Krestor - instructions for use, reviews, analogs and formulations (5 mg, 10 mg, 20 mg and 40 mg tablets) of a statin drug for the treatment of hypercholesterolemia and lowering cholesterol levels in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Crestor. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors specialists on the use of statin Krestor in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of the Crestor in the presence of existing structural analogues. Use to treat hypercholesterolemia and lower blood cholesterol levels in adults, children, as well as in pregnancy and lactation. Composition of the preparation.

Crestor - lipid-lowering drug, selective competitive inhibitor of HMG-CoA reductase.

Crestor reduces elevated LDL-cholesterol concentration (LDL-C), total cholesterol, triglycerides (TG) and increases high-density lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (apoB) neLPVP-cholesterol, HS- VLDL, VLDL-TG, reduces the ratio of LDL-C / HDL-C, total cholesterol / HDL-cholesterol and LDL-neLPVP / HDL-C ratio and apoB / ApoA-1.

Therapeutic effect develops within one week after the beginning of Krestor therapy, after 2 weeks of treatment it 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 intake of the drug.

Crestor is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia; regardless of race, sex or age, incl. in patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia 2a and 2b according to Fredrickson types (average initial concentration of LDL-C about 4.8 mmol / L) in patients receiving the drug in a dose of 10 mg of LDL-C concentration reaches the values ​​less than 3 mmol / l.

Patients with heterozygous familial hypercholesterolemia who receive Krestor in a dose of 20-80 mg show a positive dynamics of lipid profile (a study involving 435 patients). After titration to a daily dose of 40 mg (12 weeks of therapy), the concentration of LDL-C is reduced by 53%. In 33% of patients the concentration of LDL-C is less than 3 mmol / l.

The results of the JUPITER study (Justification of the use of statins for primary prevention: an interventional study evaluating rosuvastatin) in 17802 patients showed that Rosuvastatin (an active substance of the drug Crestor) significantly reduced the risk of cardiovascular complications (252 in the placebo group compared to 142 in the group rosuvastatin) (p <0.001) with a relative risk reduction of 44%. The effectiveness of therapy, was noted in the first 6 months of the drug. A statistically significant 48% reduction in the combined test, including death from cardiovascular causes, stroke and myocardial infarction (risk ratio 0.52, 95% confidence interval 0.40-0.68, p <0.001), a 54% decrease in the incidence of fatal or non-fatal myocardial infarction (risk ratio: 0.46, 95%, confidence interval 0.30-0.70) and 48% - fatal or nonfatal stroke.Overall mortality decreased by 20% in the rosuvastatin group (risk ratio: 0.80, 95%, confidence interval 0.67-0.97, p = 0.02). The safety profile of patients taking rosuvastatin at a dose of 20 mg was generally similar to the safety profile in the placebo group.

Composition

Rosuvastatin (in the form of calcium salt) + auxiliary substances.

Pharmacokinetics

Rosuvastatin is metabolized primarily by the liver, which is the main site for the synthesis of cholesterol and the metabolism of LDL-C. Vd rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to blood plasma proteins, mainly albumin.

About 90% of the dose of rosuvastatin is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin). The rest is excreted by the kidneys. As in the case of other HMG-CoA reductase inhibitors, a membrane cholesterol transporter involved in the hepatic elimination of rosuvastatin plays an important role in the hepatic elimination of rosuvastatin.

The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily intake.

Age and gender do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.

Indications

• Primary hypercholesterolemia according to Fredrickson (type 2a, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type 2b) as a supplement to the diet, when diet and other non-pharmacological therapies (eg, exercise, weight loss) are insufficient;
• family homozygous hypercholesterolemia as a supplement to diet and other lipid-lowering therapy (eg, LDL-apheresis), or in cases where such therapy is not effective enough;
• hypertriglyceridemia (type 4 by Fredrickson) 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 its development (age over 50 for men and over 60 for women,increased concentration of C-reactive protein (more than 2 mg / L), with at least one of additional risk factors, such as hypertension, low concentration of HDL-C, smoking, family history of early onset of CHD).

Forms of release

Tablets coated with 5 mg, 10 mg, 20 mg and 40 mg.

