rosuvastatin | Rosuvastatin-SZ tablets coated. 20 mg 30 pcs. pack
Special Price
$21.56
Regular Price
$29.00
In stock
SKU
BID481627
Latin name
Rosuvastatin
Rosuvastatin
Latin name
Rosuvastatin
Release form
Tablets, film-coated, pink, round, biconvex in cross section, the core of a tablet is white or almost white vet.
Packing
10 pcs - blister packs (3) - packs of cardboard.
Pharmacological action
Pharmacotherapeutic group of the drug: lipid-lowering agent - HMG-CoA reductase inhibitor
ATX code: [C10AA07]
Pharmacological properties of
Pharmacodynamics
Mechanism of action of
Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase 3 enzyme, 3 enzyme mevalonic acid, a precursor to cholesterol. The main target of the action of rosuvastatin is the liver, where the synthesis of cholesterol (cholesterol) and the catabolism of low density lipoproteins (LDL) are carried out. Rosuvastatin increases the number of “liver” LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of very low density lipoproteins (VLDL), thereby reducing the total amount of LDL and VLDL.
Pharmacodynamics
Rosuvastatin-SZ reduces elevated concentrations of LDL cholesterol (cholesterol-LDL), total cholesterol, triglycerides (TG), increases the concentration of high-density lipoprotein cholesterol (HDL-cholesterol), and also reduces the concentration of apolipoprotein B non-HDL, cholesterol-VLDL, TG-VLDLP and increases the concentration of apolipoprotein A-I (ApoA-I), reduces the ratio of cholesterol-LDL / cholesterol-HDL, total cholesterol-cholesterol-HDL and cholesterol-HDL / cholesterol-HDL and the ratio of apoV / ApoA-I. The therapeutic effect develops within one week after the start of therapy with the drug Rosuvastatin-SZ, after 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with regular use of the drug. Rosuvastatin-SZ is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender or age, including patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with type IIa and IIb hypercholesterolemia according to Fredrickson (the average initial concentration of LDL-C is about 4.8 mmol / L) when taking the drug at a dose of 10 mg, the concentration of LDL-C reaches less than 3 mmol / L. In patients with heterozygous familial hypercholesterolemia, receiving Rosuvastatin-SZ at a dose of 20-80 mg, there is a positive dynamics in the lipid profile. After titration to a daily dose of 40 mg (12 weeks of therapy), a decrease in the concentration of LDL-C by 53% is noted. In 33% of patients, an LDL-C concentration of less than 3 mmol / L is achieved. In patients with homozygous familial hypercholesterolemia, taking Rosuvastatin-SZ at a dose of 20 mg and 40 mg, the average decrease in the concentration of LDL-C is 22%. In patients with hypertriglyceridemia with an initial TG concentration from 273 to 817 mg / dl, treated with Rosuvastatin-SZ at a dose of 5 mg to 40 mg once a day for 6 weeks, the concentration of TG in the blood plasma was significantly reduced. An additive effect is observed in combination with fenofibrate in relation to the content of triglycerides and with nicotinic acid in lipid lowering doses in relation to the content of HDL-C (see also the section “Special Instructions”). According to the results of clinical studies, patients with severe hypercholesterolemia and a high risk of cardiovascular disease (CVD) should be prescribed a dose of 40 mg of Rosuvastatin-SZ. The results of a clinical study (The rationale for using statins for primary prevention: an interventional study evaluating rosuvastatin) showed that rosuvastatin significantly reduced the risk of developing cardiovascular complications.
Pharmacokinetics
Absorption and distribution of
The maximum concentration of rosuvastatin in blood plasma is reached approximately 5 hours after ingestion. Absolute bioavailability is approximately 20%. Rosuvastatin is metabolized mainly by the liver, which is the main site of cholesterol synthesis and metabolism of LDL-C. The volume of distribution of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.
Metabolism
Undergoes limited metabolism (about 10%). Rosuvastatin is a non-core substrate for metabolism by enzymes of the cytochrome P450 system. The main isoenzyme involved in the metabolism of rosuvastatin is the isoenzyme CYP2C9. The isoenzymes СYР2С19, СЫРЗА4, and CYP2D6 are less involved in metabolism. The main identified metabolites of rosuvastatin are N-desmethyltrosluvuvastatin and lactone metabolites. N-desmethylrozuvastatin is approximately 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is metabolites.
Excretion of
About 90% of the dose of rosuvastatin is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin). The rest is excreted by the kidneys. The plasma half-life (T1 / 2) is approximately 19 hours. The half-life does not change with an increase in the dose of the drug. The geometric mean plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase inhibitors, the cholesterol membrane carrier is involved in the process of “hepatic” uptake of rosuvastatin, which plays an important role in the hepatic elimination of rosuvastatin.
Linearity
Systemic exposure of rosuvastatin increases in proportion to dose. Pharmacokinetic parameters do not change with daily use. Special patient populations.
Age and gender
Sex and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.
Ethnic groups
Pharmacokinetic studies showed an approximately twofold increase in the median AUC (area under the concentration-time curve) and Cmax (maximum plasma concentration) of rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with Caucasians in Indians showed an increase in the median AUC and Cmax by 1.3 times. Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics among Caucasians and representatives of the Negroid race.
Renal failure
In patients with mild to moderate renal failure, the plasma concentration of rosuvastatin or N-desmethylrose-vastatin does not change significantly. In patients with severe renal failure (creatinine clearance (CC) less than 30 ml / min. ) the concentration of rosuvastatin in blood plasma is 3 times higher, and the concentration of N-desmethylrosuvastatin is 9 times higher than that of healthy volunteers. The plasma concentration of rosuvastatin in hemodialysis patients was approximately 50% higher than in healthy volunteers.
Hepatic insufficiency
Patients with various stages of liver failure did not show an increase in the half-life of rosuvastatin in patients with 7 points or lower on the Child-Pugh scale. Two patients with 8 and 9 points on the Child-Pugh scale showed an increase in half-life by at least 2 times. There is no experience with rosuvastatin in patients with more than 9 Child-Pugh scores.
