Rosuvastatin FT tablets

Name:
Rosuvastatin ft Release form film-coated tablets Dosage 5 mg Quantity per pack 30 pcs. ProducerPharmtekhnologiya Ltd. MNNRozuvastatin FTGGipolipidemic agent – hmg-coa reductase inhibitor
Description:
Dosage 5 mg: round, biconvex, film-coated pink tablets. Dosage 10 mg: round, biconvex, scored on one side, pink film-coated tablets. Dosage 20 mg: round, biconvex, pink film-coated tablets. Composition Each film-coated tablet contains: tablet core: – active ingredient: rosuvastatin (as rosuvastatin calcium) – 5.0 mg*, or 10.0 mg**, or 20.0 mg***; – excipients: microcrystalline cellulose, crospovidone, povidone, magnesium stearate, lactose monohydrate; tablet shell: lactose monohydrate, hypromellose, triacetin, titanium dioxide, iron oxide red. * – equivalent to the content of 5.2 mg of rosuvastatin calcium ** – equivalent to the content of 10.4 mg of rosuvastatin calcium *** – equivalent to the content of 20.8 mg of rosuvastatin calcium Pharmacotherapeutic group Hypolipidemic drugs. HMG-CoA reductase inhibitors. ATX code: C10AA07. Pharmacological properties Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase. HMG-CoA reductase is a rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate. Mevalonate is a cholesterol precursor. The main site of action of rosuvastatin is the liver, which is a target organ for lowering the concentration of cholesterol in the blood. Rosuvastatin increases the number of hepatic LDL receptors on the cell surface, thus stimulating the uptake and catabolism of LDL. Rosuvastatin also inhibits the synthesis of VLDL in the liver, thereby reducing the total number of VLDL and LDL particles. Rosuvastatin reduces elevated concentrations of LDL cholesterol, total cholesterol and triglycerides and increases the concentration of HDL cholesterol. Also, rosuvastatin reduces the content of ApoB, non-HDL-cholesterol, VLDL cholesterol, VLDL triglycerides and increases the level of ApoA-I. Rosuvastatin reduces the ratio of LDL cholesterol / HDL cholesterol, total cholesterol / HDL cholesterol, non-HDL-cholesterol / HDL-cholesterol and ApoB / ApoA-I. The therapeutic effect is manifested within the first week from the start of taking the drug. 90% of the maximum possible response is achieved within 2 weeks. The maximum possible response is usually achieved by the 4th week of taking rosuvastatin and then maintained at the achieved level with further drug administration. ROSUVASTATIN FT is effective in adults with hypercholesterolemia with or without triglyceridemia, regardless of race, sex, age, and in such special categories of patients as patients with diabetes mellitus and patients with familial hypercholesterolemia. Rosuvastatin is extensively taken up by the liver, which is the main site for cholesterol synthesis and LDL cholesterol clearance. The systemic exposure of rosuvastatin increases in proportion to the dose. When taking rosuvastatin several times a day, no changes in pharmacokinetic parameters are observed. There was no clinically significant effect of age or gender on the pharmacokinetics of rosuvastatin in adults. Pharmacokinetic studies demonstrate an approximately 2-fold increase in median AUC and Cmax in patients of Asian origin (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with those in Caucasians; in Southeast Asians, an increase in median AUC and Cmax by approximately 1.3 times was noted. Population pharmacokinetic analysis did not reveal clinically significant differences in the pharmacokinetics of rosuvastatin in Caucasians, representatives of Latin America, the Caribbean, and people of African descent. In a study in patients with varying degrees of impaired renal function, mild to moderate renal disease had no effect on plasma concentrations of rosuvastatin or its N-desmethyl metabolite. In patients with severe renal impairment (creatinine clearance less than 30 ml / min), a 3-fold increase in the concentration of rosuvastatin in blood plasma and a 9-fold increase in the concentration of the N-desmethyl metabolite were observed compared with healthy volunteers. Steady-state plasma concentrations of rosuvastatin in patients undergoing hemodialysis were approximately 50% higher than in healthy volunteers. In a study in patients with varying degrees of hepatic impairment, there was no evidence of an increase in rosuvastatin exposure