Instructions for use and dosage

Inside, do not chew and do not grind the tablet, swallow whole, squeezed water. The drug can be administered at any time of the day, regardless of food intake. Before starting therapy with Krestor, the patient should begin to follow the standard hypocholesterolemic diet and continue to observe it during treatment. The dose of the drug should be selected individually, depending on the purpose of therapy and the therapeutic response to treatment, taking into account the current recommendations for target lipid concentrations.

The recommended initial 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 the drug Krestor 1 time per day. When choosing the initial dose, one should be guided by the 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 may be increased to greater after 4 weeks.

In connection with the possible development of side effects when taken in a dose of 40 mg, compared with lower doses of the drug, an increase in the dose of up to 40 mg after additional doses above the recommended initial dose for 4 weeks of therapy can be performed only in patients with a severe degree hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who did not achieve the desired result of therapy when taking a dose of 20 mg and which will be monitored by the sp cialist. It is recommended especially careful monitoring of patients receiving the drug in a dose of 40 mg.

It is not recommended to administer the drug at a dose of 40 mg to patients who have not previously consulted a doctor. After 2-4 weeks of therapy and / or with an increase in the dose of the drug Krestor, control of the lipid metabolism parameters is necessary (if necessary, dose correction is required).

Older patients do not need a dose adjustment.

In patients with mild or moderate renal insufficiency, dose adjustment is not required. In patients with severe renal insufficiency (CC less than 30 ml / min), the use of Krestor is contraindicated. Contraindicated use of the drug in a dose of 40 mg in patients with moderate renal dysfunction (KK 30-60 ml / min). Patients with moderate impairment of renal function are recommended an initial dose of 5 mg.

Patients with hepatic impairment: Crestor is contraindicated in patients with liver disease in the active phase.

Side effect

• hypersensitivity reactions, including angioedema;
• type 2 diabetes mellitus;
• headache;
• dizziness;
• constipation;
• diarrhea;
• nausea;
• stomach ache;
• pancreatitis;
• itching;
• rash;
• hives;
• myalgia;
• myopathy (including myositis);
• rhabdomyolysis;
• proteinuria;
• hematuria;
• asthenic syndrome;
• arthralgia;
• polyneuropathy;
• memory loss;
• cough;
• dyspnea;
• Stevens-Johnson syndrome;
• gynecomastia;
• peripheral edema.

Contraindications

For the drug Krestor in a daily dose of 5 mg, 10 mg and 20 mg:

• increased sensitivity to rosuvastatin or any of the componentspreparation;
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose);
• children and adolescents under 18;
• liver diseases in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3-fold compared with IGN);
• severe renal dysfunction (KK less than 30 ml / min);
• myopathy;
• simultaneous administration of cyclosporine;
• in women: pregnancy, lactation, lack of adequate methods of contraception;
• patients who are predisposed to the development of myotoxic complications.

For the drug Krestor in a daily dose of 40 mg:

• increased sensitivity to rosuvastatin or any of the components of the drug;
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose);
• children and adolescents under 18;
• simultaneous administration of cyclosporine;
• in women: pregnancy, lactation, lack of adequate methods of contraception;
• liver diseases in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3-fold compared with IGN);
• patients with risk factors for myopathy / rhabdomyolysis, namely: renal failure of moderate severity (CK less than 60 ml / min), hypothyroidism, personal or family history of muscle disease, myotoxicity when taking other inhibitors of HMG-CoA reductase or fibrates in anamnesis;
• excessive use of alcohol;
• conditions that may lead to an increase in the plasma concentration of rosuvastatin;
• simultaneous reception of fibrates;
• patients of the Mongoloid race.

Application in pregnancy and lactation

Crestor is contraindicated in pregnancy and lactation (breastfeeding).

Women of reproductive age should apply adequate methods of contraception.

Because cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of using the drug in pregnant women.

In case of pregnancy in the process of therapy, taking the drug should be stopped immediately.

Data on the allocation of rosuvastatin with breast milk are not available, so during breast-feeding the drug should be discontinued

Application in elderly patients

No dose adjustment is required. Care must be taken.

special instructions

Influence on the kidneys

In patients who received high doses of the drug Krestor (mainly 40 mg), tubular proteinuria was observed, which, in most cases, was transient. Such proteinuria did not indicate acute kidney disease or progression of kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor the performance of kidneys during treatment.

