugar milk) - 179.00 mg, microcrystalline cellulose - 59.64 mg, calcium hydrophosphate (E 341) - 21.80 mg, crospovidone - 15.00 mg, magnesium stearate - 3.76 mg;

shell:

for the dosage of 10 mg - OUADRAI II 30K240001 Pink (ORADY II 30K240001 Rink) [lactose monohydrate (sugar milk) - 2.40 mg, hypromellose (hydroxypropylmethylcellulose) 1.68 mg, titanium dioxide -1.413 mg, triacetin (glyceryl triacetate) -0.48 mg, iron-oxide red oxide -0.027 mg] 6.00 mg;

for dosage of 20 mg - OUADRAI II 30K240001 Pink (ORADY II 30K240001 Rink) [lactose monohydrate (milk sugar) - 4.80 mg, hypromellose (hydroxypropylmethylcellulose) - 3.36 mg, titanium dioxide -2.826 mg, triacetin (glyceryl triacetate) -0.96 mg, iron-oxide red oxide -0.054 mg] 12.00 mg.

Pharmacotherapeutic group:lipid-lowering agent - HMG-CoA reductase inhibitor

ATX: & nbsp

C.10.A.A Inhibitors of HMG-CoA reductase

C.10.A.A.07 Rosuvastatin

Pharmacodynamics:Rosuvastatin is a selective competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl-CoA to mevalonate, which is a precursor of cholesterol. The main target of the action of rosuvastatin is the liver, where the synthesis of cholesterol (cholesterol) and catabolism of low-density lipoprotein (LDL) is carried out. Rosuvastatin increases the number of LDL receptors on the surface of hepatocytes, increasing the uptake and catabolism of LDL. It also inhibits the synthesis of cholesterol-lowering lipoprotein (LDL) cholesterol in liver cells, thereby reducing the total amount of LDL and VLDL.

Rosuvastatin reduces the concentration of cholesterol-LDL, total cholesterol and triglycerides (TG), increases the concentration of high-density lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (ApoB),cholesterol-non-HDL cholesterol (the concentration of total cholesterol, minus the content of cholesterol-HDL-C), cholesterol-VLDL, TG-VLDL and increases the concentration of apolipoprotein A-1 (ApoA-1). Rosuvastatin reduces the ratio of LDL-C-HDL cholesterol, total cholesterol / cholesterol-HDL cholesterol, cholesterol-HDL cholesterol and LDL cholesterol and ApoA / ApoA-1.

The hypolipidemic effect is directly proportional to the magnitude of the prescribed dose. The therapeutic effect develops within 1 week after the start of therapy, after 2 weeks reaches 90% of the maximum possible effect, the maximum therapeutic effect is usually achieved after 4 weeks and is maintained with further administration of the drug. Effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender or age), incl. in patients with diabetes mellitus and hereditary form of familial hypercholesterolemia. The additive effect is noted in combination with fenofibrate (in terms of decreasing TG concentration) and nicotinic acid in lipid-lowering doses (more than 1 g / day) (for increasing cholesterol-HDL-C).

Pharmacokinetics:

Absorption: absolute bioavailability - 20%. The food reduces the suction speed.Time to reach the maximum concentration (TCmah) 3-5 hours after ingestion. Penetrates through the placental barrier.

Distribution: rosuvastatin is absorbed mainly by the liver, which is the site of cholesterol synthesis and the metabolism of LDL-C. The distribution volume is about 134 liters. The connection with blood plasma proteins (mainly with albumin) is 90%.

Metabolism: in the liver, 10% of the dose is metabolized. Rosuvastatin is a non-core substrate for metabolism by enzymes of the cytochrome P450 system. СУР2С9 is the main isoenzyme involved in the metabolism of rosuvastatin, while isoenzymes СУР2С19, СУР3А4, СУР2D6 are involved in its metabolism to a lesser extent. More than 90% of the pharmacological activity of inhibiting the circulating HMG-CoA reductase is provided by rosuvastatin, the rest - by its metabolites. The main revealed metabolites of rosuvastatin are N-dysmethyl and lactone metabolites. N-dimethyl is about 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive.