in patients with a Child-Pugh score of 7 or less. Two patients with scores of 8 and 9 experienced an increase in systemic exposure of at least 2-fold compared with patients who scored lower. There are no data on the features of the pharmacokinetics of rosuvastatin in patients with a score of more than 9 according to the Child-Pugh criteria, since there is no experience in this category of patients. The pharmacokinetics of HMG-CoA reductase inhibitors, including rosuvastatin, involve transport proteins OATP1B1 and BCRP. Patients with SLCO1B1 (OATP1B1) and/or ABCG2 (BCRP) genetic polymorphisms are at risk of increased exposure to rosuvastatin. The individual polymorphisms SLCO1B1 c.521CC and ABCG2 c.421AA are associated with increased exposure (AUC) of rosuvastatin compared to the genotypes SLCO1B1 c.521TT or ABCG2 c.421CC. This specific genotyping has not been implemented in clinical practice protocols, however, patients who are known to have these types of polymorphisms are advised to prescribe a lower daily dose of rosuvastatin. Pharmacokinetic studies involving children and adolescents 10-17 and 6-17 years old with heterozygous familial hypercholesterolemia have shown that the exposure of rosuvastatin in children and adolescents is comparable or less than that in adult patients. Indications for use 1. Treatment of hypercholesterolemia – primary hypercholesterolemia (type IIa, including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (type IIb) in adults, adolescents, and children 6 years of age and older as an adjunct to diet when the effect of diet and other non-drug treatments (eg, exercise, weight loss) is insufficient; Homozygous familial hypercholesterolemia in adults, adolescents, and children aged 6 years and older as an adjunct to diet and other lipid-lowering therapies (eg, LDL apheresis), or when such therapies do not work as expected effect. 2. Primary prevention of cardiovascular disease Primary prevention of severe cardiovascular disease (stroke, myocardial infarction, diseases requiring arterial revascularization) in patients without clinical evidence of coronary heart disease (CHD) who are considered to be at increased risk development of cardiovascular disease (age men ≥ 50 years and age women ≥ 60 years, concentration of highly sensitive C-reactive protein (hsCRP) ≥ 2 mg/l and the presence of at least one of the additional risk factors for the development of cardiovascular disease, such as hypertension, low HDL cholesterol, smoking, or early development of CAD in family members). Dosage and administration Before starting the use of the drug ROSUVASTATIN FT, the patient should be prescribed a standard diet aimed at lowering cholesterol levels. This diet should be followed throughout the entire period of therapy with rosuvastatin. The dose of the drug should be adjusted individually depending on the goal of therapy and the patient’s response to the drug, taking into account current generally accepted recommendations for target lipid levels and patient management. ROSUVASTATIN FT should be taken once a day. The tablet should be swallowed whole without chewing and washed down with water. ROSUVASTATIN FT can be taken at any time of the day, regardless of meals. It is advisable to take the tablet at the same time every day. Treatment of hypercholesterolemia The recommended starting dose of ROSUVASTATIN FT is 5 mg or 10 mg once daily for both patients who have not previously taken statins and for patients who are switched to rosuvastatin after using another HMG-CoA reductase inhibitor. When choosing an initial dose, individual cholesterol levels, the predicted risk of cardiovascular disease, and the potential risk of developing adverse reactions should be taken into account (see the “Side effect” section). Dose adjustment upwards under the control of lipid metabolism can be made after 4 weeks from the start of the current dose, if necessary; this is due to the fact that the maximum possible effect when taking rosuvastatin at a certain dose is usually achieved by the 4th week of therapy and is maintained at the achieved level with further use of the drug (see section “Pharmacological properties”). When using a dose of 40 mg, there is a higher frequency of reports of adverse reactions than when using lower doses (see section “Side Effects”). Therefore, final titration up to the maximum