From the side of the musculoskeletal system

When Krestor was used in all doses, especially at doses exceeding 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy, in rare cases rhabdomyolysis.

Definition of CKF

The determination of the level of CK should not be performed after intensive physical exertion or in the presence of other possible causes of increased activity of CK, which may lead to incorrect interpretation of the results. If the baseline level of CK is significantly elevated (5 times higher than ULN), after 5-7 days, a second measurement should be made. Do not start therapy if a second test confirms the baseline CK activity (more than 5 times higher than the VLN).

Before the start of therapy

When prescribing the Krestor preparation, as with other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis, the risk-to-benefit ratio of the therapy should be considered and clinical observation performed.

During therapy

The patient should be informed of the need to report immediately to the doctor about cases of sudden onset of muscle pain, muscle weakness, or spasms, especially in combination with malaise and fever. In such patients, the activity of CK should be determined. Therapy should be discontinued if the activity of CK is significantly increased (more than 5 times as compared with IGN) or if the symptoms from the muscles are pronounced and cause daily discomfort (even if the activity of CK is 5 times less than that of VGN).

If symptoms disappear and CPK activity returns to normal, consideration should be given to re-administering the drug Crestor or other HMG-CoA reductase inhibitors in smaller doses with careful monitoring of the patient.

Routine monitoring of the activity of CKK in the absence of symptoms is inappropriate.Very rare cases of immune-mediated necrotising myopathy with clinical manifestations of a reception proximal muscle weakness and increase in serum CPK levels during treatment or discontinuation of statins, including rosuvastatin. It may be necessary to conduct additional studies of the muscular system and nervous system, serological studies, as well as therapy with immunosuppressive drugs.

There were no signs of an increase in the effect on skeletal musculature when taking Krestor and concomitant therapy. However, increasing the number of reported cases of myositis and myopathy in patients taking other inhibitors of HMG-CoA reductase inhibitor in combination with a fibric acid derivatives including gemfibrozil, cyclosporin, nicotinic acid, azole antifungal agents, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Thus, the simultaneous use of the drug Krestor and gemfibrozil is not recommended.Care should be taken to weigh the risk-to-benefit ratio when using Krestor and fibrates or lipid-lowering doses of nicotinic acid together. Contraindicated taking a drug Crestor in a dose of 40 mg together with fibrates. In 2-4 weeks after the start of treatment and / or with an increase in the dose of the drug Krestor, control of the lipid metabolism parameters is necessary (if necessary, dose correction is required).

Liver

It is recommended to carry out the determination of liver function indices before the start of therapy and 3 months after the start of therapy. Admission of the drug Krestor should stop or reduce the dose of the drug if the activity of transaminases in the blood serum: 3 times higher than VGN.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy for major diseases should be performed prior to the commencement of treatment with Krestor.

HIV protease inhibitors

It is not recommended joint use of the drug with HIV protease inhibitors.

Lactose

The drug should not be used in patients with lactase deficiency, intolerance to galactose and glucose-galactose malabsorption.

Interstitial lung disease

When certain statins were used, especially for a long time, single cases of interstitial lung disease were reported. Manifestations of the disease may be shortness of breath, unproductive cough and deterioration, general well-being (weakness, weight loss and fever). If suspicion of interstitial lung disease should be stopped by statin therapy.

Diabetes mellitus type 2

In patients with a glucose concentration of 5.6 to 6.9 mmol / L, Krestor therapy was associated with an increased risk of developing type 2 diabetes.

Impact on the ability to drive vehicles and manage mechanisms

There have been no studies to study the effect of the drug Crestor on the ability to drive a vehicle and use mechanisms. Care should be taken when driving a motor vehicle or work that requires a high concentration of attention and speed of psychomotor reactions (dizziness may occur during therapy).

Drug Interactions

Cyclosporine: with simultaneous application of rosuvastatin and cyclosporine AUC, rosuvastatin was an average of 7 times higher than that seen in healthy volunteers.Joint application leads to an increase in the concentration of rosuvastatin in plasma, blood 11 times. Does not affect the plasma concentration of cyclosporine.

