Composition, form of production and packaging
The tablets covered with a film cover from light pink to pink color, round, biconcave, on a break from white to cream color.
rosuvastatin calcium 10.4 mg,
which corresponds to the content of rosuvastatin 10 mg
Excipients: lactose monohydrate (milk sugar) - 89.5 mg, microcrystalline cellulose - 29.82 mg, calcium hydrophosphate (E341) - 10.9 mg, crospovidone - 7.5 mg, magnesium stearate - 1.88 mg.
The composition of the shell: opedrai II 30K240001 pink (opadry II 30K240001 pink) (lactose monohydrate (sugar milk) - 2.4 mg, hypromellose (hydroxypropyl methylcellulose) 1.68 mg, titanium dioxide 1.413 mg, triacetin (glyceryl triacetate) 0.48 mg, iron oxide red - 0.027 mg) - 6 mg.
10 pieces. - Packings contour mesh (1) - packs cardboard.
10 pieces. - packings contour mesh (2) - packs cardboard.
10 pieces. - Packings contour mesh (3) - packs cardboard.
The tablets covered with a film cover from light pink to pink color, round, biconcave, on a break from white to cream color.
rosuvastatin calcium 20.8 mg,
which corresponds to the content of rosuvastatin 20 mg
Excipients: lactose monohydrate (sugar milk) - 179 mg, microcrystalline cellulose - 59.64 mg, calcium hydrophosphate (E341) - 21.8 mg, crospovidone - 15 mg, magnesium stearate - 3.76 mg.
The composition of the shell: opedrai II 30K240001 pink (opadry II 30K240001 pink) (lactose monohydrate (sugar milk) 4.8 mg, hypromellose (hydroxypropyl methylcellulose) 3.36 mg, titanium dioxide 2.826 mg, triacetin (glyceryl triacetate) 0.96 mg, iron oxide red - 0.054 mg) - 12 mg.
10 pieces. - Packings contour mesh (1) - packs cardboard.
10 pieces. - packings contour mesh (2) - packs cardboard.
10 pieces. - Packings contour mesh (3) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
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 to 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 LDL cholesterol, 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 (total cholesterol concentration minus the content of HDL-C ), Cholesterol-VLDL, TG-VLDL and increases the concentration of apolipoprotein A-I (ApoA-I). Rosuvastatin reduces the ratio of cholesterol-LDL / XC-HDL cholesterol, total cholesterol / cholesterol-HDL cholesterol, non-HDL cholesterol / cholesterol-HDL cholesterol, and Apov / ApoA-I.
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).
Absorption: Absolute bioavailability - 20%. The food reduces the suction speed. TC max - 3-5 h, after oral administration. Penetrates through the placental barrier.
Distribution: rosuvastatin is absorbed primarily 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: 10% of the dose is metabolized in the liver. Rosuvastatin is a non-core substrate for metabolism by enzymes of the cytochrome P450 system, CYP2C9 is the main isoenzyme involved in the metabolism of rosuvastatin, while the proenzymes CYP2C19, CYP3A4, and CYP2D6 are less involved in its metabolism.
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 not pharmacologically active.
Excretion: excreted mainly unchanged (90%) through the intestine (including absorbed and unabsorbed rosuvastatin); the remainder - kidneys. T 1/2 is approximately 19 hours. The half-life does not change with an increase in the 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, a membrane cholesterol transporter (transport protein C of organic anions) is involved in the hepatic capture of rosuvastatin, 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.
Pharmacokinetic studies showed approximately a twofold increase in the median AUC and C max of rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared to Europeans; the Indian patients showed an increase in the median AUC and C max by a factor of 1.3.Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics among Europeans and representatives of the Negroid race.
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.
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 T 1/2 of rosuvastatin; in 2 patients with points 8 and 9 on the Child-Pugh scale, the elongation T 1/2 which is 2 times higher than that for patients with a lower Child-Pugh score. Experience with the drug in patients with more severe impairment of liver function (above 9 on the Child-Pugh scale) is not available.
HMG-CoA reductase inhibitors, including rosuvastatin, bind to OATP1B1 transport proteins (the organic anion transport polypeptide involved in the capture of the HMG-CoA reductase inhibitor by hepatocytes) and BCRP (efflux transporter). In carriers of the genotypes SLCO1B1 (OATP1B1) p.521SS and / or ABCG2 (BCRP) p.421AA, there is a risk of increased exposure to rosuvastatin (AUC) compared to the carriers of the genotypes SLCO1B1 p.521TT and ABCG2 c.421CC.
