30 pills
Composition
Crestor 5 mg
Active substance: rosuvastatin 5 mg.
Inactive substances: lactose monohydrate, microcrystalline cellulose, calcium phosphate, magnesium stearate, crospovidone, glycerol triacetate, hypromellose, iron oxide red (E 172), titanium dioxide, purified water.
Crestor 10 mg
Active substance: rosuvastatin 10 mg.
Inactive substances: lactose monohydrate, microcrystalline cellulose, calcium phosphate, magnesium stearate, crospovidone, glycerol triacetate, hypromellose, iron oxide red (E 172), titanium dioxide, purified water.
Crestor 20 mg
Active substance: rosuvastatin 20 mg.
Inactive substances: lactose monohydrate, microcrystalline cellulose, calcium phosphate, magnesium stearate, crospovidone, glycerol triacetate, hypromellose, iron oxide red (E 172), titanium dioxide, purified water.
Pharmachologic effect
The crucifer is a lipid-lowering agent. The active substance of the drug is rosuvastatin, a competitive selective inhibitor of HMG-CoA reductase, an enzyme that transforms 3-hydroxy-3-methylglutarylcoenzyme A into a precursor of cholesterol-mevalonate. The place of application of the action of rosuvastatin is the liver, where catabolism of low-density lipoproteins (LDL) and the formation of cholesterol (CS) occurs. Rosuvastatin increases the number of hepatic receptors to low-density lipoproteins on cell membranes, which leads to increased catabolism and capture of low-density lipoproteins and inhibition of the formation of very low-density lipoproteins (VLDL). As a result, the content of low and very low density lipoproteins in serum is observed.
Rosuvastatin reduces the elevated levels of total cholesterol, triglycerides and LDL cholesterol, apolipoprotein B (ApoB), cholesterol-lowering lipoprotein cholesterol, non-HDL cholesterol, VLDL cholesterol, LDL cholesterol / HDL cholesterol, total cholesterol / HDL cholesterol, LDL cholesterol / HDL cholesterol and ApoA / I. Rosuvastatin slightly increases the content of cholesterol and ApoA-I (apolipoprotein A-I).
Maximal action of the Crestor develops after 21 days of admission and is kept constantly. After 7 days of taking the drug, the therapeutic effect of Krestor is observed, and after 14 days of use, the effectiveness of the drug is 90% of the maximum possible.
The drug is prescribed for adults with or without hypertriglyceridemia and with hypercholesterolemia, regardless of age, sex or race. The drug can be used in patients with familial hypercholesterolemia or diabetes mellitus.
Against the background of taking Crestor in a dose of 10 mg in 80% of patients with an average baseline LDL cholesterol level of 4.8 mmol / L (hypercholesterolemia IIa and in types), LDL cholesterol decreased to ≤3 mmol / l. In patients with familial hypercholesterolemia, who receive the drug in a dosage of 20-80 mg, a positive change in the lipid profile is observed (a clinical study was conducted with the participation of 435 patients).
A decrease in LDL cholesterol by 53% was observed with 12-week Crestor therapy after titration at a dose of 40 mg / day, with an LDL cholesterol ≤3 mmol / l achieved in 33% of patients. For patients with familial homozygous hypercholesterolemia, the drug was administered at a dosage of 20 and 40 mg, and against the background of Crestor treatment, the decrease in LDL-C was 22%.
When combined with fenofibrate, the additive effect (triglyceride level) was registered, which was also observed when combined with nicotinic acid (relative to HDL cholesterol).
While there is no data on the evaluation of the reduction in the number of complications that are caused by lipid profile disorders (eg, coronary heart disease) - clinical studies are currently ongoing.
The maximum concentration of the active substance in the blood plasma is observed about 5 hours after the internal application of the Crestor. Bioavailability is approximately 20%. Cumulated in the liver. Volume distribution of rosuvastatin - 134 liters. Approximately 90% of the administered dose is associated with plasma proteins (albumins).