Indirect anticoagulants: the onset of Crestor therapy or an increase in the dose of the drug in patients receiving concomitantly indirect anticoagulants (eg, warfarin) may lead to an increase in prothrombin time (MHO). Removing rosuvastatin or reducing the dose of the drug may result in a decrease in MHO. In such cases, monitoring of MHO is recommended.

Gemfibrozil and other lipid-lowering drugs: the combined use of rosuvastatin and gemfibrozil leads to an increase in 2 times the Cmax of rosuvastatin in blood plasma and AUC of rosuvastatin. Based on the data on the specific interaction, no pharmacokinetically significant interaction with fenofibrates is expected, possibly pharmacodynamic interaction.

Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increased the risk of myopathy when used simultaneously with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when used as monotherapy.At simultaneous reception of a preparation with gsmfibrozilom, fibratami, nicotinic acid in a dose more than 1 g a day the initial dose of a preparation of 5 mg is recommended to patients.

Ezetimibe: simultaneous use of the drug Crestor and ezetimibe was not accompanied by a change in the AUC and Cmax of both drugs.

HIV protease inhibitors: Although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in exposure to rosuvastatin.

A pharmacokinetic study on the simultaneous use of 20 mg rosuvastatin with a combined preparation containing two HIV protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers resulted in approximately a two-fold and five-fold increase in AUC0-24 and Cmax rosuvastatin, respectively. Therefore, simultaneous administration of rosuvastatin and HIV protease inhibitors in the treatment of patients with HIV infection is not recommended.

Antacids: simultaneous use of rosuvastatin and suspensions of antacids containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%.This effect is less pronounced if antacids are administered 2 hours after rosuvastatin administration. The clinical significance of this interaction has not been studied.

Erythromycin: simultaneous application of Crestor and Erythromycin leads to a decrease in AUC0-24 of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. Such interaction can arise as a result of increased intestinal motility caused by the intake of erythromycin.

Oral contraceptives / hormone replacement therapy: simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinylestradiol and AUC norgestrel by 26% and 34%, respectively. This increase in plasma concentration should be taken into account when choosing a dose of plasma concentration should be taken into account when choosing a dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of the drug Krestor and hormone replacement therapy are not available, therefore, it is impossible to exclude the same effect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medicines: no clinically significant interaction between rosuvastatin and Digoxin is expected.

Isozymes of cytochrome P450: the results of studies have shown that rosuvastatin is neither inhibitor nor inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these enzymes. There was no clinically significant interaction between rosuvastatin and Fluconazole (inhibitor of isoenzymes CYP2C9 and CYP3A4) and Ketoconazole (inhibitor of isoenzymes CYP2A6 and CYP3A4). The combined use of rosuvastatin and Itraconazole (the inhibitor of the isoenzyme CYP3A4) increases the rosuvastatin AUC by 28% (clinically insignificant). Thus, the interaction associated with cytochrome P450 metabolism is not expected.

Analogues of the drug Krestor

Structural analogs for the active substance:

• Akorta;
• Mertenil;
• Rosuvastatin;
• Rosewood;
• Rosulip;
• Roxer;
• Tevastor.

Analogues for the pharmacological group (statins):

• Akorta;
• Aktalipid;
• Anistat;
• Apexstatin;
• Atherostat;
• Atokord;
• Atomax;
• Atorvastatin;
• Atorvox;
• Atoris;
• The Vasator;
• Vazilip;
• Vero Simvastatin;
• Zocor;
• Zokor forte;
• Zorstat;
• Cardiostatin;
• Leskol;
• Leskol Fort;
• Lipobay;
• Lipon;
• Lipostat;
• Lipofford;
• Liprimar;
• Liptonorm;
• Lovacor;
• Lovastatin;
• Lovasterol;
• Mevakor;
• Medostatin;
• Mertenil;
• Ovenkor;
• Pravastatin;
• Rovacor;
• Simva Hexal;
• Simvard;
• Simvakol;
• Simvale;
• Simvastatin;
• Simvastol;
• Symvor;
• Simgal;
• Simlo;
• Sinquard;
• Torvazine;
• Torvacard;
• Tulip;
• Holvasim;
• Holletar.

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