- primary Fredriksen hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type lIb) as a supplement to the diet, when diet and other non-medicamentous treatments (eg exercise, weight loss) are insufficient;
- family homozygous hypercholesterolemia - as a supplement to diet and other lipid-lowering therapy (eg, LDL-apheresis) or in cases when such therapy is not effective enough;
- Hypertriglyceridemia (type IV but Fredriksenu) 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 IHD, but with an increased risk of its development (age over 50 for men and over 60 for women, increased concentration of 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, familial history of early onset of coronary artery disease).
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 taken inside, at any time of the day, regardless of food intake, without chewing and crushing the tablet, swallowing whole, washing down with water.
The recommended initial dose of rosuvastatin (unless indicated otherwise) is 10 mg 1 time per day for both patients who had 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 indivdualnym value of cholesterol and take into account the possible risk of cardiovascular complications, as well as 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 pharmacokinetic parameters in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin among Japanese and Chinese has been noted. 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 the use of all dosages of Acort 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 Chaid-Pugh scale is not available. The drug Acorta is contraindicated in patients with liver disease 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).
The increase in the exposure (AUC) to rosuvastatin was noted in carriers of genotypes SLCO1B1 (OAP1B1) c.521SS and ABCG2 (BCRP) c.421AA in comparison with carriers of the genotypes SLCO1B1 c.521TT and ABCG2 c.421S. For patients carrying genotypes c.521SS and c.421AA, 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 Nazis with factors that may indicate a predisposition to the development of myopathy.
Rosuvaetatin binds to various transport proteins (in particular, to OATP1B1 and BCRP). 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 Acorn should be assessed and the possibility of reducing its dose should be considered.
As with other inhibitors HMG-CoA reductase, 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 (> 1/10000 <1/1000); very rarely (<1/10000); frequency, unspecified (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 - reversible transient dose-dependent increase in 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; unspecified 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% of cases - for a dose of 40 mg). In most cases, proteinuria decreases or disappears and the process of therapy does not mean the emergence or development of an existing kidney disease; very rarely - hematuria.
Allergic reactions: infrequently - skin rash, itching, hives; rarely - angioedema; Unspecified frequency - Stevens-Johnson syndrome.
On the part of laboratory indicators: increased concentration in blood plasma glucose, bilirubin, increased activity of gamma-glutamyltranspeptidase, alkaline phosphatase. A dose-related increase in activity of creatine phosphokinase (CK) 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, ecchysomes, 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).
For the drug in a daily dose of 10 and 20 mg:
- hypersensitivity to rosuvastatin or any of the components of the drug;
- liver diseases in the active phase (including a persistent increase in the activity of "liver" transaminases, as well as any increase in the activity of "hepatic" transaminases in the blood serum more than 3 times compared with the upper limit of the norm);
- severe renal dysfunction (CC less than 30 ml / min);
- Lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose);
- simultaneous administration of cyclosporine;
- predisposition to miotoksicheskih complications;
- pregnancy, lactation;
- the use in women of childbearing age, not using reliable methods of contraception;
- the age of 18 years (effectiveness and safety have been established).
The daily dose of 40 mg (in addition to the above formulation is not suitable for contraindications):
- a personal or family history of muscle diseases;
- pas miotoksichnosti intake of other HMG-CoA reductase inhibitors or fibrates history;
- excessive use of alcohol;
- conditions that can lead to an increase in rosuvastatin plasma concentration;
- patients Mongoloid races;
- simultaneous administration of fibrates, renal insufficiency moderate severity (CC less than 60 ml / min).
For preparation at a daily dose of 10 and 20 mg: there is a risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, personal or family history of hereditary muscular disease and the previous history of muscle toxicity with other inhibitors of HMG-CoA reductase inhibitors or fibrates, excessive drinking, a condition in which there is an increase plasma concentrations of rosuvastatin, age over 65 years, history of liver disease, sepsis, hypotension, extensive surgery the intervention Twa, trauma, severe metabolic, endocrine or water-electrolyte disorders, uncontrolled epilepsy, race (Mongoloid race), concomitant use of fibrates.
For preparation at a daily dose of 40 mg: renal failure mild (CC 60 ml / min), age 65 years, a history of liver disease, septicemia, hypotension, extensive surgery, trauma, severe metabolic, endocrine, or electrolyte disorders aqueous or uncontrolled seizures.
PREGNANCY AND LACTATION
The drug is contraindicated during pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in patients with liver disease in active phase.
APPLICATION FOR CHILDREN
The drug is contraindicated in children under 18 years (effectiveness and safety have been established).
APPLICATION IN ELDERLY PATIENTS
Patients over the age of 65 years should be taken with caution.
Proteinuria, preferably of tubular origin was observed in patients with high doses of rosuvastatin, especially 40 mg, but in most cases has a periodic or transient. It is shown that this does not mean proteinuria of acute or progression of existing kidney disease. Patients taking the drug at a dose of 40 mg is recommended to monitor renal function during treatment.