Indications
- Primary Fredrickson hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet, when diet and other non-drug treatments (for example, physical body mass) .
- Family homozygous hypercholesterolemia as a supplement to diet and other lipid lowering therapy (e.g., LDL apheresis), or in cases when such therapy is not effective enough.
- Hypertriglyceridemia (type IV according to Fredrickson) as a supplement to the diet.
- Primary dysbetalipoproteinemia (type III according to Frederickson) as a supplement to the diet.
- To slow the progression of atherosclerosis as a supplement to the diet in patients who are shown therapy to reduce the concentration of total cholesterol and LDL-C.
- Primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary artery disease, but with an increased risk of developing it (over 50 years old for men and over 60 years old for women, increased concentration of C-reactive protein ( 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low concentration of HDL-C, smoking, family history of early onset of CHD).
Contraindications
For the rosuvastatin-C3 drug in a daily dose of 5 mg, 10 mg and 20 mg:
- hypersensitivity to rosuvastatin or any of the components of the
drug - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose)
- children under 18 years of age
- liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared with upper limit of norm)
- severe renal failure (CC less than 30 ml / min.)
- myopathy
- concomitant use of cyclosporine
- in women: pregnancy, breast-feeding, lack of adequate methods of contraception
- increased creatine phosphokinase (CPK) concentration in the blood by more than 5 times compared with the upper limit of
norm - combined use with
HIV protease inhibitors in patients predisposed to the development of myotoxic complications
For the daily dose of rosuvastatin-SZ 40 mg:
- hypersensitivity to rosuvastatin or any of the components of the
drug - lactose intolerance, lactase deficiency or glucose-galactose malabsorption - the drug contains 18 years old
- concomitant use of cyclosporine
- in women: pregnancy, period of breastfeeding, lack of adequate methods of contraception
- increased concentration of creatine phosphokinase (CPK) in cro vi more than 5 times compared with the upper limit of normal
- combined use with HIV protease inhibitors
- moderate and severe renal failure (CC less than 60 ml / min.)
- liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared with the upper limit of normal) for patients with risk factors for myopathy / rhabdomyolysis, namely:
- hypothyroidism
- myotoxicity while taking other inhibitors History of HMG-CoA reductase or fibrate
- excessive alcohol consumption
- conditions that can lead to an increase in plasma concentration of rosuvastatin
- concomitant use of
fibrates - myopathy
- personal or family history of muscle diseases
- for patients of the Mongoloid race
With caution
For the daily dose of Rosuvastatin-SZ 5 mg, 10 mg and 20 mg: Risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates excessive alcohol consumption over the age of 65 years, conditions in which there is an increase in the plasma concentration of rosuvastatin race (Mongoloid race) simultaneous administration with fibrates ( see the section “Pharmacokinetics”) history of liver disease sepsis arterial hypotension extensive surgery, trauma, ty elye metabolic, endocrine or electrolyte disorders, or uncontrolled seizures. Concomitant use with colchicine and with ezetimibe (see section "Interaction with other drugs"). For the drug Rosuvastatin-SZ in a daily dose of 40 mg: Renal failure of mild severity (CC more than 60 ml / min) age over 65 years of liver disease in the history of sepsis arterial hypotension extensive surgery, trauma, severe metabolic, endocrine or electrolyte disturbances or uncontrolled seizures. Concomitant use with colchicine and with ezetimibe (see section "Interaction with other drugs"). Patients with liver failure There is no data or experience with the use of the drug in patients with more than 9 Child-Pugh scores (see the sections “Pharmacodynamics” and “Special Instructions”).
Use during pregnancy and lactation
Rosuvastatin-SZ is contraindicated during pregnancy and during breastfeeding. Women of reproductive age should use adequate methods of contraception. Since cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefits of using the drug in pregnant women. In case of pregnancy during treatment, the drug should be stopped immediately. Data on the allocation of rosuvastatin with breast milk are not available, therefore, during the period of breastfeeding, the drug should be discontinued (see section "Contraindications").
Composition
Active ingredient: calcium rosuvastatin in terms of rosuvastatin - 20 mg.
Excipients: core - lactose monohydrate (milk sugar) - 67, 6 mg calcium hydrogen phosphate dihydrate - 20.0 mg povidone (polyvinylpyrrolidone medium molecular weight) - 9.0 mg croscarmellose sodium (primellose) - 6.6 mg sodium stearyl fumarate - 2.0 mg silicon colloidal dioxide (aerosil) - 0.8 mg microcrystalline cellulose - 74.0 mg coating - Opadry II (polyvinyl alcohol, partially hydrolyzed - 2.64 mg macrogol (polyethylene glycol) 3350 - 0.741 mg talc - 1.2 mg titanium dioxide E 171 - 1.1502 mg soy lecithin E 322 - 0.21 mg indigo carmine dye-based aluminum varnish - 0.0036 mg azorubi dye-based aluminum varnish - 0.0306 mg Aluminum lacquer based dye Ponceau [Ponceau 4R] - 0,0246 mg).
Dosage and administration
Inside, do not chew or grind the tablet, swallow whole, washed down with water. The drug can be prescribed at any time of the day, regardless of food intake. Before starting therapy with Rosuvastatin-S3, the patient should begin to follow a standard hypocholesterolemic diet and continue to follow it during treatment. The dose of the drug should be selected individually depending on the goals of therapy and the therapeutic response to treatment, taking into account current recommendations on target lipid concentrations. The recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 mg or 10 mg of the drug Rosuvastatin-SZ 1 time per day. When choosing an initial dose, one should be guided by the individual cholesterol content and take into account the possible risk of cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, the dose can be increased to a larger after 4 weeks (see section "Pharmacodynamics"). Due to the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug (see section “Side effects”), increasing the dose to 40 mg after an additional dose is higher than the recommended initial dose for 4 weeks therapy can be performed only in patients with severe hypercholesterolemia and with 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 who will be under the supervision of a specialist (see section "Special instructions"). Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. A dosage of 40 mg is not recommended for patients who have not previously consulted a doctor. After 2-4 weeks of therapy and / or with an increase in the dose of the drug Rosuvastatin-SZ, monitoring of lipid metabolism is necessary (dose adjustment is necessary if necessary).