daily dose (40 mg) should only be considered in patients with severe hypercholesterolemia associated with high CV risk (particularly in patients with familial hypercholesterolemia) who fail to achieve their individual therapy goals with taking the drug at a dose of 20 mg and for which regular routine medical supervision can be carried out (see section “Special instructions and precautions”). At the start of the 40 mg dose, a doctor’s supervision is recommended. Prevention of cardiovascular disease In a study to reduce the risk of cardiovascular disease, rosuvastatin was used at a dose of 20 mg per day. Children and adolescents The appointment of rosuvastatin to children and adolescents should be made only by qualified specialists. Children and adolescents aged 6 to 17 years (Tanner stage 70 years is 5 mg (see section “Special Instructions and Precautions”). No other dose adjustment is required due to age. Patients with renal insufficiency Dose adjustment in patients with Mild to moderate renal impairment is not required.The recommended starting dose for patients with moderate renal impairment (creatinine clearance < 60 ml/min) is 5 mg. The 40 mg dose is contraindicated in patients with moderate renal impairment. The use of the drug ROSUVASTATIN FT at any dose is contraindicated in patients with severe renal impairment (see sections "Contraindications" and "Pharmacological properties"). Patients with impaired liver function There was no increase in systemic exposure of rosuvastatin in patients with a Child criteria - I drink 7 or less.However, an increase in systemic exposure was observed b in patients with a Child-Pugh score of 8 and 9 (see section "Pharmacological properties"). In these patients, an assessment of liver function should be carried out (see section "Special instructions and precautions"). There is no experience of use in patients with a score of more than 9 according to the Child-Pugh criteria. ROSUVASTATIN FT is contraindicated in patients with active liver disease (see section "Contraindications"). Race An increase in the systemic exposure of rosuvastatin is observed in patients of Asian origin (see sections "Contraindications", "Special instructions and precautions", "Pharmacological properties"). The recommended starting dose for patients in this group is 5 mg. The 40 mg dose is contraindicated in Asian patients. Genetic polymorphisms Special types of genetic polymorphisms are known that can lead to an increase in the exposure of rosuvastatin (see the section "Pharmacological properties"). For patients known to have these specific types of polymorphisms, a lower daily dose of ROSUVASTATIN FT is recommended. Patients with factors predisposing to the development of myopathy The recommended starting dose for patients with factors predisposing to the development of myopathy is 5 mg (see section "Special Instructions and Precautions"). The 40 mg dose is contraindicated in some of these patients (see Contraindications section). Concomitant drug therapy Rosuvastatin is a substrate for various transport proteins (eg, OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when ROSUVASTATIN FT is co-administered with certain medicinal products that may increase plasma concentrations of rosuvastatin due to interactions with these transport proteins (eg, cyclosporine and certain protease inhibitors, including combinations of ritonavir with atazanavir, lopinavir and / or tipranavir; see sections "Special instructions and precautions", "Interaction with other medicinal products and other forms of interaction"). Whenever possible, consideration should be given to prescribing alternative medicinal products and, if necessary, consider temporarily discontinuing rosuvastatin therapy. In situations where the co-administration of these drugs and rosuvastatin cannot be avoided, the benefit / risk ratio of concurrent therapy and the need for dose adjustment of the drug ROSUVASTATIN FT should be carefully assessed (see section "Interaction with other drugs and other forms of interaction"). If you have taken a higher dose of rosuvastatin than was prescribed to you by your doctor, you should seek advice from your doctor or the nearest medical facility. When you are hospitalized and / or when you are being treated for any other disease / pathological condition, you must inform the medical staff that you are