Crestor( rosuvastatin)

Crestor( rosuvastatin) analogues:

Crestor( rosuvastatin) Instruction:

Manufacturer:

Active ingredients Crucible:

Form of the product:

  • Tablets coated with 10 mg No. 28( 14x2)
  • Tablets coatedSheath, 20 mg No. 28( 14x2)
  • Tablets coated with a coating, 40 mg No. 28( 7x4).

To whom is the Crestor shown?

Primary hypercholesterolemia( type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia( type IIc) as a supplement to the diet, when diet and other non-medicamentous therapies( eg exercise, weight reduction) are insufficient.

Family homozygous hypercholesterolemia as a supplement to diet and other cholesterol-lowering therapy( eg, LDL-apheresis) or in cases where such therapy is not suitable for the patient.

How to use the Crestor?

Before starting treatment, the patient should be prescribed a standard lipid-lowering diet, which he must adhere to and during treatment with a Crestor. The dose should be

selected individually, depending on the purpose of therapy and the response to treatment, guided by recommendations on target lipid levels.

The recommended initial dose for patients who begin treatment with the drug or who are transferred from taking other HMG-CoA reductase should be 5 or 10 mg per day. To select the initial dose should be guided by an individual cholesterol level and take into account the risk of cardiovascular complications in the future, as well as the risk of developing unwanted phenomena. If necessary, the dose can be increased to the next not earlier than 4 weeks later. Due to the increased risk of developing adverse events when taking 40 mg of Crestor compared to smaller doses, increasing the dose to 40 mg is possible after 4 weeks of treatment only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications( especially in patients with familial hypercholesterolemia), who did not achieve the desired result with the application of 20 mg and which will be under the close supervision of specialists. Special control is recommended at the beginning of taking 40 mg of the drug.

The cruciform is taken inside without chewing, the tablet is swallowed whole, washed down with water. The cruciate can be taken at any time, regardless of food intake.

Elderly patients

No dose adjustment is required.

Patients with renal insufficiency

Patients with renal insufficiency of mild severity do not need dose adjustment. Patients with moderate renal insufficiency should begin treatment with Krestor with a dose of 5 mg per day.

The maximum daily dose for patients with mild renal insufficiency is 40 mg, for patients with moderate renal insufficiency of 20 mg.

The use of all doses of Crestor is contraindicated in patients with severe renal failure.

A dose of 40 mg is contraindicated in patients with moderate renal insufficiency( creatinine clearance <60 ml / min.).

Patients with hepatic insufficiency

The experience of using the drug in patients with hepatic impairment with a score above 9 on the Child-Pugh scale is not available. Crestor is contraindicated in patients with liver disease in the active stage.

Ethnic groups

When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, there was an increase in its systemic concentration in patients of the Asian race. Such patients should be treated with a dose of 5 mg. A dose of 40 mg is contraindicated. The maximum daily dose is 20 mg.

Patients with a tendency to develop myopathy( see section "Contraindications")

The initial dose for these patients is 5 mg. A dose of 40 mg is contraindicated. The maximum daily dose is 20 mg.

Before starting treatment.

The crucifer, like other HMG-CoA reductase inhibitors, should be administered with caution to patients who are prone to developing myopathy / rhabdomyolysis. Risk factors can be:

  • kidney failure;
  • hypothyroidism;
  • presence of hereditary muscle diseases in an individual or family history;
  • myotoxicity caused by the taking of inhibitors of HMG-CoA reductase or fibrates in the anamnesis;
  • alcohol abuse;
  • is more than 70 years old;
  • conditions that may lead to an increase in the concentration of rosuvastatin in plasma;
  • simultaneous application of fibrates.

In such cases, the risk-benefit ratio of treatment should be considered, and these patients should be carefully monitored. If the level of CK is significantly elevated( 5 times higher than the upper limit of the norm) even before the start of therapy, rosuvastatin should not be prescribed.

