rosuvastatin | Krestor tablets are covered.pl.ob. 40 mg 28 pcs.

packaging 28 pcs

Pharmacological action

Selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol (Xc).

Rosuvastatin increases the number of hepatic LDL receptors on the cell surface, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of VLDL, thereby reducing the total amount of LDL and VLDL.

Krestor lowers high levels of LDL-C, total cholesterol, triglycerides (TG), increases HDL-C, and also lowers apolipoprotein B (ApoV), non-HDL-C, HDL-V, TG-VLDL and increases apolipoprotein 1 (ApoA-1), reduces the ratio of Xs-LDL / Xs-HDL, total Xs / Xs-HDL and Xs-non-HDL / Xs-HDL, and the ratio of ApoV / ApoA-1.

The therapeutic effect appears within 1 week. after the start of therapy and after 2 weeks of treatment is 90% of the maximum possible effect, which is usually achieved by 4 weeks and after that remains constant.

Crestor is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender or age), including in patients with diabetes mellitus and with familial hypercholesterolemia.

In 80% of patients with type IIa and type IIb hypercholesterolemia (average baseline LDL-C level of about 4.8 mmol / l) when taking the drug at a dose of 10 mg, LDL-C level reaches values. In patients with heterozygous familial hypercholesterolemia when using Crestor at a dose of 20 -80 mg showed a positive dynamics in the lipid profile (study involving 435 patients). After titration to a daily dose of 40 mg (12 weeks of therapy), there is a decrease in the level of LDL-C by 53%. In 33% of patients, the level of LDL-C is achieved in patients with homozygous familial hypercholesterolemia with the use of Krestor at a dose of 20 mg and 40 mg, the average decrease in the level of LDL-C is 22%.

The additive effect is observed in combination with fenofibrate in relation to the content of TG and with nicotinic acid in relation to the content of HDL-C.

Studies on the effect of rosuvastatin on reducing the number of complications caused by lipid disorders (such as coronary heart disease) are not yet complete.

Indications

Hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to diet, when diet and other non-drug therapies (e.g., exercise, weight loss) family homozygous hypercholesterolemia is insufficient as a supplement to diet and other cholesterol lowering therapy, or in cases where such therapy is not suitable for the patient.

Contraindications

hypersensitivity to rosuvastatin or any of the components of the

drug concomitant use of cyclosporine

in women: pregnancy, lactation, lack of adequate methods of contraception

liver disease in the active phase, including a persistent increase in serum activity of transaminase and blood (more than 3 times compared with VGN)

patients with risk factors for the development of myopathy / rhabdomyolysis, namely: renal failure with moderate severity (Cl creatinine less than 60 ml / min) hypothyroidism personal or family history of muscle diseases myotoxicity while taking other HMG-CoA reductase inhibitors or fibrates in the history of

excessive alcohol consumption

condition, which can lead to an increase in the plasma concentration of rosuvastatin

simultaneous administration of

fibrates patients of the Asian race

lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose).

Use during pregnancy and lactation

The cross is contraindicated in pregnancy and lactation. If pregnancy occurs during therapy, the drug should be stopped immediately.

Women of reproductive age should use adequate methods of contraception. Since cholesterol and its biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of using the drug.

Clinical data on the allocation of rosuvastatin with breast milk are not available, so if you need to use Krestor during lactation, breastfeeding should be stopped.

Experimental studies have found that rosuvastatin is excreted in rat milk.

Composition

1 tablet contains:

Active ingredient:

rosuvastatin (in the form of calcium salt) 40 mg

Excipients:

lactose monohydrate

MCC

calcium phosphate srdlconc magnesium phosphate.

Dosage and administration

Inside, without chewing or crushing the tablet, swallowed whole, washed down with water. The drug can be prescribed at any time of the day, regardless of food intake.

Before starting Krestor therapy, the patient should start following a standard hypocholesterolemic diet and continue following 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 concentration.

The recommended starting dose for patients starting to take the drug, or for patients transferred from other HMG-CoA reductase inhibitors, should be 5 or 10 mg of Crestor once a day. When choosing an initial dose, you should be guided by an individual concentration of cholesterol and take into account the possible risk of cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, the dose can be increased to a larger after 4 weeks.

Due to the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug, increasing the dose to 40 mg after an additional dose is higher than the recommended starting dose for 4 weeks of 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 have not achieved the desired result of therapy when taking a dose of 20 mg, and who will be under the supervision of a specialist. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

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 Krestor®, monitoring of lipid metabolism is necessary (dose adjustment is necessary if necessary).

Elderly patients. No dose adjustment required.