Homozygous hereditary hypercholesterolemia
Recommended starting dose is 20 mg once daily.
Elderly patients
Patients over the age of 65 are advised to start using the drug with a dose of 5 mg once a day.
Patients with renal failure
Dose adjustment is not required in patients with mild or moderate renal failure.
In patients with severe renal failure (CC less than 30 ml / min.), the use of the drug Rosuvastatin-SZ is contraindicated. The use of the drug in a dose of 40 mg is contraindicated in patients with moderate impaired renal function (CC 30-60 ml / min.) (See sections "Special Instructions" and "Pharmacodynamics"). For patients with moderate impaired renal function, an initial dose of 5 mg is recommended.
Patients with liver failure
Rosuvastatin-S3 is contraindicated in patients with active liver disease (see section "Contraindications").
Special Populations.
Ethnic groups When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin among Japanese and Chinese was noted (see section "Special Instructions"). This fact should be taken into account when prescribing Rosuvastatin-SZ to these patient groups. When prescribing doses of 10 mg and 20 mg, the recommended initial dose for patients of the Mongoloid race is 5 mg. The administration of the drug in a dose of 40 mg is contraindicated for patients of the Mongoloid race (see section "Contraindications").
Patients predisposed to myopathy
Administration of the drug in a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy (see section "Contraindications"). When prescribing doses of 10 mg and 20 mg, the recommended initial dose for this group of patients is 5 mg (see section "Contraindications").
Use with concomitant therapy
With the simultaneous use of the drug with gemfibrozil, fibrates, nicotinic acid in a dose of more than 1 g / day, an initial dose of 5 mg is recommended for patients. The dose of the drug Rosuvastatin-SZ should not exceed 10 mg once a day.
Side effects
Side effects observed when taking Rosuvastatin-SZ are usually mild and go away on their own. As with other HMG-CoA reductase inhibitors, the incidence of side effects is mainly dose-dependent. The frequency of adverse effects is presented as follows: often (> 1 / 100.1 / 1000.1 / 10000, < 1/1000) is very rare (<1/10000), the frequency is unknown (according to available data, it is not possible to establish the frequency of occurrence), including individual messages.
immune system Rarely: hypersensitivity reactions, including angioedema.
Endocrine system
Often: type 2 diabetes mellitus
From the central nervous system
Often: headache, dizziness
From the digestive tract
Often: constipation, nausea, abdominal pain Rarely: pancreatitis
From the side : pruritus, rash, urticaria
From the musculoskeletal system
Often: myalgia Rarely: myopathy (including myositis), rhabdomyolysis
Other
Often: asthenic syndrome
From the urinary system
In patients receiving rosuvastatin-SZ, proteinuria can be detected. Changes in the amount of protein in the urine (from the absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10 to 20 mg of the drug, and in approximately 3% of patients receiving 40 mg of the drug. A slight change in the amount of protein in the urine was observed when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or progression of an existing kidney disease.
From the musculoskeletal system
The following effects on the musculoskeletal system: myalgia, myopathy (including myositis), have been reported with the use of the drug Rosuvastatin-SZ in all doses, and especially when taking doses of the drug in excess of 20 mg in rare cases, rhabdomyolysis with acute renal failure or without it. A dose-dependent increase in the activity of creatine phosphokinase (CPK) is observed in a small number of patients taking rosuvastatin. In most cases, it was mild, asymptomatic and temporary. In case of increased activity of CPK (more than 5 times compared with the upper limit of normal), therapy should be suspended (see section "Special instructions").
On the part of the liver
When using rosuvastatin, a dose-dependent increase in the activity of “liver” transaminases is observed in a small number of patients. In most cases, it is insignificant, asymptomatic and temporary.
Laboratory indicators
When using the drug Rosuvastatin-SZ, the following changes in laboratory parameters were also observed: an increase in glucose concentration, bilirubin, activity of gamma-glutamyl transpeptidase, alkaline phosphate, thyroid dysfunction.
Post-marketing use of
The following side effects have been reported in the post-marketing use of rosuvastatin-C3:
From the digestive tract
Very rare: jaundice, hepatitis Rarely: increased activity of hepatic transaminases. Frequency unknown: diarrhea, fatal and non-fatal liver failure
From the musculoskeletal system
Very rare: arthralgia. Frequency unknown: Immune-mediated necrotizing myopathy
Central nervous system
Very rare: polyneuropathy, forgetfulness, amnesia, memory loss, confusion Respiratory system Frequency unknown: cough, dyspnea
From the urinary system
Very rare: hematuria, microhematuria
From the skin and subcutaneous fat
Frequency unknown: Stevens-Johnson syndrome From the reproductive system and mammary gland Frequency unknown: gynecomastia
Other unknown:
thrombocytopenia is an interstitial lung disease. The following side effects have been reported with some statins: depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction.
Lekarstvennoe
Interaction Effect Application preparations for the second rosuvastatin
Ynhybytor transportn h proteins: rosuvastatin binds to some transport proteins, in particular OATP1B1 and BCRP. The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the plasma concentration of rosuvastatin and an increased risk of myopathy (see Table 1, Methods and Doses and Special Instructions).
Cyclosporine: when co-administered with rosuvastatin and cyclosporine, the AUC of rosuvastatin was, on average, 7-fold higher than that observed in healthy volunteers (see Table 1). Does not affect the plasma concentration of cyclosporine. Rosuvastatin-SZ is contraindicated in patients receiving cyclosporine (see “Contraindications”).