Approximately 10% of the dose of rosuvastatin undergoes a limited metabolism. Rosuvastatin is a non-core substance for the metabolism of the cytochrome P450 system. The main enzyme that metabolizes rosuvastatin is CYP 2C9. To a lesser extent, the enzymes CYP 3A4, CYP 2C19 and CYP 2D6 are involved in the metabolism of rosuvastatin. The main metabolites of the active substance are lactone metabolites and N-dimethyl. When they were compared, it was found that N-dimethyl is about half (50%) less active than rosuvastatin. It is determined that lactone metabolites are inactive pharmacologically.
There was no increase in the parameters of the half-life of the active substance in patients with different degrees of liver failure, which were assessed on a Child-Pugh score of 7 or less. In patients evaluated at 8 and 9 on the Child-Pugh scale, the half-life was increased by at least 2 times. There is no experience with rosuvastatin in patients with hepatic insufficiency with a Child-Pugh score of 9 or more.
Application
- Therapy of atherosclerosis to slow the progression of the disease in patients who are shown to have lipid-lowering treatment;
- With homozygous familial hypercholesterolemia as an adjunct to other cholesterol lowering treatment (eg, LDL-apheresis) or diet, as well as in cases when such treatment is ineffective;
- As a supplement to the diet - with mixed hypercholesterolemia (type IIc) in the case when non-pharmacological methods (weight loss, physical activity) and nutritional changes are ineffective;
- Primary hypercholesterolemia type IIa (including family heterozygous hypercholesterolemia).
Mode of application
The drug is used inside, washed down with water, at any time of the day, regardless of food intake. Do not chew.
The dose of Crestor is selected depending on the response to the treatment and the purpose of rosuvastatin, while taking into account recommendations for target levels of lipoproteins. During treatment with the drug, the patient is prescribed a lipid-lowering diet (standard) for permanent use.
In the case of replacing the use of other HMG-CoA reductase, or with the first appointment of a Crestor, a starting dosage of 5-10 mg / day is recommended. The choice of dose depends on the individual cholesterol indicators, the risk of side effects and risk factors for future complications of the cardiovascular system. If there is insufficient effect, you can increase the dosage of Crestor not earlier than 21 days after the beginning of taking the drug (since the maximum therapeutic effect develops precisely by this time). Admission of the Crestor in a dose of 40 mg causes an increased risk of side effects of the drug compared to smaller dosages, so increasing the dose of Crestor to 40 mg / day is allowed only with a high risk of cardiovascular complications (including patients with familial hypercholesterolemia) and with severe hypercholesterolemia. Increasing the dosage to 40 mg / day is only carried out if the desired effect of using Krestor in 20 mg / day was not achieved, and the patient should be under close medical supervision. Particular attention to this patient is necessary at the first days of taking the Crestor in a dose of 40 mg / day.
Dose increase is advisable in case of insufficient desirable result when taking a dosage of 20 mg and provided that patients are under the careful supervision of a specialist. Special control is recommended at the beginning of taking 40 mg of the drug.
Patients with a geriatric profile do not need a dosage adjustment.
With renal insufficiency
Patients with mild degrees of correction of the dose is not required. Patients with insufficient renal function of moderate severity of starting dose of rosuvastatin should be 5 mg / day.
The maximum daily dosage for mild renal insufficiency is 40 mg / day, with renal insufficiency of moderate severity (with creatinine clearance level ≤60 ml / min) - 20 mg / day.
Contraindicated in the appointment of Crestor to patients with severe renal failure.
With hepatic insufficiency
The experience of using Krestor in patients with hepatic insufficiency, which is assessed by the Child-Pugh score of 9 points or more, is absent. Contraindicated the appointment of Crestor to patients with liver disease in the active phase.
Ethnic groups
There is an increase in the systemic concentration of rosuvastatin in patients of the Mongoloid race. Such patients need to start therapy with a dosage of 5 mg / day, with a maximum dose of 20 mg / day. The appointment of the Crestor for patients of the Mongoloid race at a dosage of 40 mg / day is contraindicated.
With a propensity to develop myopathy
In patients with a tendency to develop myopathy, the starting dose of rosuvastatin should be 5 mg / day, the maximum dose - 20 mg / day. Such patients are contraindicated administration of a dose of Crestor in 40 mg / day.