During treatment, the patient should be informed of the need to report immediately to the doctor about cases of unexpected muscle pain, muscle weakness or spasms, especially if they are combined with malaise and fever. In such patients, the level of CK should be determined. Treatment should be discontinued if the level of CK is significantly increased( by 5 or more times comparing with the upper limit of the norm) or if the muscle symptoms are pronounced and cause daily discomfort( even if the CK level does not reach a 5-fold increase, comparing with the upper limitnorms).If symptoms disappear and CFC levels return to physiological levels, the possibility of re-administering Crestorau or other HMG-CoA reductase inhibitors in smaller doses should be considered. The patient should be carefully looked after. Routine control of CKK in the absence of symptoms is not appropriate. When conducting clinical trials, there was no evidence of increased influence on skeletal muscle when taking Crestor and concomitant therapy. However, an increase in myositis and myopathy was reported in patients taking other HMG-CoA reductase inhibitors concomitantly with fibrin acid derivatives, including gemfibrozil, with cyclosporine, nicotinic acid, azole antifungal agents, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy with concomitant administration with certain HMG-CoA reductase inhibitors. Therefore, it is not recommended to simultaneously appoint Krestor and gemfibrozil. Care should be taken to evaluate the risk-benefit relationship with the simultaneous administration of Crestor and fibrates or niacin.

Simultaneous application of a Crestor in a dose of 40 mg with fibrates is contraindicated.

Crestor on the trail should be prescribed to patients with severe severe conditions, such as sepsis, hypotension, extensive surgery, trauma, severe metabolic, endocrine or electrolyte disorders or uncontrolled epilepsy, which may be risk factors for myopathy / rhabdomyolysis.

Effect on the kidneys. In patients who received high doses of Crestor( mainly 40 mg), tubular proteinuria was observed, which in most cases was temporary or transient. This proteinuria was not evidence of the onset or progression of an existing kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to periodically monitor the indicators of kidney function during treatment.

Effect on skeletal musculature. In the treatment with Crestor( especially at doses> 20 mg), skeletal muscle effects such as myalgia, myopathy and rarely, rhabdomyomizia were observed.

Definition of creatine phosphokinase( CKF).The determination of CK should not be performed after intensive physical exertion or in the presence of other probable causes of increase in CK, which may lead to incorrect interpretation of the results. In case, when the initial level of CK is increased( 5 times higher than the upper limit of the norm), the repeated test should be carried out after 5 to 7 days. Do not start therapy if a second test confirms high output of CK( 5 times higher than the upper limit of normal).

Children. Efficacy and safety of use in children are not established. Experience in pediatric practice is limited to a small number of children( 8 years and older) with family homozygous hypercholesterolemia. It is not recommended to assign the Krestor to children.

Crosshead effects.

The adverse events that were observed during treatment with Crestor were moderately expressed and passed independently. The frequency of discontinuation due to adverse events in clinical trials was less than 4%.The incidence of adverse events was assessed on the following scale: often( 1/100, <1/10), infrequently( & gt; 1/1000, & lt; 1/100), rarely( & gt; 1 / 10,000, & lt; 1 /1000), very rarely( & lt; 1 / 10,000).

  • From the side of the immune system
    caustically: hypersensitivity reactions, including angioedema.
  • From the nervous system
    Often: headache, dizziness.
  • From the gastrointestinal tract
    Often: constipation, nausea, abdominal pain.
  • From the skin and appendages
    infrequently: itching, rash and hives.
  • From the musculoskeletal system
    • Often: myalgia.
    • Rarely: myopathy and rhabdomyolysis.
  • Common violations of
    Often: asthenia.
  • As with other inhibitors of HMG-CoA reductase, the incidence of adverse events is dose-dependent.

  • From the side of the urinary system: in patients taking Krestor, there may be proteinuria, mostly tubular. A change in the amount of protein in the urine( from absence to traces or up to + + and more) was observed in & lt;1% of patients who received 10 to 20 mg of the drug, and approximately 3% received 40 mg. Minor changes in the amount of protein in the urine were observed with the intake of 20 mg. In most cases, proteinuria decreased or disappeared with continued therapy and is not a sign of the onset or progression of an existing kidney disease.
  • From the skeletal musculature: myalgia, myopathy and rarely rhabdomyolysis have been observed in patients who took all doses and especially those who took the drug at a dose of more than 20 mg.
  • A dose-related increase in creatine phosphokinase( CK) was observed in patients taking rosuvastatin, and in most cases it was insignificant, asymptomatic and temporary. When the level of CK is increased( by 5 or more times compared with the upper limit of the norm), therapy with rosuvastatin should be suspended.
  • From the liver side: as with the administration of other inhibitors of HMG-CoA reductase, a dose-dependent increase in transaminase activity in a small number of patients was observed. In most cases, it was insignificant, asymptomatic and temporary.