currently taking rosuvastatin. Don't worry if you miss your next dose of rosuvastatin; take your next scheduled dose at the usual time. It is not allowed to take a double dose in order to compensate for the missed one! If you wish to temporarily suspend / stop therapy with rosuvastatin, you must first notify your doctor and follow his recommendations. When therapy with rosuvastatin is discontinued, cholesterol levels may rise again. Side effects Side effects observed with the use of rosuvastatin, as a rule, are mild and temporary. Adverse reactions that may occur with the use of rosuvastatin are classified by frequency of occurrence and by organ systems. The frequency of occurrence of side effects is estimated according to the following scheme: very often (≥ 1/10); often (≥ 1/100 to < 1/10); infrequently (≥ 1/1000 to < 1/100); rarely (≥ 1/10,000 to < 1/1,000); very rarely (< 1/10000); unknown (frequency cannot be estimated from the available data). Blood and lymphatic system disorders: rarely - thrombocytopenia. Immune system disorders: rarely - hypersensitivity reactions, including angioedema. Endocrine system disorders: often - diabetes mellitus (frequency will depend on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol / l, body mass index > 30 kg / m2, increased triglycerides, history of hypertension)) . Mental disorders: unknown – depression. Nervous system disorders: often – headache, dizziness; very rarely – polyneuropathy, memory loss; unknown – peripheral neuropathy, sleep disturbances, including insomnia and nightmares. Respiratory, thoracic and mediastinal disorders: unknown – cough, shortness of breath. Gastrointestinal disorders: often – constipation, nausea, abdominal pain; rarely – pancreatitis; unknown – diarrhea. On the part of the liver and biliary tract: rarely – an increase in the levels of hepatic transaminases; very rarely – jaundice, hepatitis. Skin and subcutaneous tissue disorders: infrequently – itching, rash, urticaria; unknown – Stevens-Johnson syndrome. Musculoskeletal and connective tissue disorders: often – myalgia; rarely – myopathy (including myositis), rhabdomyolysis; very rarely – arthralgia; unknown – tendon disorders, which are sometimes complicated by ruptures, immune-mediated necrotizing myopathy. Renal and urinary tract disorders: very rarely – hematuria. Violations of the genital organs and mammary gland: very rarely – gynecomastia. General disorders and disorders at the injection site: often – asthenia; unknown – edema. As with other HMG-CoA reductase inhibitors, the frequency of adverse reactions generally depends on the dose of rosuvastatin. Effects on the kidneys Proteinuria, identified by dipstick analysis and mainly of tubular origin, has been observed in patients treated with rosuvastatin. Changes in urinary protein content from none or traces to ++ or more were noted in less than 1% of patients at separate intervals during the use of rosuvastatin at doses of 10 mg and 20 mg and in approximately 3% of patients taking rosuvastatin at a dose of 40 mg. A slight increase in protein content (from none or traces to a value of +) was observed at a dose of 20 mg. In most cases, proteinuria decreases or disappears spontaneously during ongoing therapy. A review of currently available clinical trial data and post-marketing observations found no causal relationship between proteinuria and acute or progressive kidney disease. Hematuria has been observed in some patients treated with rosuvastatin, but data from clinical studies indicate that the incidence of hematuria is low. Effects on skeletal muscle Pathological events from the skeletal muscle, in particular, myalgia, myopathy (including myositis) and, in rare cases, rhabdomyolysis with or without the development of acute renal failure have been reported in patients taking rosuvastatin at any dose, especially at doses greater than 20 mg. A dose-dependent increase in creatine kinase levels was observed in patients taking rosuvastatin. In most cases, this rise was minor, asymptomatic and transient. If the level of creatine kinase has increased (to a value more than 5 times the upper limit of normal), treatment should be discontinued (see section “Special instructions and precautions”). Effects on the liver As with other HMG-CoA reductase inhibitors, a dose-dependent increase in transaminase levels was observed in a