Side effects
The incidence of side effects, as with other HMG-CoA reductase inhibitors, depends on the dose used.
The frequency of side effects was estimated as follows: frequent side effects (≥1 / 100, ≤1 / 10), infrequent side effects (≥1 / 1000, ≤1 / 100), rare side effects (≥1 / 10,000, ≤1 / 1000), very rare side effects (≤1 / 10,000). Side effects during application of Crestor are estimated as moderately expressed and docked independently. Termination of Crestor therapy during clinical trials due to side effects was 4% or less.
From the nervous system: dizziness, headache (often).
From the side of the immune system: allergic reactions (including angioedema) are rare.
From the skin and its appendages: rashes, itching, urticaria (unintentional side effects).
From the musculoskeletal system: rhabdomyolysis and myopathy (rarely), muscle pains (often). Myopathy, muscle pain and (rarely) rhabdomyolysis were noted in patients who took any dose of Crestor, but especially those who used a dosage of 20 mg / day. The dose-related increase in the level of creatinophosphokinase (CK) observed in patients who received Krestor was in most cases not expressed, transiently and without symptoms. If the level of CK is increased 5 or more times, rosuvastatin is stopped.
From the gastrointestinal tract: constipation, abdominal pain, nausea (often), pancreatitis (rarely).
From the side of the urinary system: tubular proteinuria. There was a change in the amount of protein in the urine in gradation from absence to traces of protein or up to two pluses and more in ≤1% of patients who received a dose of Krestor 10-20 mg / day. When taking a dose of 40 mg / day, the number of such patients was approximately 3% of patients. When using the Krestor dosage of 20 mg / day, slight increases in the amount of protein in the urine were observed. Proteinuria in most cases decreased or disappeared with continued reception and was not a symptom of the development of acute kidney disease or the progression of an already existing one.
On the part of the liver: a small number of patients showed a dose-related increase in the transaminase content, as with other inhibitors of HMG-CoA reductase. The increase in transaminases in most cases was transient, without symptoms and insignificant.
Others: asthenia (often).
After widespread introduction of the Crestor into medical practice, the following side effects were also registered:
- From the musculoskeletal system: pain in the joints (rarely).
- From the nervous system: polyneuropathy (very rarely).
- From the hepatobiliary system: hepatitis and jaundice (very rarely).
Contraindications
- Liver diseases in the active stage, including a persistent increase in the level of trasaminases of unknown origin, as well as any increase in transaminases with a level 3 times or more exceeding the upper limit of the norm;
- Marked renal impairment with creatinine clearance ≤30 ml / min;
Simultaneous application of cyclosporine; - During pregnancy and breastfeeding;
- Increased sensitivity of the immune system to rosuvastatin or any other component of the crucifer;
- The drug is not prescribed to patients who do not use highly effective and effective methods of contraception;
- ·Myopathy;
- The dose of Crestor in 40 mg / day is contraindicated in patients with an increased risk of rhabdomyolysis or myopathy;
- Age to 18 years.
Pregnancy
The cruciate is contraindicated for prescribing to pregnant women. In the case of a nursing mother, breastfeeding is discontinued. Before the treatment with a Crestor in women of reproductive age, a pregnancy test should be performed. When taking the drug, you need to use adequate methods of contraception.
Drug Interactions
With simultaneous application of cyclosporine and rosuvastatin, the AUC of the latter was approximately 7 times greater than the same parameter in healthy volunteers. The simultaneous use of these drugs does not alter the plasma concentration of cyclosporine.
At the start of the treatment and during the increase in the dose of Crestor, patients who simultaneously receive warfarin and other vitamin K antagonists, as with other HMG-CoA reductase inhibitors, may experience an increase in INR-International Normalized Ratio. Canceling the Crusher or reducing its dosage causes a decrease in INR. When combining a Crestor with vitamin K antagonists, monitoring of INR (prothrombin time) is recommended.
Simultaneous use of lipid-lowering drugs (for example, hemifibrozil) and rosuvastatin causes an increase in the maximum plasma concentration of rosuvastatin and increase its AUC by a factor of 2.