HIV protease inhibitors: Although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in rosuvastatin exposure (see Table 1). A pharmacokinetic study of 20 mg rosuvastatin concurrently with a combination drug containing two HIV protease inhibitors (lopinavir, 400 mg + ritonavir, 100 mg) resulted in approximately two and fivefold increases in AUC0-24 and Cmaxatin, respectively, in healthy volunteers. Therefore, concomitant administration of rosuvastatin and HIV protease inhibitors is not recommended (see “Contraindications”, “Method of administration and dose” and “Special instructions”, Table 1).
Gemfibrozil and other lipid-lowering agents: co-administration of rosuvastatin and gemfibrozil results in a 2-fold increase in the plasma Cmax of rosuvastatin in plasma and the AUC of rosuvastatin (see “Special instructions”). Based on the specific interaction data, FCV with fenofibrate is not expected, possibly PDV.
Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increased the risk of myopathy when co-administered with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy. . With the simultaneous administration of the drug with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), patients are recommended an initial dose of the drug 5 mg, a dose of 40 mg is contraindicated when co-administered with fibrates (see "Contraindications", "Method of use and doses "," Special instructions ").
Ezetimibe: concomitant use of the drug Rosuvastatin-SZ at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see table 1). An increase in the risk of side effects due to PDV between Rosuvastatin-SZ and ezetimibe cannot be ruled out.
Antacids: the simultaneous administration of rosuvastatin and suspensions of antacids containing magnesium and aluminum hydroxide results in a decrease in the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are administered 2 hours after taking rosuvastatin. The clinical significance of such interaction has not been studied.
Erythromycin: co-administration of rosuvastatin and erythromycin results in a 20% decrease in rosuvastatin AUC and a 30% decrease in rosuvastatin Cmax. Such interaction may result from increased intestinal motility caused by erythromycin intake.
Cytochrome P450 isoenzymes: results from in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these enzymes. Therefore, no interaction of rosuvastatin with other drugs is expected at the level of metabolism with the participation of cytochrome P450 isoenzymes.
No clinically relevant interaction of rosuvastatin with fluconazole (inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (CYP2A6 and CYP3A4 isoenzyme inhibitor) was noted.
Interaction with a drug that requires a dose adjustment of rosuvastatin (see Table 1)
The dose of the drug Rosuvastatin-SZ should be adjusted, if necessary, when co-administered with drugs that increase the exposure of rosuvastatin. If the exposure is expected to increase by 2 times or more, the initial dose of Rosuvastatin-SZ should be 5 mg once daily. The maximum daily dose of Rosuvastatin-NW should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for the 40 mg dose taken without the simultaneous administration of drugs interacting with rosuvastatin. For example, the maximum daily dose of Rosuvastatin-SZ when co-administered with gemfibrozil is 20 mg (increase in exposure by 1.9 times), with ritonavir / atazanavir - 10 mg (increase in exposure by 3.1 times).
Table 1
Effect of concomitant therapy on rosuvastatin exposure (AUC, data in descending order) - results of published clinical trials
Concomitant regimenRosavastatin administration reg. 7.1 times
atazanavir, 300 mg + ritonavir, 100 mg, once daily, 8 days10 mg once Increased by 3.1 times
Lopinavir, 400 mg + ritonavir, 100 mg, 2 times a day, 17 days 20 mg once a day, 7 days Increase 2.1 times
Ge fibrosil, 600 mg 2 times a day, 7 days80 mg once Increase 1.9 times
Eltrombopag, 75 mg once a day, 10 days10 mg once Increase 1.6 times
Darunavir, 600 mg + ritonavir, 100 mg, 2 times per day, 7 days 10 mg once a day, 7 days Increase 1.5 times
Tipranavir, 500 g + ritonavir, 200 mg, 2 times daily, 11 days10 mg once Increase 1.4 times
Dronedarone, 400 mg 2 times dailyNo data Increase 1.4 times
Itraconazole, 200 mg once a day, 5 days10 or 80 mg once Increase 1.4 times
Ezetimibe, 10 mg once a day, 14 days10 mg once a day, 14 days Increase 1.2 times
Fosampravir, 700 mg + ritonavir , 100 mg, 2 times a day, 8 days10 mg once Without changes
Aleglitazar, 0.3 mg, 7 days40 mg, 7 days Without changes
Silymarin, 140 mg 3 times a day, 5 days10 mg once Without changes of
Fenofibrate, 67 mg 3 times a day, 7 days 10 mg, 7 days Without changes of
Rifampin, 450 mg once a day, 7 days20 mg once Without changes of
Ketoconazole, 200 mg 2 times a day, 7 days80 mg once without changes of
Fluconazole, 200 mg once a day, 11 days80 mg once without changes
Erythromycin, 500 mg 4 times a day, 7 days80 mg once Reduction by 28%
Baikalin, 50 mg 3 times a day, 14 days20 mg Reduction by 47%
Effect of rosuvastatin on other drugs
Vitamin K antagonists: initiation of rosuvastatin therapy or increasing the drug dose in patients receiving concomitant vitamin K antagonists (eg warfarin) may lead to an increase in MHO. Withdrawing rosuvastatin or reducing the dose of the drug can lead to a decrease in MHO. In such cases, MHO monitoring is recommended.
Oral contraceptives / hormone replacement therapy: concomitant use of rosuvastatin and oral contraceptives increased the AUC of ethinyl estradiol and the AUC of norgestrel by 26 and 34%, respectively. This increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. Pharmacokinetic data on the concomitant use of the drug Rosuvastatin-SZ and hormone replacement therapy are absent, therefore, it is impossible to exclude a similar effect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.
Other drugs: no clinically relevant interaction of rosuvastatin with digoxin is expected.
Overdose
When administered with multiple daily doses, the pharmacokinetic parameters of rosuvastatin do not change. There is no specific treatment for overdose with rosuvastatin. In case of overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. Control of liver function and CPF level is required. Hemodialysis is unlikely to be effective.
Storage conditions
Store in a dry, dark place at a temperature not exceeding 30 РC.
The Expiration of
is 3 years. Do not use after the expiry date stated on the packaging.