small number of patients taking rosuvastatin. In most cases, this rise was minor, asymptomatic and transient. Other reactions The following side effects have been reported with some statins: – sexual dysfunction; – in isolated cases – interstitial lung disease, especially with prolonged use of the drug (see section “Special instructions and precautions”). The frequency of reports of rhabdomyolysis, severe impairment of kidney or liver function (manifested mainly in the form of increased activity of hepatic transaminases) is higher with the use of rosuvastatin at a dose of 40 mg. Children and adolescents Increases in creatine kinase levels greater than 10 times the upper limit of normal and muscle symptoms after exercise or increased physical activity were observed more often in children and adolescents compared with adults (see section “Special Instructions and Precautions”). Otherwise, the safety profile of rosuvastatin in children and adolescents was similar to that in adults. If you experience one or more of these adverse reactions, as well as reactions not listed in this section of the package leaflet, you should consult a doctor. Reporting adverse reactions If you experience any adverse reactions, it is recommended that you consult your doctor. This recommendation applies to any possible adverse reactions, including those not listed in the package insert for the use of the medicinal product. You can also report adverse reactions to the Adverse Drug Reactions Information Database. By reporting adverse reactions, you help to get more information about the safety of the medicine. Contraindications Contraindications to the use of the drug ROSUVASTATIN FT are: – known individual hypersensitivity to rosuvastatin and / or to any of the excipients that make up the drug; – liver disease in the active phase, including an unexplained, persistent increase in serum transaminase levels and any increase in serum transaminase levels greater than 3 times the upper limit of normal; – severe renal impairment (creatinine clearance < 30 ml/min); - myopathy; - concomitant use of cyclosporine; - period of pregnancy; - the period of breastfeeding; - childbearing age in women not taking appropriate contraceptive measures. The 40 mg dose is contraindicated in patients with predisposing factors for myopathy/rhabdomyolysis. The group of such factors includes: - moderately severe impairment of kidney function (creatinine clearance < 60 ml/min); - hypothyroidism; - the presence in a personal or family history of hereditary muscular pathology; - a history of manifestations of myotoxicity while taking another inhibitor of HMG-CoA reductase or fibrate; - alcohol abuse; - age over 70 years; - situations in which an increase in the concentration of rosuvastatin in the blood plasma is possible; - Asian origin; - concomitant use of fibrates. (See sections "Special instructions and precautions", "Interaction with other medicinal products and other forms of interaction", "Pharmacological properties"). Overdose There is no specific treatment in case of overdose. In case of overdose, the patient should receive symptomatic and supportive treatment. Liver function and creatine kinase levels should be monitored. It is unlikely that hemodialysis will be of significant benefit in this case. Interaction with other drugs and other forms of interaction Effect of co-administered drugs on rosuvastatin Inhibitors of transport proteins Rosuvastatin is a substrate for several transport proteins, including the transport protein OATP1B1, which is responsible for the uptake and movement of substances into the liver cells, and the efflux transport protein BCRP. The simultaneous use of rosuvastatin and drugs that inhibit these transport proteins can lead to an increase in the concentration of rosuvastatin in the blood plasma and, thereby, to an increase in the risk of developing myopathy (see sections "Method of application and doses", "Special instructions and precautions" , table 1 in the section "Interaction with other medicinal products and other forms of interaction"). Cyclosporine During the period of simultaneous use of rosuvastatin and cyclosporine, the AUC values of rosuvastatin were on average 7 times higher than those observed in healthy volunteers (see table 1). Rosuvastatin is contraindicated in patients taking cyclosporine (see section "Contraindications"). Simultaneous use does not affect the concentration of cyclosporine in plasma. Protease inhibitors Although the exact mechanism of interaction is unknown, the simultaneous use of a protease inhibitor and rosuvastatin can significantly increase the exposure of rosuvastatin (see table 1). For example, in a pharmacokinetic study, the simultaneous use of 10 mg rosuvastatin and a combination drug containing two protease inhibitors (300 mg atazanavir/100 mg ritonavir) in healthy volunteers was accompanied by an approximately 3-fold increase in AUC of rosuvastatin and an approximately 7-fold increase in Cmax of rosuvastatin. The combined use of the drug ROSUVASTATIN FT and certain combinations of protease inhibitors can only be carried out after careful consideration of the need to adjust the dose of rosuvastatin, based on the expected increase in exposure to rosuvastatin (see sections "Method of administration and doses", "Special instructions and precautions", table 1 in the section "Interaction with other medicinal products and other forms of interaction"). Gemfibrozil and other lipid-lowering agents The simultaneous use of rosuvastatin and gemfibrozil led to an increase in AUC and Cmax of rosuvastatin by 2 times (see section "Special instructions and precautions"). Based on data from specific drug interaction studies, a pharmacokinetically significant interaction between rosuvastatin and fenofibrate should not be expected, but a pharmacodynamic interaction may occur. Gemfibrozil, fenofibrate, other fibrates and niacin (nicotinic acid) at lipid-lowering doses (greater than or equal to 1 g/day) increase the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors. This is probably due to the fact that these drugs can cause myopathy when used as monotherapy. It is forbidden to take rosuvastatin at a dose of 40 mg simultaneously with fibrates (see sections "Contraindications", "Special instructions and precautions"). Patients who are taking any drugs from the fibrate group should start taking the drug ROSUVASTATIN FT at a dose of 5 mg. Ezetimibe The simultaneous use of rosuvastatin at a dose of 10 mg and ezetimibe at a dose of 10 mg in patients with hypercholesterolemia led to an increase in the AUC of rosuvastatin by 1.2 times (see table 1). The possibility of a pharmacodynamic interaction between rosuvastatin and ezetimibe, leading to the development of side effects, cannot be excluded (see section "Special Instructions and Precautions"). Antacids Simultaneous administration of rosuvastatin with an antacid suspension containing aluminum hydroxide and magnesium hydroxide resulted in a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect weakened when taking an antacid 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied. Erythromycin The simultaneous use of rosuvastatin and erythromycin led to a decrease in the AUC and Cmax of rosuvastatin: the AUC value decreased by 20%, Cmax - by 30%. This interaction may be due to increased motility of the gastrointestinal tract due to the action of erythromycin. Enzymes of the cytochrome P450 system The results of in vitro and in vivo studies demonstrate that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Moreover, rosuvastatin is an unsuitable substrate for these isoenzymes. Therefore, drug interactions that are associated with metabolism mediated by cytochrome P450 enzymes are not predicted. There were no clinically significant interactions between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) and between rosuvastatin and ketoconazole (an inhibitor of CYP2A6 and CYP3A4). Interactions Requiring Rosuvastatin Dose Adjustment (See also Table 1) If ROSUVASTATIN FT is to be co-administered with other medicinal products that increase rosuvastatin exposure, the dose of rosuvastatin should be adjusted. Treatment with rosuvastatin should be initiated at a dose of 5 mg once daily if an increase in exposure (AUC) of rosuvastatin by approximately 2-fold or more is expected. The maximum daily dose of rosuvastatin should be adjusted so that, with a high degree of probability, the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg / day, which is taken without drugs that interact with rosuvastatin. For example, when used with gemfibrozil, the maximum daily dose of rosuvastatin will be 20 mg (increase in exposure by 1.9 times), when used with a