Determining the activity of CK should not be carried out after intense exercise or when there are other possible reasons for the increased CPK, which can lead to misinterpretation of the results. With an increase in the initial activity of CK 5 times upper limit of normal in 5-7 days should be a re-measurement. Do not start treatment if the retest confirms the initial CK activity increased more than 5 times compared with the upper limit of normal.
In patients with existing risk factors for rhabdomyolysis is necessary to consider the balance of risk and the possible benefits of therapy and exercise clinical observation throughout the course of treatment.
It is necessary to inform the patient about the need for immediate medical attention messages about the sudden appearance of cases of muscle pain, muscle weakness or cramps, particularly in combination with malaise and fever.These patients should be monitored for the level of activity of CK. Therapy should be discontinued if CK activity increased more than 5 times in comparison with the upper limit of normal or if muscular symptoms are pronounced and cause daily discomfort (even if CK activity is 5 times less than the upper limit of normal). If the symptoms disappear and the activity of CK returns to normal, you should consider re-appointment of the drug or other inhibitors of HMG-CoA reductase in smaller doses with careful observation of the patient. Routine monitoring of CPK in the absence of symptoms of rhabdomyolysis impractical.
Very rare cases of immune-mediated necrotizing myopathy with clinical manifestations of persistent weakness of proximal muscle and increase CK activity in serum during treatment or discontinuation of statins, including rosuvastatin. You may need to conduct additional studies of muscle and nervous system, serology, and immunosuppressive agents therapy.
Reported an increase in the incidence of myositis and myopathy in patients taking other inhibitors of HMG-CoA reductase and combined with derivatives of fibric acid (including gemfibrozil), cyclosporin, nicotinic acid in the lipid-lowering doses (more than 1 g / day), azole antifungal agents, inhibitors HIV protease, and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with the appointment of some HMG-CoA reductase. Thus, without the simultaneous application of rosuvastatin and gemfibrozil. It must be carefully weighed risk ratio, and possible use in the combined use of rosuvastatin and fibrates or nicotinic acid as lipid-lowering doses. Medication contraindicated reception AKORT 40mg conjunction with fibrates.
AKORT The drug should not be administered to patients with acute, severe diseases, myopathy or suggestive with the possible development of renal failure secondary (sepsis, hypertension, surgery, trauma, metabolic syndrome, convulsions, endocrine disorders, water-electrolyte disturbances).
Preparation AKORT as other HMG-CoA reductase, should be taken with caution in patients who abuse alcohol or with a history of liver disease.
After 2-4 weeks after initiation of therapy and / or with an increase in dose needed AKORT control lipid metabolism (dose required correction if necessary).
It is recommended to determine the activity of "liver" transaminases before treatment and at 3 months after initiation of therapy. If the activity of "liver" in serum transaminases 3 times the upper limit of normal, dose should be reduced or stop taking.
In most cases, proteinuria decreases or disappears during therapy and does not imply the occurrence of acute or progression of existing kidney disease. With the combination of hypercholesterolemia and hypothyroidism or nephrotic syndrome underlying disease therapy should be conducted before the treatment with rosuvastatin.
Ne recommended joint use drug with HIV protease inhibitors ( "Interaction with other medicaments" see. Section). With some statins, especially for a long time, it was reported a few cases of interstitial lung disease. Manifestations of the disease may include dyspnea, nonproductive cough and general health deterioration (fatigue, weight loss and fever). For suspected interstitial lung disease should be discontinued statin therapy. Patients with a glucose concentration of from 5.6 to 6.9 mmol / l rosuvastatin therapy was associated with an increased risk of type 2 diabetes.
Symptoms: increased side effects. At simultaneous reception of several daily doses of rosuvastatin pharmacokinetic parameters are not changed.
Treatment: No specific antidote. It is recommended that symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. Necessary to monitor liver function and creatine kinase activity. Hemodialysis is ineffective.
Effect of using other medications for rosuvastatin
inhibitors transport proteins: rosuvastatin binds to certain transport proteins, in particular with OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins can be accompanied by an increase in rosuvastatin plasma concentrations and an increased risk of myopathy.
Rosuvastatin did not affect the plasma concentration of cyclosporine. Cyclosporin enhances the effect of rosuvastatin (slows its excretion, AUC increases by 7 times, C max is 11 times).
Gemfibrozil rosuvastatin effect enhances (increases its C maxand AUC 2 times). Gemfibrozil, fenofibrate and other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g / day) increase the risk of myopathy while the use of inhibitors of HMG-CoA reductase, perhaps due to the fact that they can cause myopathy when used as monotherapy.
Taking the drug at a dose of 40 mg is contraindicated when coadministered with fibrates. When assigning gemfibrozil rosuvastatin dose should not exceed 10 mg / day.