Deystvuyuschee substances
rosuvastatin
Terms of sale from pharmacies sfl5 from
pharmacies Prescription
tablet dosage form
Formulation
Northern Star, Russia
Rosuvastatin
Release form
Tablets, film-coated, pink, round, biconvex in cross section, the core of a tablet is white or almost white vet.
Packing
10 pcs - blister packs (3) - packs of cardboard.
Pharmacological action
Pharmacotherapeutic group of the drug: lipid-lowering agent - HMG-CoA reductase inhibitor
ATX code: [C10AA07]
Pharmacological properties of
Pharmacodynamics
Mechanism of action of
Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase 3 enzyme, 3 enzyme mevalonic acid, a precursor to cholesterol. The main target of the action of rosuvastatin is the liver, where the synthesis of cholesterol (cholesterol) and the catabolism of low density lipoproteins (LDL) are carried out. Rosuvastatin increases the number of “liver” LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of very low density lipoproteins (VLDL), thereby reducing the total amount of LDL and VLDL.
Pharmacodynamics
Rosuvastatin-SZ reduces elevated concentrations of LDL cholesterol (cholesterol-LDL), total cholesterol, triglycerides (TG), increases the concentration of high-density lipoprotein cholesterol (HDL-cholesterol), and also reduces the concentration of apolipoprotein B non-HDL, cholesterol-VLDL, TG-VLDLP and increases the concentration of apolipoprotein A-I (ApoA-I), reduces the ratio of cholesterol-LDL / cholesterol-HDL, total cholesterol-cholesterol-HDL and cholesterol-HDL / cholesterol-HDL and the ratio of apoV / ApoA-I. The therapeutic effect develops within one week after the start of therapy with the drug Rosuvastatin-SZ, after 2 weeks of treatment reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with regular use of the drug. Rosuvastatin-SZ is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender or age, including patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with type IIa and IIb hypercholesterolemia according to Fredrickson (the average initial concentration of LDL-C is about 4.8 mmol / L) when taking the drug at a dose of 10 mg, the concentration of LDL-C reaches less than 3 mmol / L. In patients with heterozygous familial hypercholesterolemia, receiving Rosuvastatin-SZ at a dose of 20-80 mg, there is a positive dynamics in the lipid profile. After titration to a daily dose of 40 mg (12 weeks of therapy), a decrease in the concentration of LDL-C by 53% is noted. In 33% of patients, an LDL-C concentration of less than 3 mmol / L is achieved. In patients with homozygous familial hypercholesterolemia, taking Rosuvastatin-SZ at a dose of 20 mg and 40 mg, the average decrease in the concentration of LDL-C is 22%. In patients with hypertriglyceridemia with an initial TG concentration from 273 to 817 mg / dl, treated with Rosuvastatin-SZ at a dose of 5 mg to 40 mg once a day for 6 weeks, the concentration of TG in the blood plasma was significantly reduced. An additive effect is observed in combination with fenofibrate in relation to the content of triglycerides and with nicotinic acid in lipid lowering doses in relation to the content of HDL-C (see also the section “Special Instructions”). According to the results of clinical studies, patients with severe hypercholesterolemia and a high risk of cardiovascular disease (CVD) should be prescribed a dose of 40 mg of Rosuvastatin-SZ. The results of a clinical study (The rationale for using statins for primary prevention: an interventional study evaluating rosuvastatin) showed that rosuvastatin significantly reduced the risk of developing cardiovascular complications.
Pharmacokinetics
Absorption and distribution of
The maximum concentration of rosuvastatin in blood plasma is reached approximately 5 hours after ingestion. Absolute bioavailability is approximately 20%. Rosuvastatin is metabolized mainly by the liver, which is the main site of cholesterol synthesis and metabolism of LDL-C. The volume of distribution of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.
Metabolism
Undergoes limited metabolism (about 10%). Rosuvastatin is a non-core substrate for metabolism by enzymes of the cytochrome P450 system. The main isoenzyme involved in the metabolism of rosuvastatin is the isoenzyme CYP2C9. The isoenzymes СYР2С19, СЫРЗА4, and CYP2D6 are less involved in metabolism. The main identified metabolites of rosuvastatin are N-desmethyltrosluvuvastatin and lactone metabolites. N-desmethylrozuvastatin is approximately 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is metabolites.
Excretion of
About 90% of the dose of rosuvastatin is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin). The rest is excreted by the kidneys. The plasma half-life (T1 / 2) is approximately 19 hours. The half-life does not change with an increase in the dose of the drug. The geometric mean plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase inhibitors, the cholesterol membrane carrier is involved in the process of “hepatic” uptake of rosuvastatin, which plays an important role in the hepatic elimination of rosuvastatin.
Linearity
Systemic exposure of rosuvastatin increases in proportion to dose. Pharmacokinetic parameters do not change with daily use. Special patient populations.
Age and gender
Sex and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.
Ethnic groups
Pharmacokinetic studies showed an approximately twofold increase in the median AUC (area under the concentration-time curve) and Cmax (maximum plasma concentration) of rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with Caucasians in Indians showed an increase in the median AUC and Cmax by 1.3 times. Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics among Caucasians and representatives of the Negroid race.
Renal failure
In patients with mild to moderate renal failure, the plasma concentration of rosuvastatin or N-desmethylrose-vastatin does not change significantly. In patients with severe renal failure (creatinine clearance (CC) less than 30 ml / min. ) the concentration of rosuvastatin in blood plasma is 3 times higher, and the concentration of N-desmethylrosuvastatin is 9 times higher than that of healthy volunteers. The plasma concentration of rosuvastatin in hemodialysis patients was approximately 50% higher than in healthy volunteers.
Hepatic insufficiency
Patients with various stages of liver failure did not show an increase in the half-life of rosuvastatin in patients with 7 points or lower on the Child-Pugh scale. Two patients with 8 and 9 points on the Child-Pugh scale showed an increase in half-life by at least 2 times. There is no experience with rosuvastatin in patients with more than 9 Child-Pugh scores.
Indications
- Primary Fredrickson hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet, when diet and other non-drug treatments (for example, physical body mass) .