combination of ritonavir / atazanavir - 10 mg (increase in exposure by 3.1 times). Table 1. Effect of co-administered medicinal products on rosuvastatin exposure (AUC; in descending order of magnitude) according to clinical trial data. Concomitant drug dosing regimen Rosuvastatin dosing regimen Rosuvastatin AUC change* Cyclosporine 75-200 mg twice daily for 6 months 10 mg once daily for 10 days ↑ 7.1 times Atazanavir 300 mg/ritonavir 100 mg once daily for 8 days 10 mg single dose ↑ 3.1 times Simeprevir 150 mg once daily 7 days 10 mg single dose ↑ 2.8 times Lopinavir 400 mg/ritonavir 100 mg twice daily for 17 days 20 mg once daily for 7 days ↑ 2 ,1 times Clopidogrel 300 mg, then 75 mg 24 hours later 20 mg once a day ↑ 2.0 times Gemfibrozil 600 mg twice a day for 7 days 80 mg once a day ↑ 1.9 times Eltrombopag 75 mg once a day for 5 days 10 mg once ↑ 1.6 times Darunavir 600 mg/ritonavir 100 mg twice daily for 7 days 10 mg once daily, 7 days ↑ 1.5 times Tipranavir 500 mg/ritonavir 200 mg twice daily for 11 days 10 mg once ↑ 1 ,4 times Dronedarone 400 mg twice daily Unknown ↑ 1.4 times Itraconazole 200 mg once daily for 5 days 10 mg once daily ↑ 1.4 times ** Ezetimibe 10 mg once daily and 14 days 10 mg once daily 14 days ↑ 1.2 times ** Fosamprenavir 700 mg/ritonavir 100 mg twice daily 8 days 10 mg once No change Aleglitazar 0.3 mg 7 days 40 mg 7 days No change Silymarin 140 mg 3 times a day 5 days 10 mg once No change Fenofibrate 67 mg 3 times a day 7 days 10 mg 7 days No change Rifampin 450 mg 1 time per day 7 days 20 mg once No change Ketoconazole 200 mg 2 times a day 7 days 80 mg single dose No change Fluconazole 200 mg once a day for 11 days 80 mg once No change Erythromycin 500 mg 4 times a day for 7 days 80 mg once ↓ 20% Baicalin 50 mg 3 times a day for 14 days 20 mg once a day ↓ 47% * Data , presented as x-fold change, represent a simple ratio between the use of rosuvastatin in combination and rosuvastatin in monotherapy. The data presented as % change represent the % difference compared to the values when using rosuvastatin as monotherapy. An increase is indicated by a ↑, no change by a ↔, a decrease by a ↓. ** Several interaction studies have used different dosing regimens for rosuvastatin. Table 1 shows the most significant ratio. Effects of rosuvastatin on concomitant medicinal products Vitamin K antagonists As with other HMG-CoA reductase inhibitors, when starting rosuvastatin or adjusting its dose upwards in patients receiving concomitant vitamin K antagonists (eg, warfarin or other coumarin anticoagulant ), possibly increasing the international normalized ratio (INR). Stopping taking rosuvastatin or adjusting the dose of the drug downwards may lead to a decrease in INR. In such situations, proper monitoring of INR is required. Oral contraceptives / hormone replacement therapy (HRT) The simultaneous use of rosuvastatin and an oral contraceptive resulted in an increase in the AUC of ethinylestradiol and norgestrel by 26% and 34%, respectively. An increase in plasma concentrations should be taken into account when selecting doses of oral contraceptives. There are no data on pharmacokinetics in individuals who simultaneously take rosuvastatin and HRT, so the occurrence of a similar effect cannot be ruled out. At the same time, this combination has been widely used in women in clinical trials and was well tolerated by them. Other medicines Digoxin According to specific drug interaction studies, no clinically significant interaction between rosuvastatin and digoxin is expected. Fusidic acid No interaction studies have been conducted with rosuvastatin and fusidic acid. The risk of myopathy, including rhabdomyolysis, may be increased by concomitant use of systemic fusidic acid and statins. The mechanism of interaction (pharmacodynamic and / or pharmacokinetic interaction) is currently unknown. Cases of rhabdomyolysis (including fatal cases) have been reported in patients treated concomitantly with fusidic acid and a statin. In patients in whom the use of systemic fusidic acid is considered necessary, statin therapy should be interrupted for the period of fusidic acid use (see section "Special Instructions and Precautions"). Children Drug interaction studies have only been performed in adults. The interaction profile in children is unknown. Special instructions and precautions Effects on the kidneys Prot