The simultaneous use of ezetimibe and Krestor did not cause changes in the maximum plasma concentration of both agents, as well as AUC. Nevertheless, it is not recommended to exclude their pharmacological interaction with the development of side effects.
Pharmacokinetic interaction with fibrates is not expected, but there is a possibility of pharmacodynamics interaction. Hemofibrates, gemfibrozil, other fibrates and lipid-lowering dosages of nicotinic acid (at a dose equivalent to 1 g / day or more) potentiate the risk of myopathy with simultaneous administration with HMG-CoA reductase inhibitors. This is probably due to the fact that these agents cause the onset of myopathy when administered as monotherapy. Therefore, in this combination, it is recommended that patients first prescribe a dose of Krestor 5 mg / day.
In a pharmacokinetic test on healthy volunteers, the combination of Crestor and a combined agent containing two protease inhibitors (100 mg of ritonavor and 400 mg of lopinavir) was associated with a 2-fold increase in the AUC for the Crestor. The maximum concentration of rosuvastatin increased approximately 5-fold. Interactions with other protease inhibitors have not been studied. When Krestor is prescribed to HIV-infected patients who take ritonavir / lopinavir against the use of Krestor, the risk / benefit ratio should be taken into account, especially when the dose is increased or at the beginning of treatment.
Simultaneous reception of erythromycin and rosuvastatin causes a decrease in the AUC of rosuvastatin by 20% and a maximum plasma concentration of 30%. Similar interaction develops due to increased intestinal motility due to the administration of erythromycin.
The clinical significance of the interaction of antacids and Krestor has not been studied. Simultaneous use of antacids with the inclusion of magnesium hydroxide or aluminum and rosuvastatin causes a decrease in the concentration of the latter in blood plasma by 50%. If antacids are taken 2 hours after rosuvastatin, then this effect is less pronounced.
No clinically significant interaction with digoxin is expected.
The simultaneous use of rosuvastatin and oral contraceptives increases AUC norgestrel and AUC of ethinylestradiol by 34% and 26%, respectively. Therefore, an increase in plasma concentration should be considered when taking contraceptives. Pharmacokinetic parameters with a combination of Crestor and drugs for hormone replacement therapy have not been studied, but this interaction can not be excluded. Such a combination of drugs was widely used during clinical trials - all patients tolerated it well.
The results of the study on in vivo and in vitro interaction indicate that the active substance of Crestor is neither an inducer nor an inhibitor of the enzymes of the cytochrome P450 system. Rosuvastatin is only a weak substrate for the action of these enzymes. There was no clinically significant interaction between ketoconazole (inhibitor CYP3A4 and CYP2A6) or fluconazole (inhibitor CYP3A4 and CYP2A9) and rosuvastatin. Simultaneous reception of itraconazole (inhibitor CY P3A4) and rosuvastatin increases the AUC of the latter by 28%, which has no clinical significance. Therefore, no interaction is expected associated with the metabolism of cytochrome P450.
Overdose
When exceeding the dose of a specific treatment is not developed. Apply symptomatic and supportive therapy. When the dose is exceeded, it is necessary to control the hepatic functions and the content of creatinephosphocinase (CKF). The effectiveness of hemodialysis is unlikely.
Form of issue
Tablets of 5; 10; 20 mg. There are 28 tablets in the blister.
Storage conditions
Store at a temperature of no more than 30 ° C. Keep away from children. It is released by prescription.
Pharmacological group
Cardiovascular drugs
Antisclerotic drugs
Active ingredient: Rosuvastatin
Additionally
At an increased risk of myopathy or rhabdomyolysis, the relationship between the benefits of treatment and the potential risk must be considered; such patients are subject to close medical supervision. In the event that the level of CK increases significantly (5 times or more) even before the start of treatment, rosuvastatin should not be taken. Determination of cretin phosphokinase to control the possible development of rhabdomyolysis or myopathy is not advisable to conduct in the presence of other probable factors for an increase in CK or after intensive physical exertion, as this may contribute to an incorrect interpretation of the results obtained. In case the initial content of creatine phosphokinase is increased 5 times or more, the following determination of the enzyme in blood serum should be made no later than 5 (maximum - 7) days. You should not start Crestor treatment if the repeated determination shows a high baseline level of creatine phosphokinase (5 times greater than the upper limit of the norm).