In addition to the above, following the introduction of the drug into broad medical practice, the following phenomena have been observed:

  • From the hepato-biliary system:
    • Rarely is an increase in the activity of transaminases.
    • Very rarely - jaundice, hepatitis.
  • From musculoskeletal system:
    Rarely - arthralgia.
  • From the nervous system:
    Very rarely - polyneuropathy.

Who is contraindicated with the Crestor?

  • Hypersensitivity to rosuvastatin or any component of the tablet;
  • liver disease in the active phase, including a persistent increase in transaminase activity that can not be explained, and any increase in transaminase activity by 3 or more times, comparing with the upper limit of the norm;
  • marked renal impairment( creatinine clearance & lt; 30 mL / min);
  • myopathy;
  • simultaneous application of cyclosporine;
  • pregnancy and lactation;
  • is not prescribed for women who do not use adequate contraception;
  • age to 18 years.

A dose of 40 mg is contraindicated in patients who have an increased risk of developing myopathy / rhabdomyolysis. Such factors are:

  • moderate renal failure( creatinine clearance & lt; 60 mL / min);
  • hypothyroidism;
  • presence of hereditary muscle diseases in an individual or family history;
  • myotoxicity caused by other inhibitors of HMG-CoA reductase or fibrates in the history;
  • alcohol abuse;
  • conditions that can lead to an increase in the concentration of rosuvastatin in plasma;
  • belonging to the Asian race;
  • simultaneous application of fibrates.

Interaction of the Crestor.

Cyclosporin: with simultaneous application of rosuvastatin and cyclosporin, the area under the concentration-time curve( AUC) of rosuvastatin was an average of 7 times higher, compared to that obtained in healthy volunteers. Simultaneous application does not affect the concentration of cyclosporine in the plasma.

Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, an increase in prothrombin time( INR-International Normalized Ratio) may occur at the start of therapy and with an increase in the dose of the drug in patients receiving both vitamin K antagonists( eg, warfarin).Removing the drug or reducing the dose may lead to a decrease in INR, in which case it is recommended to monitor INR.

Gemfibrozil and other lipid lowering agents: simultaneous application of rosuvastatin and hemifibrosil leads to an increaseThe maximum concentration of rosuvastatin in plasma( Cmax) and AUC of rosuvastatin is doubled, but no pharmacokinetic interaction with fibrates is expected, but there is a possibility of pharmacodynamic interaction. Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid( doses greater or more than 1 g / day) increased the risk ofmyopathies with simultaneous application with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause the development of myopathy and when used as monotherapy. Such patients are recommended to start therapy with a dose of 5 mg per day.

Antacids: simultaneous application of rosuvastatin and antacids containing aluminum or magnesium hydroxide leads to a decrease in plasma concentration of rosuvastatin by 50%.This effect is less pronounced if antacids are taken 2 hours after taking rosuvastatitis. The clinical significance of this interaction has not been studied.

Erythromycin: concomitant administration of rosuvastatin and erythromycin leads to a 20% decrease in rosuvastatin AUC and a 30% decrease in rosvastatin Cmax. Such interaction may arise due to increased intestinal motility as a result of the administration 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 considered when administering a dose of contraceptives. Pharmacokinetic data on the simultaneous use of Crestor and hormone replacement therapy are not available, so this interaction can not be ruled out. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medications: Clinically significant interaction with digoxin is not expected.

Cytochrome P450 enzymes: In vitro and in vivo studies have shown that rosuvastatin is neither inhibitor nor inducer of cytochrome P450 enzymes. In addition, rosuvastatin is a weak substrate for these enzymes. There was no clinically significant interaction between rosuvastatin and fluconazole( inhibitor CYP 2C9 and CYP 3A4) or ketoconazole( inhibitor of CYP 2A6 and CYP 3A4).Simultaneous administration of rosuvastatin and itraconazole( CYP 3A4 inhibitor) increases rosuvastatin AUC by 28%( has no clinical significance).Thus, the interaction associated with the metabolism of cytochrome P450 is not expected.

Overdose of the Crestor.

There is no specific overdose treatment. Treatment is symptomatic, supportive therapy is recommended. It is necessary to monitor liver function and the levels of CK.It is unlikely that hemodialysis will be effective.