- Family homozygous hypercholesterolemia as a supplement to diet and other lipid lowering therapy (e.g., LDL apheresis), or in cases when such therapy is not effective enough.
- Hypertriglyceridemia (type IV according to Fredrickson) as a supplement to the diet.
- Primary dysbetalipoproteinemia (type III according to Frederickson) as a supplement to the diet.
- To slow the progression of atherosclerosis as a supplement to the diet in patients who are shown therapy to reduce the concentration of total cholesterol and LDL-C.
- Primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary artery disease, but with an increased risk of developing it (over 50 years old for men and over 60 years old for women, increased concentration of C-reactive protein ( 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low concentration of HDL-C, smoking, family history of early onset of CHD).
Contraindications
For the rosuvastatin-C3 drug in a daily dose of 5 mg, 10 mg and 20 mg:
- hypersensitivity to rosuvastatin or any of the components of the
drug - lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose)
- children under 18 years of age
- liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared with upper limit of norm)
- severe renal failure (CC less than 30 ml / min.)
- myopathy
- concomitant use of cyclosporine
- in women: pregnancy, breast-feeding, lack of adequate methods of contraception
- increased creatine phosphokinase (CPK) concentration in the blood by more than 5 times compared with the upper limit of
norm - combined use with
HIV protease inhibitors in patients predisposed to the development of myotoxic complications
For the daily dose of rosuvastatin-SZ 40 mg:
- hypersensitivity to rosuvastatin or any of the components of the
drug - lactose intolerance, lactase deficiency or glucose-galactose malabsorption - the drug contains 18 years old
- concomitant use of cyclosporine
- in women: pregnancy, period of breastfeeding, lack of adequate methods of contraception
- increased concentration of creatine phosphokinase (CPK) in cro vi more than 5 times compared with the upper limit of normal
- combined use with HIV protease inhibitors
- moderate and severe renal failure (CC less than 60 ml / min.)
- liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared with the upper limit of normal) for patients with risk factors for myopathy / rhabdomyolysis, namely:
- hypothyroidism
- myotoxicity while taking other inhibitors History of HMG-CoA reductase or fibrate
- excessive alcohol consumption
- conditions that can lead to an increase in plasma concentration of rosuvastatin
- concomitant use of
fibrates - myopathy
- personal or family history of muscle diseases
- for patients of the Mongoloid race
With caution
For the daily dose of Rosuvastatin-SZ 5 mg, 10 mg and 20 mg: Risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates excessive alcohol consumption over the age of 65 years, conditions in which there is an increase in the plasma concentration of rosuvastatin race (Mongoloid race) simultaneous administration with fibrates ( see the section “Pharmacokinetics”) history of liver disease sepsis arterial hypotension extensive surgery, trauma, ty elye metabolic, endocrine or electrolyte disorders, or uncontrolled seizures. Concomitant use with colchicine and with ezetimibe (see section "Interaction with other drugs"). For the drug Rosuvastatin-SZ in a daily dose of 40 mg: Renal failure of mild severity (CC more than 60 ml / min) age over 65 years of liver disease in the history of sepsis arterial hypotension extensive surgery, trauma, severe metabolic, endocrine or electrolyte disturbances or uncontrolled seizures. Concomitant use with colchicine and with ezetimibe (see section "Interaction with other drugs"). Patients with liver failure There is no data or experience with the use of the drug in patients with more than 9 Child-Pugh scores (see the sections “Pharmacodynamics” and “Special Instructions”).
Use during pregnancy and lactation
Rosuvastatin-SZ is contraindicated during pregnancy and during breastfeeding. Women of reproductive age should use adequate methods of contraception. Since cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefits of using the drug in pregnant women. In case of pregnancy during treatment, the drug should be stopped immediately. Data on the allocation of rosuvastatin with breast milk are not available, therefore, during the period of breastfeeding, the drug should be discontinued (see section "Contraindications").
Composition
Active ingredient: calcium rosuvastatin in terms of rosuvastatin - 20 mg.
Excipients: core - lactose monohydrate (milk sugar) - 67, 6 mg calcium hydrogen phosphate dihydrate - 20.0 mg povidone (polyvinylpyrrolidone medium molecular weight) - 9.0 mg croscarmellose sodium (primellose) - 6.6 mg sodium stearyl fumarate - 2.0 mg silicon colloidal dioxide (aerosil) - 0.8 mg microcrystalline cellulose - 74.0 mg coating - Opadry II (polyvinyl alcohol, partially hydrolyzed - 2.64 mg macrogol (polyethylene glycol) 3350 - 0.741 mg talc - 1.2 mg titanium dioxide E 171 - 1.1502 mg soy lecithin E 322 - 0.21 mg indigo carmine dye-based aluminum varnish - 0.0036 mg azorubi dye-based aluminum varnish - 0.0306 mg Aluminum lacquer based dye Ponceau [Ponceau 4R] - 0,0246 mg).
Dosage and administration
Inside, do not chew or grind the tablet, swallow whole, washed down with water. The drug can be prescribed at any time of the day, regardless of food intake. Before starting therapy with Rosuvastatin-S3, the patient should begin to follow a standard hypocholesterolemic diet and continue to follow it during treatment. The dose of the drug should be selected individually depending on the goals of therapy and the therapeutic response to treatment, taking into account current recommendations on target lipid concentrations. The recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 mg or 10 mg of the drug Rosuvastatin-SZ 1 time per day. When choosing an initial dose, one should be guided by the individual cholesterol content and take into account the possible risk of cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, the dose can be increased to a larger after 4 weeks (see section "Pharmacodynamics"). Due to the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug (see section “Side effects”), increasing the dose to 40 mg after an additional dose is higher than the recommended initial dose for 4 weeks therapy can be performed only in patients with severe hypercholesterolemia and with 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 who will be under the supervision of a specialist (see section "Special instructions"). Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. A dosage of 40 mg is not recommended for patients who have not previously consulted a doctor. After 2-4 weeks of therapy and / or with an increase in the dose of the drug Rosuvastatin-SZ, monitoring of lipid metabolism is necessary (dose adjustment is necessary if necessary).