Excretion: is mainly excreted unchanged (90%) through the intestine (including absorbed and unabsorbed rosuvastatin); the rest is with the kidneys.The half-life (T1 / 2) is approximately 19 hours. The half-life does not change with increasing dose of the drug. The average geometric plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase inhibitors, the membrane hepatic transport of cholesterol is involved in the "hepatic" capture of rosuvastatin (transport protein C organic anions), which plays an important role in the hepatic elimination of rosuvastatin. The systemic exposure of rosuvastatin increases in proportion to the dose. Changes in pharmacokinetic parameters with daily administration of the drug are not noted.

Sex and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.

Ethnic groups

Pharmacokinetic studies showed approximately a twofold increase in the median AUC (the area under the concentration-time curve) and Cmax (maximum concentration in blood plasma) of rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared to Europeans mi; Indian patients showed an increase in the median AUC and FROMmax in 1,3 times.Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics among Europeans and representatives of the Negroid race.

Renal insufficiency

In patients with mild and moderate renal failure, the plasma concentration of rosuvastatin or N-dimethyl does not change significantly. In patients with severe renal insufficiency (creatinine clearance <30 ml / min), the concentration of rosuvastatin in the blood plasma is 3 times higher, and N-dimethyl is 9 times higher than in healthy volunteers. The concentration of rosuvastatin in plasma in patients on hemodialysis is approximately 50% higher than in healthy volunteers.

Liver failure

In patients with different stages of hepatic insufficiency with a score of 7 or lower on the Child-Pugh scale, there was no increase in T1 / 2 rosuvastatin; in 2 patients with a score of 8 and 9 on the Child-Pugh scale, a T1 / 2 elongation was observed that was 2 times greater than that for patients with lower Child-Pugh scores. Experience with the drug in patients with more severe impairment of liver function (above 9 on the Child-Pugh scale) is not available.

Genetic polymorphism

Inhibitors of HMG-CoA reductase, including, rosuvastatin, bind to transport proteins OATP1B1 (a polypeptide transporting organic anions involved in the capture of the inhibitor of HMG-CoA reductase by hepatocytes) and BCRP (efflux conveyor). In carriers of genotypes SLCO1B1 (OATP1B1) C.521SS and / or ABCG2 (ВСRР) С.421АА there is a risk of increasing the exposure of rosuvastatin (AUC) in comparison with the carriers of genotypes SLCO1В1 С.521ТТ and АВСG2 P.421S.

Indications:

Primary hypercholesterolemia according to Fredriksen (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet, when diet and other non-pharmacological methods of treatment (for example, physical exercises, weight loss) are insufficient.

Family homozygous hypercholesterolemia - as a supplement to the diet and other lipid-lowering therapy (eg, LDL-apheresis) or in cases when such therapy is not effective enough. Hypertriglyceridemia (type IV according to Fredriksen) 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 prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adults 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 C-reactive protein (> 2 mg / L) in the presence of at least one of the risk factors, such as hypertension, low concentration of HDL-C, a family history of early onset of coronary artery disease).

Contraindications:For the drug in a daily dose of 10 and 20 mg: increased sensitivity to rosuvastatin or any of the components of the drug, liver disease in the active phase (including a persistent increase in the activity of "liver" transaminases, as well as any increase in the activity of "liver" transaminases in the serum more than 3 times compared with the upper (KK less than 30 ml / min), lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose), myopathy, simultaneous administration of cyclosporine, predisposition to p zvitiyu miotoksicheskih complications, pregnancy,lactation period; use in women of reproductive age not using reliable methods of contraception; age to 18 years (efficacy safety not established).

In a daily dose of 40 mg: in addition to the above contraindications, the drug is contraindicated in hypothyroidism, personal or family history of muscle disease, myotoxicity when taking other inhibitors of HMG-CoA reductase or fibrates in history, excessive alcohol consumption, conditions that may lead to an increase in the concentration of rosuvastatin in blood plasma, patients of the Mongoloid race, simultaneous reception of fibrates, renal failure of moderate severity (CC less than 60 ml / min).

Carefully:For the preparation in a daily dose of 10 and 20 mg: the presence of a risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates, excessive alcohol consumption, the conditions under which there is an increase in the plasma concentration of rosuvastatin, age over 65,a history of liver disease, sepsis, arterial hypotension, extensive surgery, trauma, severe metabolic, endocrine or water-electrolyte disorders, uncontrolled epilepsy, race (Mongoloid race), simultaneous reception of fibrates.