Although the exact mechanism of the interaction is unknown, co-administration of HIV protease inhibitors can cause a considerable increase rosuvastatin exposure. Pharmacokinetic study on the simultaneous use of 20 mg of rosuvastatin with a combined preparation comprising two HIV-protease inhibitor (400 mg lopinavir / ritonavir 100 mg) in healthy volunteers resulted in approximately two-fold and five-fold increase in AUC (0-24) and C max of rosuvastatin respectively. Therefore it is not recommended simultaneous rosuvastatin and inhibitors of HIV proteases.
Antacids containing aluminum and magnesium ions, lead to a decrease in plasma concentrations of rosuvastatin about 50% (antacids should be used within 2 hours after taking rosuvastatin, the clinical significance of this interaction is not known). Erythromycin enhances motility gastrointestinal tract, resulting in reduced effect of rosuvastatin (AUC reduces it by 20% and C max by 30%).
The results of studies in vivo and in vitro showed that rosuvastatin is neither an inhibitor or inducer of P450 isoenzyme cytochrome. Furthermore, rosuvastatin is a non-core substrate for these enzymes, there was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4), and ketoconazole (CYP2A6 inhibitor and a CYP3A4). The combined use of rosuvastatin and itraconazole (CYP3A4 inhibitor) rosuvastatin AUC increases by 28% (clinically insignificant). Thus it is not expected interaction associated with metabolism by cytochrome P450.
The simultaneous use of rosuvastatin in a dose of 10 mg of ezetimibe and 10 mg was accompanied by an increase in AUC of rosuvastatin in patients with hypercholesterolemia. However, we can not exclude the pharmacodynamic interaction between rosuvastatin and ezetimibe that can cause adverse effects.
Interaction with drugs that require correction doses of rosuvastatin (see. Table 1)
The dose should be adjusted rosuvastatin combined use with drugs, if necessary, increasing its exposure. It should also be corrected maximum daily dose so that the expected exposure rosuvastatin not greater than that for a 40 mg dose received without simultaneous administration of drugs interacting with rosuvastatin.
Table 1. Effect of combined use of drugs on rosuvastatin exposure (AUC, in descending order of magnitude) according to published clinical studies
Dosage Dosage of concomitant medications rosuvastatin Exposure Change rosuvastatin (AUC)
Cyclosporin 75 mg twice daily and 200 mg twice day, 6 months 10 mg once a day, 10 days, an increase of 7.1 times
atazanavir 300 mg / ritonavir 100 mg once a day and 8 days 10 mg, once to increase 3.1 times
Lopinavir 400 mg / 100 mg ritonavir twice day, 17 days, 20 mg once a day, 7 days, an increase of 2.1 times
Gemfibrozil 600 mg twice a day, 7 days 80 mg, once to increase 1.9 times
Eltrombopag 75 mg once a day, 10 days, 10 mg, once to increase 1.6 times
Darunavir 600 mg / 100 mg ritonavir twice per day, 7 days 10 mg once a day, 7 days, an increase of 1.5 times
tipranavir 500 mg / 200 mg ritonavir twice per day, 11 days, 10 mg, once to increase 1.4 times
Dronedarone 400 mg twice a day unknown increase 1.4 times
Itrokonazol 200 mg once a day, 5 days of 10 mg mono- increase 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 700mg / 100 mg ritonavir twice per day 8 days 10 mg, once unchanged
Aleglitazar 0.3 mg, 40 mg 7 days, 7 days without change
Silymarin 140 mg three times a day, 5 days of 10 mg, once unchanged
Fenofibrate 67 mg three times a day, 7 days, 10 mg, 7 days without change
Rifampin 450 mg once a day, 7 days 20 mg, once unchanged
ketoconazole 200 mg twice a day, 7 days 80 mg, once unchanged
Fluconazole 200 mg once a day, 11 days, 80 mg, once unchanged
Erythromycin 500 mg 4 times a day, 7 days 80 mg, once a decrease of 28%
baicalin 50 mg three times a day, 14 days, 20 mg, once a 47% reduction
effect of applying rosuvastatin on other drugs
Initiation of therapy with rosuvastatin or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (eg, warfarin), may result in an increase in prothrombin time (an increase in the international normalized ratio (MHO)). Cancel rosuvastatin or reducing the dose may reduce the MHO (in such cases MHO monitoring).
Rosuvastatin enhances the effect of oral contraceptives (AUC increases ethinyl estradiol and norgestrel for 26% and 34%, respectively, which should be considered when selecting a dose oral contraceptives). Pharmacokinetic data but the simultaneous use of rosuvastatin and hormone replacement therapy are not available, therefore, one can not exclude a similar effect when using this combination.
Not expected clinically significant interactions of rosuvastatin with digoxin.