Homozygous hereditary hypercholesterolemia
Recommended starting dose is 20 mg once daily.
Elderly patients
Patients over the age of 65 are advised to start using the drug with a dose of 5 mg once a day.
Patients with renal failure
Dose adjustment is not required in patients with mild or moderate renal failure.
In patients with severe renal failure (CC less than 30 ml / min.), the use of the drug Rosuvastatin-SZ is contraindicated. The use of the drug in a dose of 40 mg is contraindicated in patients with moderate impaired renal function (CC 30-60 ml / min.) (See sections "Special Instructions" and "Pharmacodynamics"). For patients with moderate impaired renal function, an initial dose of 5 mg is recommended.
Patients with liver failure
Rosuvastatin-S3 is contraindicated in patients with active liver disease (see section "Contraindications").
Special Populations.
Ethnic groups When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin among Japanese and Chinese was noted (see section "Special Instructions"). This fact should be taken into account when prescribing Rosuvastatin-SZ to these patient groups. When prescribing doses of 10 mg and 20 mg, the recommended initial dose for patients of the Mongoloid race is 5 mg. The administration of the drug in a dose of 40 mg is contraindicated for patients of the Mongoloid race (see section "Contraindications").
Patients predisposed to myopathy
Administration of the drug in a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy (see section "Contraindications"). When prescribing doses of 10 mg and 20 mg, the recommended initial dose for this group of patients is 5 mg (see section "Contraindications").
Use with concomitant therapy
With the simultaneous use of the drug with gemfibrozil, fibrates, nicotinic acid in a dose of more than 1 g / day, an initial dose of 5 mg is recommended for patients. The dose of the drug Rosuvastatin-SZ should not exceed 10 mg once a day.
Side effects
Side effects observed when taking Rosuvastatin-SZ are usually mild and go away on their own. As with other HMG-CoA reductase inhibitors, the incidence of side effects is mainly dose-dependent. The frequency of adverse effects is presented as follows: often (> 1 / 100.1 / 1000.1 / 10000, < 1/1000) is very rare (<1/10000), the frequency is unknown (according to available data, it is not possible to establish the frequency of occurrence), including individual messages.
immune system Rarely: hypersensitivity reactions, including angioedema.
Endocrine system
Often: type 2 diabetes mellitus
From the central nervous system
Often: headache, dizziness
From the digestive tract
Often: constipation, nausea, abdominal pain Rarely: pancreatitis
From the side : pruritus, rash, urticaria
From the musculoskeletal system
Often: myalgia Rarely: myopathy (including myositis), rhabdomyolysis
Other
Often: asthenic syndrome
From the urinary system
In patients receiving rosuvastatin-SZ, proteinuria can be detected. Changes in the amount of protein in the urine (from the absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10 to 20 mg of the drug, and in approximately 3% of patients receiving 40 mg of the drug. A slight change in the amount of protein in the urine was observed when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or progression of an existing kidney disease.
From the musculoskeletal system
The following effects on the musculoskeletal system: myalgia, myopathy (including myositis), have been reported with the use of the drug Rosuvastatin-SZ in all doses, and especially when taking doses of the drug in excess of 20 mg in rare cases, rhabdomyolysis with acute renal failure or without it. A dose-dependent increase in the activity of creatine phosphokinase (CPK) is observed in a small number of patients taking rosuvastatin. In most cases, it was mild, asymptomatic and temporary. In case of increased activity of CPK (more than 5 times compared with the upper limit of normal), therapy should be suspended (see section "Special instructions").
On the part of the liver
When using rosuvastatin, a dose-dependent increase in the activity of “liver” transaminases is observed in a small number of patients. In most cases, it is insignificant, asymptomatic and temporary.
Laboratory indicators
When using the drug Rosuvastatin-SZ, the following changes in laboratory parameters were also observed: an increase in glucose concentration, bilirubin, activity of gamma-glutamyl transpeptidase, alkaline phosphate, thyroid dysfunction.
Post-marketing use of
The following side effects have been reported in the post-marketing use of rosuvastatin-C3:
From the digestive tract
Very rare: jaundice, hepatitis Rarely: increased activity of hepatic transaminases. Frequency unknown: diarrhea, fatal and non-fatal liver failure
From the musculoskeletal system
Very rare: arthralgia. Frequency unknown: Immune-mediated necrotizing myopathy
Central nervous system
Very rare: polyneuropathy, forgetfulness, amnesia, memory loss, confusion Respiratory system Frequency unknown: cough, dyspnea
From the urinary system
Very rare: hematuria, microhematuria
From the skin and subcutaneous fat
Frequency unknown: Stevens-Johnson syndrome From the reproductive system and mammary gland Frequency unknown: gynecomastia
Other unknown:
thrombocytopenia is an interstitial lung disease. The following side effects have been reported with some statins: depression, sleep disturbances, including insomnia and nightmares, sexual dysfunction.
Lekarstvennoe
Interaction Effect Application preparations for the second rosuvastatin
Ynhybytor transportn h proteins: rosuvastatin binds to some transport proteins, in particular OATP1B1 and BCRP. The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the plasma concentration of rosuvastatin and an increased risk of myopathy (see Table 1, Methods and Doses and Special Instructions).
Cyclosporine: when co-administered with rosuvastatin and cyclosporine, the AUC of rosuvastatin was, on average, 7-fold higher than that observed in healthy volunteers (see Table 1). Does not affect the plasma concentration of cyclosporine. Rosuvastatin-SZ is contraindicated in patients receiving cyclosporine (see “Contraindications”).
HIV protease inhibitors: Although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in rosuvastatin exposure (see Table 1). A pharmacokinetic study of 20 mg rosuvastatin concurrently with a combination drug containing two HIV protease inhibitors (lopinavir, 400 mg + ritonavir, 100 mg) resulted in approximately two and fivefold increases in AUC0-24 and Cmaxatin, respectively, in healthy volunteers. Therefore, concomitant administration of rosuvastatin and HIV protease inhibitors is not recommended (see “Contraindications”, “Method of administration and dose” and “Special instructions”, Table 1).