For the drug in a daily dose of 40 mg: renal failure of mild severity (CC greater than 60 ml / min); age over 65; liver disease in history; sepsis; arterial hypotension; extensive surgical interventions, trauma, severe metabolic, endocrine or water-electrolyte disorders or uncontrolled convulsive seizures.

Pregnancy and lactation:The drug Acorta® is contraindicated for use during pregnancy and during breastfeeding. Women of reproductive age should apply reliable and adequate methods of contraception. Because cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of using the drug in pregnant women. When establishing pregnancy in the course of therapy, taking the drug should be stopped immediately.Data on the allocation of rosuvastatin to breast milk are not available, so during breastfeeding, the drug should be discontinued.

Dosing and Administration:Before starting therapy with the drug, the patient should begin to follow the standard lipid-lowering diet and continue to observe it during treatment. The dose of the drug should be selected individually, depending on the purpose of therapy and the therapeutic response, taking into account current generally accepted recommendations for target lipid concentrations. The drug Akorta ® is taken inside, at any time of the day, regardless of the meal, without chewing and grinding the tablet, swallowing whole, washing down with water. The recommended initial dose of rosuvastatin (if not prescribed otherwise) is 10 mg once a day for patients who have not previously taken HMG-CoA reductase inhibitors, and for patients transferred to receive this drug after treatment with other HMG-CoA reductase inhibitors . When choosing the initial dose should be guided by the individual value of cholesterol concentration 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 after 4 weeks to 20 mg. 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, can be carried out only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) , who did not achieve the desired result of therapy when taking a dose of 20 mg, and which will be under medical supervision. It is recommended especially careful monitoring of patients receiving the drug in a dose of 40 mg. Do not administer a dose of 40 mg to patients who have not previously consulted a doctor. After 2-4 weeks of therapy and / or with an increase in the dose of the drug, control of lipid metabolism parameters is necessary (if necessary, dose correction is required). In patients taking the drug at a dose of 40 mg, it is recommended to monitor the indicators of kidney function. Older patients do not need a dose adjustment.

When studying the pharmacokinetic parameters in patients,belonging to different ethnic groups, there was an increase in the systemic concentration of rosuvastatin among Japanese and Chinese. This fact should be taken into account in the appointment of rosuvastatin to these patient groups. Contraindicated the appointment of the drug in a dose of 40 mg to patients of the Mongoloid race.

Patients with renal insufficiency

In patients with mild or moderate renal insufficiency, dose adjustment is not required. Contraindicated use of all dosages of Acorta ® in patients with severe renal failure (creatinine clearance less than 30 ml / min). Contraindicated use of the drug at a dosage of 40 mg in patients with moderate impaired renal function (creatinine clearance less than 60 ml / min).

Patients with hepatic insufficiency

The experience of using the drug in patients with a score above 9 on the Child-Pugh scale is not available. The drug Acorta ® is contraindicated in patients with liver diseases in the active phase (including with a persistent increase in the activity of "liver" transaminases, as well as any increase in the activity of "liver" transaminases in the serum more than 3 times compared with the upper limit of the norm).

Genetic polymorphism

In carriers of genotypes SLFROMO1В1 (ОАТР1В1) С.521СС and АВСG2 (ВСRP) C.421AA, an increase in exposure (AUC) to rosuvastatin in comparison with carriers of genotypes SLCO1В1 С.521ТТ and АВСG2 p.421S. For patients carrying genotypes с.521СС and С.421АА the recommended maximum dose of the drug is 20 mg once a day.

Patients who are predisposed to myopathy

Contraindicated the appointment of the drug in a dose of 40 mg to patients with factors that may indicate a predisposition to the development of myopathy.

Concomitant therapy

Rosuvastatin binds to various transport proteins (in particular, to OATP1B1 and VSRR). When combined with drugs (such as cyclosporine, some HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir, and / or tipranavir), increasing the concentration of rosuvastatin in blood plasma by interacting with transport proteins may increase the risk of myopathy (including rhabdomyolysis). In such cases, the possibility of prescribing alternative therapy or temporarily discontinuing the use of Acorta® should be evaluated.If the use of the above drugs is necessary, the ratio of expected benefit to the possible risk of concomitant therapy with AcorTaand consider the possibility of reducing its dose.

Side effects:

As with other HMG-CoA reductase inhibitors, the incidence of side effects is dose-dependent.

Frequency of occurrence of side effects: often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10 000, <1/1000); very rarely (<1/10 000); unrefined frequency (can not be calculated from available data).