Patients with renal failure. In patients with mild or moderate renal failure, dose adjustment is not required. In patients with severe renal failure (Clcreatinin less than 30 ml / min), the use of the drug Krestor® is contraindicated. The use of the drug at a dose of 40 mg is contraindicated in patients with moderate impaired renal function (creatinine Cl 30-60 ml / min). For patients with moderate impaired renal function, an initial dose of 5 mg is recommended.

Patients with liver failure. Krestor® is contraindicated in patients with active liver disease.

Special populations

Ethnic groups. When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin in Japanese and Chinese was noted. This fact should be taken into account when prescribing Crestor® to these patient groups. When prescribing doses of 10 and 20 mg, the recommended initial dose for patients of the Mongoloid race is 5 mg. Administration of the drug in a dose of 40 mg is contraindicated for patients of the Mongoloid race.

Patients predisposed to myopathy. The administration of the drug at a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy. When prescribing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg.

Side effects

Immune system: rarely - hypersensitivity reactions, including angioedema.

Endocrine system: often type 2 diabetes.

From the side of the central nervous system: often - headache, dizziness.

From the digestive tract: often - constipation, nausea, abdominal pain rarely - pancreatitis.

From the skin: infrequently - itching, rash, urticaria.

From the musculoskeletal system: often - myalgia rarely - myopathy (including myositis), rhabdomyolysis.

Other: often - asthenic syndrome.

From the urinary system: in patients treated with Crestor®, 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 10–20 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: when using the drug Krestor® in all dosages and especially when taking doses of the drug exceeding 20 mg - myalgia, myopathy (including myositis) in rare cases - rhabdomyolysis with acute renal failure or without it.

A dose-dependent increase in creatine phosphokinase (CPK) activity is observed in a small number of patients taking rosuvastatin. In most cases, it was mild, asymptomatic and temporary. In the case of an increase in the level of CPK (more than 5 times compared with VGN), therapy should be suspended (see. "Special Instructions").

From the liver: with the use of rosuvastatin, a dose-dependent increase in the activity of hepatic transaminases is observed in a small number of patients. In most cases, it is insignificant, asymptomatic and temporary.

Laboratory indicators: increased glucose, bilirubin concentration, GGTP activity, alkaline phosphatase, signs of thyroid dysfunction.

Post-marketing use of

The following side effects have been reported in the post-marketing use of Crestor®.

From the digestive tract: very rarely - jaundice, hepatitis rarely - increased activity of hepatic transaminases of unspecified frequency - diarrhea.

From the musculoskeletal system: very rarely - arthralgia of unspecified frequency - immuno-mediated necrotizing myopathy.

From the side of the central nervous system: very rarely - polyneuropathy, memory loss.

From the respiratory system: unspecified frequency - cough, shortness of breath.

From the urinary system: very rarely - hematuria.

From the skin and subcutaneous fat: unspecified frequency - Stevens-Johnson syndrome.

From the reproductive system and breast: unspecified frequency - gynecomastia.

Other: unspecified frequency - peripheral edema.

Drug Interaction

Effect of other drugs on rosuvastatin

Transport protein inhibitors: rosuvastatin binds to some transport proteins, in particular, OATP1B1 and BCRP. Concomitant use of drugs, which 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 3 and sections “Dosage and administration” and “Special instructions”).

Cyclosporin: when co-administered with rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than that observed in healthy volunteers (see Table 3). Does not affect the plasma concentration of cyclosporine. Crestor® is contraindicated in patients receiving cyclosporine (see Contraindications).

Human immunodeficiency virus (HIV) protease inhibitors: Although the exact mechanism of the interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in exposure to rosuvastatin (see Table 3).

A pharmacokinetic study of concomitant administration of 20 mg rosuvastatip with a combination drug containing two HIV protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers resulted in approximately two and fivefold increases in AUC (0-24), respectively. Therefore, concomitant administration of rosuvastatin and HIV protease inhibitors is not recommended (see section “Method of administration and dose”, “Special instructions”, table 3).

Gemfibrozil and other lipid-lowering agents: co-administration of rosuvastatin and gemfibrozil results in a 2-fold increase in the maximum concentration of rosuvastatin in the blood plasma and rosuvastatin AUC (see section “Special instructions”). Based on specific interaction data, no pharmacokinetically significant interaction with fenofibrate is expected, pharmacodynamic interaction is possible.

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. ). At 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 administration and dosage "," Special instructions ").

Ezetimibe: co-administration of Crestor® 10 mg and ezetimibe 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see Table 3). An increased risk of side effects due to the pharmacodynamic interaction between Crestor® 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: concomitant administration of rosuvastatin and erythromycin results in a 20% decrease in rosuvastatin AUC and a rosuvastatin Cmax of 30%. Such interaction may result from increased intestinal motility caused by the intake of erythromycin.