Gemfibrozil and other lipid-lowering agents: co-administration of rosuvastatin and gemfibrozil results in a 2-fold increase in the plasma Cmax of rosuvastatin in plasma and the AUC of rosuvastatin (see “Special instructions”). Based on the specific interaction data, FCV with fenofibrate is not expected, possibly PDV.
Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increased the risk of myopathy when co-administered with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy. . With the simultaneous administration of the drug with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), patients are recommended an initial dose of the drug 5 mg, a dose of 40 mg is contraindicated when co-administered with fibrates (see "Contraindications", "Method of use and doses "," Special instructions ").
Ezetimibe: concomitant use of the drug Rosuvastatin-SZ at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see table 1). An increase in the risk of side effects due to PDV between Rosuvastatin-SZ and ezetimibe cannot be ruled out.
Antacids: the simultaneous administration of rosuvastatin and suspensions of antacids containing magnesium and aluminum hydroxide results in a decrease in the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are administered 2 hours after taking rosuvastatin. The clinical significance of such interaction has not been studied.
Erythromycin: co-administration of rosuvastatin and erythromycin results in a 20% decrease in rosuvastatin AUC and a 30% decrease in rosuvastatin Cmax. Such interaction may result from increased intestinal motility caused by erythromycin intake.
Cytochrome P450 isoenzymes: results from in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these enzymes. Therefore, no interaction of rosuvastatin with other drugs is expected at the level of metabolism with the participation of cytochrome P450 isoenzymes.
No clinically relevant interaction of rosuvastatin with fluconazole (inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (CYP2A6 and CYP3A4 isoenzyme inhibitor) was noted.
Interaction with a drug that requires a dose adjustment of rosuvastatin (see Table 1)
The dose of the drug Rosuvastatin-SZ should be adjusted, if necessary, when co-administered with drugs that increase the exposure of rosuvastatin. If the exposure is expected to increase by 2 times or more, the initial dose of Rosuvastatin-SZ should be 5 mg once daily. The maximum daily dose of Rosuvastatin-NW should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for the 40 mg dose taken without the simultaneous administration of drugs interacting with rosuvastatin. For example, the maximum daily dose of Rosuvastatin-SZ when co-administered with gemfibrozil is 20 mg (increase in exposure by 1.9 times), with ritonavir / atazanavir - 10 mg (increase in exposure by 3.1 times).
Table 1
Effect of concomitant therapy on rosuvastatin exposure (AUC, data in descending order) - results of published clinical trials
Concomitant regimenRosavastatin administration reg. 7.1 times
atazanavir, 300 mg + ritonavir, 100 mg, once daily, 8 days10 mg once Increased by 3.1 times
Lopinavir, 400 mg + ritonavir, 100 mg, 2 times a day, 17 days 20 mg once a day, 7 days Increase 2.1 times
Ge fibrosil, 600 mg 2 times a day, 7 days80 mg once Increase 1.9 times
Eltrombopag, 75 mg once a day, 10 days10 mg once Increase 1.6 times
Darunavir, 600 mg + ritonavir, 100 mg, 2 times per day, 7 days 10 mg once a day, 7 days Increase 1.5 times
Tipranavir, 500 g + ritonavir, 200 mg, 2 times daily, 11 days10 mg once Increase 1.4 times
Dronedarone, 400 mg 2 times dailyNo data Increase 1.4 times
Itraconazole, 200 mg once a day, 5 days10 or 80 mg once Increase 1.4 times
Ezetimibe, 10 mg once a day, 14 days10 mg once a day, 14 days Increase 1.2 times
Fosampravir, 700 mg + ritonavir , 100 mg, 2 times a day, 8 days10 mg once Without changes
Aleglitazar, 0.3 mg, 7 days40 mg, 7 days Without changes
Silymarin, 140 mg 3 times a day, 5 days10 mg once Without changes of
Fenofibrate, 67 mg 3 times a day, 7 days 10 mg, 7 days Without changes of
Rifampin, 450 mg once a day, 7 days20 mg once Without changes of
Ketoconazole, 200 mg 2 times a day, 7 days80 mg once without changes of
Fluconazole, 200 mg once a day, 11 days80 mg once without changes
Erythromycin, 500 mg 4 times a day, 7 days80 mg once Reduction by 28%
Baikalin, 50 mg 3 times a day, 14 days20 mg Reduction by 47%
Effect of rosuvastatin on other drugs
Vitamin K antagonists: initiation of rosuvastatin therapy or increasing the drug dose in patients receiving concomitant vitamin K antagonists (eg warfarin) may lead to an increase in MHO. Withdrawing rosuvastatin or reducing the dose of the drug can lead to a decrease in MHO. In such cases, MHO monitoring is recommended.
Oral contraceptives / hormone replacement therapy: concomitant use of rosuvastatin and oral contraceptives increased the AUC of ethinyl estradiol and the AUC of norgestrel by 26 and 34%, respectively. This increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. Pharmacokinetic data on the concomitant use of the drug Rosuvastatin-SZ and hormone replacement therapy are absent, therefore, it is impossible to exclude a similar effect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.
Other drugs: no clinically relevant interaction of rosuvastatin with digoxin is expected.
Overdose
When administered with multiple daily doses, the pharmacokinetic parameters of rosuvastatin do not change. There is no specific treatment for overdose with rosuvastatin. In case of overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. Control of liver function and CPF level is required. Hemodialysis is unlikely to be effective.
Storage conditions
Store in a dry, dark place at a temperature not exceeding 30 РC.
The Expiration of
is 3 years. Do not use after the expiry date stated on the packaging.
Deystvuyuschee substances
rosuvastatin
Terms of sale from pharmacies sfl5 from
pharmacies Prescription
tablet dosage form
Formulation
Northern Star, Russia
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