From the central and peripheral nervous system: often - headache, dizziness, asthenic syndrome; infrequently - anxiety, neuralgia, paresthesia, very rarely - polyneuropathy, amnesia.

From the digestive system: often - constipation, nausea, abdominal pain; rarely - a reversible transient dose-dependent increase in the activity of "liver" transaminases, pancreatitis; very rarely - dyspepsia (including diarrhea, flatulence, vomiting), gastroenteritis, jaundice, hepatitis.

From the respiratory system: often pharyngitis; infrequently - rhinitis, sinusitis, bronchial asthma, bronchitis, pneumonia; unconfirmed frequency - cough, dyspnea.

From the cardiovascular system: infrequently - angina, increased blood pressure, palpitations, symptoms of vasodilation (including skin hyperemia).

From the musculoskeletal system: often - myalgia; infrequently - arthritis, muscle hypertonus, back pain, pathological fracture of limb bones (without damage); rarely - myopathy, rhabdomyolysis (simultaneously with impaired renal function, against the background of taking the drug at a dose of 40 mg); very rarely - arthralgia; Unspecified frequency - immuno-mediated necrotic myopathy, tendopathies, sometimes complicated by ruptures.

From the urinary system: proteinuria (in less than 1% of cases - for doses of 10 mg and 20 mg, 3% for doses of 40 mg). In most cases, proteinuria decreases or disappears during therapy and does not indicate the onset or progression of an existing kidney disease; very rarely - hematuria.

Allergic reactions: infrequently - skin rash, itching, hives; rarely - angioedema; Unspecified frequency - Stevens-Johnson syndrome.

From the laboratory indicators: an increase in the concentration of glucose in the blood plasma, bilirubin, an increase in the activity of gamma-glutamyltranspeptidase, alkaline phosphatase.A dose-related increase in creatine phosphokinase (CK) activity was observed in a small number of patients taking rosuvastatin. In most cases, it was insignificant, asymptomatic and temporary. When the activity of CK is increased by more than 5 times compared with the upper limit of the norm, therapy should be temporarily suspended.

Other: often - type 2 diabetes mellitus; infrequently - anemia, chest pain, ecchymosis, flu-like syndrome, periodontal abscess; rarely thrombocytopenia; Unspecified frequency - peripheral edema, gynecomastia. Some statins reported the following side effects: depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction. Single cases of interstitial lung disease have been reported, especially with prolonged use of drugs (see Special instructions).

Overdose:Symptoms: increased side effects. With the simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change. Treatment: there is no specific antidote.It is recommended to carry out symptomatic treatment and activities aimed at maintaining the functions of vital organs and systems. It is necessary to monitor the liver function and the activity of creatine phosphokinase. Hemodialysis is ineffective.

Interaction:

Effect of the use of other drugs on rosuvastatin

Transport protein inhibitors: rosuvastatin binds to some transport proteins, in particular, to OATP1B1 and BCRR. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of myopathy.

Rosuvastatin does not affect the plasma concentration of cyclosporine. Cyclosporin enhances the effect of rosuvastatin (slows down its excretion, increases AUFROM 7 times, CmOh - 11 times).

Gemfibrozil enhances the effect of rosuvastatin (increases its Cmax and AUC in 2 times). Gemfibrozil, fenofibrate and other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g / day) increase the risk of myopathy with concomitant use with HMG-CoA reductase inhibitors, possibly due to the fact that they themselves can cause myopathy when used in monotherapy.

Taking the drug in a dose of 40 mg is contraindicated in a joint appointment with fibrates. When administered with gemfibrozil, the dose of rosuvastatin should not exceed 10 mg / day.

Despite the fact that the exact mechanism of interaction is unknown, joint intake of HIV protease inhibitors can lead to a significant increase in exposure to rosuvastatin. A pharmacokinetic study on the simultaneous use of 20 mg rosuvastatin with a combined preparation containing two HIV protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers resulted in approximately a twofold and fivefold increase in AUC (a-24) and Cmrosuvastatin, respectively. Therefore, simultaneous administration of rosuvastatin and HIV protease inhibitors is not recommended.

Antatsidy containing ions of aluminum and magnesium, lead to a decrease in the plasma concentration of rosuvastatin by about 50% (antacids should be used 2 hours after taking rosuvastatin, the clinical significance of this interaction has not been studied). Erythromycin strengthens the motility of the gastrointestinal tract, which leads to a decrease in the effect of rosuvastatin (reduces its AUC by 20% and C_m_Oh on 30%).