Cytochrome P450 iso-fermites: results from in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 iso-enzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, interaction of rosuvastatin with other drugs at the level of metabolism with the participation of cytochrome P450 isoenzymes is not expected.

No clinically relevant interaction of rosuvastatin with fluconazole (CYP2C9 and CYP3A4 isoenzyme inhibitor) and ketoconazole (CYP2A6 and CYP3A4 isoenzyme inhibitor) was noted.

Fusidic acid: no studies have been performed to study the interaction of rosuvastatin and fusidic acid. As with other statins, Postmarketing reports of rhabdomyolysis with co-administration of rosuvastatin and fusidic acid were obtained. Patients should be closely monitored. If necessary, temporary discontinuation of rosuvastatin may be possible.

Interaction with medicinal products requiring dose adjustment of rosuvastatin (see Table 3)

The dose of Krestor® should be adjusted if necessary when co-administered with medicinal products that increase exposure to rosuvastatin. You should read the instructions for use of these drugs before their appointment together with the drug Krestor®. If the exposure is expected to increase by 2 times or more, the starting dose of Krestor® should be 5 mg once daily. You should also adjust the maximum daily dose of Krestor®, so that the expected exposure to rosuvastatin does not exceed that for the 40 mg dose taken without the concomitant administration of rosuvastatin drug. For example, the maximum daily dose of Krestor® 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 3. Effect of concomitant therapy on exposure to rosuvastatin (AUC, data in descending order) - results of published clinical trials



concomitant

therapy ., 6 months 10 mg once daily, 10 days Increase in 7, 1 time

Atazanavir 300 mg /

ritonavir 100 mg

1 time, 8 days 10 mg once Increase 3,1 times

Simeprevir 152 mg

1 time daily, 7 days 10 mg once Increase 2,8 times

lopinavir 400 mg /

ritonavir 100 mg

2 times a day, 17 days 20 mg 1 time a day, 7 days Increase 2.1 times

Clopidogrel 300 mg

(loading dose),

then 75 mg through 24 h 20 mg once Increased 2 times

Gemfibrozil 600 mg

twice daily, 7 days 80 mg once Increased 1.9 times

Eltrombopag 75 mg

once daily. 10 days 10 mg once Increase 1.6 times

Darunavir 600 mg /

ritonavir 100 mg

2 times daily, 7 days 10 mg 1 time daily, 7 days Increase 1.5 times

Tipranavir 500 mg /

ritonavir 200 mg

2 times a day, 11 days 10 mg once Increase 1.4 times

Dronedarop 400 mg

2 times a day. No data Increase 1.4 times

Itraconazole 200 mg

once daily, 5 days 10 mg or 80 mg once Increase 1.4 times

Ezetimibe 10 mg

once daily, 14 days 10 mg 1 time per day, 14 days Increase 1.2 times

Fosamprenavir 700 mg /

ritonavir 100 mg

2 times daily, 8 days 10 mg once Without changes

Aleglitazar 0.3 mg.

7 days 40 mg, 7 days No change

Silymarin 140 mg

3 times a day. 5 days 10 mg once without changes

Fenofibrate 67 mg

3 times a day, 7 days 10 mg, 7 days No changes

Rifampin 450 mg

once a day. 7 days 20 mg once without changes

Ketoconazole 200 mg

2 times a day, 7 days 80 mg once without changes

Fluconazole 200 mg

once daily, 11 days 80 mg once without changes

Erythromycin 500 mg

4 times daily, 7 days 80 mg once 28% decrease

Baikalin 50 mg

3 times a day, 14 days 20 mg once Reduced by 47%

Effect of using 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) to an increase in International Normalized tnoshenyya (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 ethinyl estradiol AUC and norgestrel AUC 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 Crestor® 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 medicines: no clinically relevant interaction of rosuvastatin with digoxin is expected.

Overdose

When co-administered with multiple daily doses, the pharmacokinetic parameters of rosuvastatin do not change.

Treatment: There is no specific antidote.

Symptomatic therapy is required if necessary, monitoring of liver function and CKF level is required. Hemodialysis is unlikely to be effective.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30 РC.

Active ingredient

Rosuvastatin

dosage form

tablets

Possible product names

Crestor tablets 40 mg, 28 pcs.

CRESTOR 0.04 N28 TABLE P / O

CRESTOR 0.04 N28 TABLE P / FILM / SHELL

CRESTOR 40MG. No. 28 TAB. P / O

CRESTOR TAB. P.P.O. 40MG No.28

AstraZeneca, Britain