Crestor, like other inhibitors of HMG-CoA reductase, should be administered with caution to patients with a propensity to develop myopathy / rhabdomyolysis. The risk factors for rhabdomyolysis or myopathy can be: hypothyroidism; kidney failure; conditions that cause an increase in the plasma concentration of rosuvastatin; alcohol abuse; age over 70 years; the presence of hereditary muscle diseases in a family or individual history; myotoxicity, provoked by the use of other fibrates or inhibitors of GMC-CoA reductase in history; simultaneous application of fibrates.
If Krestor is appointed to the patient, he must be informed of the obligatory immediate communication to the treating doctor about all cases of unexpected weakness in muscles, muscle aches or spasms, especially if they are accompanied by fever and malaise. Such patients require the determination of the level of creatine phosphokinase (CKF). Admission of Crestor should be discontinued if the content of CK is significantly increased (5 times or more), or when the severity of muscle symptoms, which cause constant daily discomfort, even with the content of creatine phosphokinase, not reached a 5-fold increase. If the symptoms disappear and the CPA content returns to the original physiological value, consider the possibility of re-ingesting other HMG-CoA reductase inhibitors or Crestor at doses less than the previous ones. Such a patient needs careful monitoring of the doctor. Routine control of CK in the absence of signs of rhabdomyolysis or myopathy is inappropriate.
There was no evidence of an increase in the effect of Crestor on skeletal muscle during clinical trials with concomitant therapy. Nevertheless, there are reports of an increase in the number of cases of myopathy and myositis in patients who took other HMG-CoA reductase inhibitors against the background of the use of fibrin acid derivatives (including in the administration of drugs such as nicotinic acid, gemfibrosil, cyclosporine, inhibitors proteases, azole antifungals and macrolide antibiotics). Gemfibrozil increases the risk of myopathy with a combination of Crestor with certain HMG-CoA reductase inhibitors. It is not recommended to prescribe Krestor and gemfibrozil at the same time. It is necessary to carefully evaluate the relationship between the possible benefits and potential risks in the appointment of a combination of niacin, fibrates and Crestor.
Contraindicated simultaneous appointment with fibrates of a crucifer in a dose of 40 mg.
The crucifer is not recommended for patients with acute severe conditions (eg, arterial hypotension, trauma, sepsis, extensive surgical interventions, severe endocrine, metabolic or electrolyte disturbances, as well as in the case of uncontrolled epilepsy, since these conditions may become risk factors rhabdomyolysis / myopathy).
In patients who take rosuvastatin at high doses (mostly at a dosage of 40 mg / day), cases of tubular proteinuria have been observed. Tubular proteinuria was short-lived or transitory in most cases. This proteinuria was not evidence of the development of acute kidney disease or the progression of an already existing one. Patients receiving Krestor in a dosage of 40 mg / day, it is recommended to periodically monitor the functional parameters of the kidneys during the reception of the Krestor (the entire course of therapy).
When taking rosuvastatin, especially at doses of about 20 mg / day, there were reports of effects from skeletal muscle, for example, muscle pain, rhabdomyolysis or myopathy. However, in the combination of ezetimibe and inhibitors of HMG-CoA reductase, rhabdomyolysis developed in very rare cases.
Safety and effectiveness of the use of Crestor in children are not established. In pediatric practice, the experience with the use of rosulostatin is limited to a small number of observations (children under 8 and older with homozygous familial hypercholesterolemia). Therefore, it is not recommended to use Krestor for treatment in pediatric practice.
Attention!
Description of the preparation "Krestor" on this page is a simplified and supplemented version of the official instructions for use. Before purchasing or using the drug, you should consult with your doctor and read the annotation approved by the manufacturer.
Information about the drug is provided solely for informational purposes and should not be used as a guide to self-treatment. Only the doctor can decide on the appointment of the drug, as well as determine the dose and methods of its use.