Research results in vivo and in vitro showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Besides, rosuvastatin is a non-core substrate for these enzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (inhibitor of isoenzymes СUR2С9 and СУР3А4) and ketoconazole (inhibitor of isoenzymes СUR2А6 and СУРЗА4). The combined use of rosuvastatin and itraconazole (inhibitor CUR3A4) increases AUWith rosuvastatin by 28% (clinically insignificant). Thus, the interaction associated with metabolism through the cytochrome P450 system is not expected.

The simultaneous use of rosuvastatin in a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in AUWith rosuvastatin in patients with hypercholesterolemia. However, the pharmacodynamic interaction of rosuvastatin and ezetimibe, which can cause undesirable effects, can not be ruled out.

Interaction with drugs, which requires correction of the dose of rosuvastatin (see Table 1)

The dose of rosuvastatin should be adjusted when necessary for joint use with drugs that increase its exposure.Also, the maximum daily dose should be adjusted, so that the expected exposure of ro zuvastatin did not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs interacting with rosuvastatin.

Table 1. Effect of the joint use of drugs on the exposure of rosuvastatin (AUC, in descending order of magnitude) according to published clinical studies

Dosing regimen of concomitant drugs	The dosage regimen of rosuvastatin	Change in the exposure of rosuvastatin (AUFROM)
Cyclosporine 75 mg twice daily to 200 mg twice daily, 6 months	10 mg once a day, 10 days	an increase of 7.1 times
Atazanavir 300 mg / ritonavir 100 mg once a day, 8 days	10 mg, once	increase by 3.1 times
Lopinavir 400 mg / ritonavir 100 mg twice daily, 17 days	20 mg once a day, 7 days	an increase of 2.1 times
Clopidogrel heated 300 mg (loading dose), then 75 mg after 24 hours.	20 mg once	increase 2 times
Gemfibrozil 600 mg twice a day, 7 days	80 mg, once	an increase of 1.9 times
Eltrombopag 75 mg once a day, 10 days	10 mg, once	an increase of 1.6 times
Darunavir 600 mg / ritonavir 100 mg twice daily, 7 days	10 mg once a day, 7 days	an increase of 1.5 times
Tipranavir 500 mg / ritonavir 200 mg twice daily, 11 days	10 mg, once	an increase of 1.4 times
Dronedarone 400 mg twice daily	no data	an increase of 1.4 times
Itraconazole 200 mg once a day, 5 days	10 mg, once	an increase of 1.4 times
Ezetimibe 10 mg once a day, 14 days	10 mg once a day, 14 days	an increase of 1.2 times
Fosamprenavir 700 mg / ritonavir 100 mg twice daily, 8 days	10 mg, once	unchanged
Aleglitazar 0.3 mg, 7 days	40 mg, 7 days	unchanged
Silymarin 140 mg three times a day, 5 days	10 mg, once	unchanged
Fenofibrate 67 mg three times a day, 7 days	10 mg, 7 days	unchanged
Rifampicin 450 mg once daily, 7 days	20 mg, once	unchanged
Ketoconazole 200 mg twice daily, 7 days	80 mg, once	unchanged
Fluconazole 200 mg once daily, 11 days	80 mg, once	unchanged
Erythromycin 500 mg 4 times a day, 7 days	80 mg, once	decrease by 28%
Baikalin 50 mg three times a day, 14 days	20 mg, once	decrease by 47%

Effect of rosuvastatin on other drugs

The beginning of rosuvastatin therapy or an increase in the dose of the drug in patients receiving simultaneously vitamin K antagonists (for example, warfarin), can lead to an increase in prothrombin time (an increase in the international normalized relationship (INR)). Removing rosuvastatin or reducing its dose may result in a decrease in INR (in such cases, monitoring of INR is recommended).

Rosuvastatin increases the effect of oral contraceptives (increases AUFrom ethinyl estradiol and norgestrel by 26% and 34%, respectively, which should be considered when choosing a dose of oral kon traps). Pharmacokinetic data on simultaneous use of rosuvastatin and hormone replacement therapy are absent, therefore, it is impossible to exclude a similar effect when using this combination.

No clinically significant interaction between rosuvastatin and digoxin is expected.

Special instructions:Proteinuria, mainly of tubular origin, was noted in patients receiving high doses of rosuvastatin, in particular 40 mg, but in most cases it was periodic or transient. It is shown that such proteinuria does not mean the emergence of acute or progressive disease of the existing kidney disease.In patients taking the drug at a dose of 40 mg, it is recommended to monitor the performance of kidneys during treatment.

Determination of CKK activity should not be performed after intensive physical exertion or in the presence of other possible causes of increased activity of CK, which may lead to incorrect interpretation of the results. With an increase in the initial activity of CK 5 times higher than the upper limit of the norm, after 5-7 days, a second measurement should be made. Do not start therapy if the repeated test confirms the initial increased activity of CK more than 5 times compared with the upper limit of the norm.

Patients with risk factors for rhabdomyolysis should consider the relationship between risk and the potential benefits of therapy and carry out clinical follow-up throughout the course of treatment.

The patient should be informed of the need to report immediately to the doctor about cases of sudden onset of muscle pain, muscle weakness, or spasms, especially in combination with malaise and fever. These patients should be monitored for the level of activity of CK.Therapy should be discontinued if the activity of CK is increased more than 5 times in comparison with the upper limit of the norm, or if the muscle symptoms are pronounced and cause daily discomfort (even if the activity of CK is 5 times less than the upper limit of the norm). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-administering the drug or other HMG-CoA reductase inhibitors in smaller doses with careful monitoring of the patient. Routine monitoring of CKK in the absence of symptoms of rhabdomyolysis is inexpedient. Very rare cases of immuno-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of proximal muscles and increased activity of CKK in blood serum during treatment or with stopping of taking statins, including rosuvastatin, have been noted. It may be necessary to conduct additional studies of the muscular and nervous system, serological studies, as well as therapy with immunosuppressive drugs.

An increase in the incidence of myositis and myopathy in patients was reported,Other inhibitors of HMG-CoA reductase in combination with derivatives of fibroic acid (including gemfibrozil), cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungals, HIV protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Thus, simultaneous use of rosuvastatin and gemfibrozil is not recommended. A balance of risk and possible benefit should be carefully weighed in the combined use of rosuvastatin and fibrates or nicotinic acid in lipid-lowering doses. Contraindicated taking Acorta ® in a dose of 40 mg together with fibrates. Acorta® should not be given to patients with acute, severe illnesses suggesting myopathy or the possible development of secondary renal failure (sepsis, arterial hypertension, surgery, trauma, metabolic syndrome, seizures, endocrine disorders, water-electrolyte disorders).The drug Acorta ®, like other inhibitors of HMG-CoA reductase, should be taken with extreme caution in patients who abuse alcohol or who have a history of liver disease. After 2-4 weeks after the start of therapy and / or when the dose of Acorta ® is increased, it is necessary to monitor the lipid metabolism (if necessary, dose adjustment is required). It is recommended to carry out the determination of the activity of "liver" transaminases before the start of therapy and 3 months after the initiation of therapy. If the activity of "hepatic" transaminases in the serum is 3 times higher than the upper limit of the norm, the dose of the drug should be reduced or discontinued.

In most cases, proteinuria decreases or disappears during therapy and does not indicate the onset or progression of an existing kidney disease. When combined with hypercholesterolemia and hypothyroidism or nephrotic syndrome, the treatment of major diseases should be performed prior to the beginning of treatment with rosuvastatin.

It is not recommended to use the drug jointly with HIV protease inhibitors (see section "Interaction with other drugs").With the use of some statins, especially for a long time, there have been reports of single cases of interstitial lung disease. Manifestations of the disease may be shortness of breath, unproductive cough and deterioration in overall health (weakness, weight loss and fever). If suspicion of interstitial lung disease should be stopped by statin therapy. 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.

Form release / dosage:

Tablets, film-coated, 10 mg, 20 mg.

Packaging:

For 10 tablets in a planar cell package.

1, 2, 3, 6, 9 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:At a temperature not exceeding 25 deg.

Shelf life:2 years.

Terms of leave from pharmacies:On prescription

Registration number:PL-000819

Date of registration:07.10.2011/07.04.2016

Expiration Date:07.10.2016

The owner of the registration certificate:PHARMSTANDART-TOMSKHIMFARM, OJSC PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-FORESTRY, OJSC Russia

PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Information update date: & nbsp06.07.2016

Illustrated instructions

Instructions

Acorta® (Akorta®)