Crestor 40 mg tablets № 28

Crestor instructions for use

pharmachologic effect

A selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutarylcoenzyme A into mevalonate, the 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 VLDL synthesis, thereby reducing the total amount of LDL and VLDL.

The crucifer reduces the high content of LDL-C, total Xc, triglycerides (TG), increases the level of X-HDL, and also reduces the content of apolipoprotein B (ApoV), Xc-non-HDL, Xc-VLDL, TG-VLDL and increases the level of apolipoprotein A-1 (ApoA-1), reduces the ratio of Xc-LDL / Xc-HDL, total Xc / Xc-HDL and Xc-non-HDL / Xc-HDL and the ApoB / ApoA-1 ratio.
The therapeutic effect is manifested within 1 week. after the start of therapy and after 2 weeks of treatment it 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, sex or age), including. in patients with diabetes mellitus and with familial hypercholesterolemia.
In 80% of patients with hypercholesterolemia IIa and IIb type (mean baseline level of LDL-C is about 4.8 mmol / L), when taking the drug at a dose of 10 mg, the level of Xc-LDL reaches values in patients with heterozygous familial hypercholesterolemia when using Krestor in a dose of 20- 80 mg positive dynamics of the lipid profile was noted (a study involving 435 patients). After titration to a daily dose of 40 mg (12 weeks of therapy), a decrease in the level of LDL-C is observed at 53%. In 33% of patients, the level of Xc-LNPP of patients with homozygous familial hypercholesterolemia is reached when using Krestor in a dose of 20 mg and 40 mg, the average decrease in the level of LDL-C is 22%.

The additive effect is noted in combination with fenofibrate for TG and nicotinic acid content for HDL-C content.
Studies on the effect of rosuvastatin on reducing the number of complications caused by lipid disorders (such as IHD) have not yet been completed.

Indications

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

Contraindications

• increased sensitivity to rosuvastatin or any of the components of the drug;
• 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 (Cl creatinine less than 60 ml / min); hypothyroidism; personal or family anamnesis of muscular diseases;
• myotoxicity on the background of 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 Asian race;
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose).

Application in pregnancy and lactation

Crestor is contraindicated in pregnancy and lactation. If pregnancy occurs during the therapy, the drug should be discontinued immediately.

Women of reproductive age should apply adequate methods of contraception. Since Xc and the products of its biosynthesis 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 the Crestor during lactation, breastfeeding should be discontinued.

In experimental studies, it has been established that rosuvastatin is excreted in rats milk.

special instructions

With caution use Krestor in the presence of risk factors for rhabdomyolysis (including renal failure, hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity when using other inhibitors of HMG-CoA reductase or fibrates), with chronic alcoholism, patients older than 70 years old, with liver diseases in history, sepsis, arterial hypotension, with extensive surgical interventions, trauma, severe metabolic endocrine or electrolyte disturbances, with uncontrolled epilepsy.

Before starting Crestor therapy, the patient should begin to follow the standard lipid-lowering diet and continue to observe it throughout the treatment period. The dose of the drug is selected individually, depending on the purpose of therapy and the response to treatment, taking into account generally accepted recommendations.
When using Krestor in a dose of 40 mg, it is recommended to monitor the parameters of kidney function.

Patients with risk factors for rhabdomyolysis should consider the risk-to-benefit ratio and conduct clinical follow-up.

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 level of CK should be determined. Therapy should be discontinued if the level of CK is significantly increased (more than 5 times compared with ULN) or if the muscle symptoms are pronounced and cause daily discomfort (even if the level of CK is 5 times lower compared to VGN). If symptoms disappear and CPK returns to normal, consideration should be given to re-administering Crestor or other HMG-CoA reductase inhibitors in smaller doses with careful monitoring of the patient.

The determination of CK should not be performed after intensive physical exertion or in the presence of other possible causes of an increase in 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 repeat test confirms the baseline level of CK (5 times higher than ULN).
Routine monitoring of CKK in the absence of symptoms is inappropriate.
There were no signs of an increase in the toxic effect on skeletal musculature when using Krestor as part of a combination therapy. An increase in the incidence of myositis and myopathy in patients taking other HMG-CoA reductase inhibitors in combination with fibrin acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid, azole antifungal agents, protease inhibitors and macrolide antibiotics has been reported. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Thus, the simultaneous administration of Crestor and gemfibrozil is not recommended. The balance of risk and possible benefit should be carefully weighed in the joint application of Crestor and fibrates or niacin.

It is recommended to perform the determination of liver function indices before the start of therapy and 3 months after the initiation of therapy. Admission of the Crestor should stop or reduce the dose of the drug, if the level of activity of transaminases in the serum is 3 times higher than VGN. In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy for major illnesses should be performed before the treatment with Crestor.

Impact on the ability to drive vehicles and manage mechanisms

When dealing with potentially hazardous activities, patients should be aware that dizziness may occur during therapy.

Composition

1 tablet contains:

Active substance: rosuvastatin (in the form of calcium salt) 40 mg;
Excipients: lactose monohydrate; ICC; calcium phosphate; crospovidone; magnesium stearate.

Dosing and Administration

Inside, without chewing and not crushing the tablet, swallowing whole, washing down with 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 on the target concentration of lipids.

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 should be guided by individual cholesterol concentration and take into account the possible risk of cardiovascular complications, as well as 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 taking a dose of 40 mg, compared with lower doses of the drug, increasing the dose to 40 mg, after additional doses above the recommended initial dose for 4 weeks of therapy, can only be carried out 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 which will be monitored by a specialist hundred. It is recommended especially careful monitoring of patients receiving the drug in a dose of 40 mg.

Do not administer 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®, it is necessary to monitor the lipid metabolism (if necessary, dose adjustment is required).

Elderly patients. No dose adjustment is required.

Patients with renal insufficiency. In patients with renal disease

insufficiency of mild or moderate severity, dose adjustment is not required. In patients with severe renal failure (less than 30 ml / min Clcrreatinin), the use of Crestor® is contraindicated. Contraindicated use of the drug in a dose of 40 mg in patients with moderate impaired renal function (Cl creatinine 30-60 ml / min). Patients with moderate impairment of renal function are recommended an initial dose of 5 mg.

Patients with hepatic insufficiency. Crestor® 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, there was an increase in the systemic concentration of rosuvastatin in Japanese and Chinese. This fact should be taken into account when prescribing Crestor® to these groups of patients. When appointing doses of 10 and 20 mg, the recommended initial dose for patients of the Mongoloid race is 5 mg. Contraindicated the appointment of the drug in a dose of 40 mg to patients of the Mongoloid race.

Patients who are predisposed to myopathy. Contraindicated the appointment of the drug in a dose of 40 mg to patients with factors that may indicate a predisposition to the development of myopathy. When appointing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg.

Side effects

Immune system: rarely - reactions of hypersensitivity, including angioedema.

Endocrine system: often - type 2 diabetes mellitus.

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 : rarely - skin itching, rash, urticaria.

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

Other : often - asthenic syndrome.

From the side of the urinary system: in patients receiving Crestor®, proteinuria can be detected. Changes in the amount of protein in the urine (from absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10-20 mg of the drug and approximately 3% of patients receiving 40 mg of the drug. A slight change in the amount of protein in the urine was noted with a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not indicate the onset or progression of an existing kidney disease.

On the part of the musculoskeletal system: with the use of the preparation Krestor® in all dosages and in particular when taking doses of the drug exceeding 20 mg - myalgia, myopathy (including myositis); in rare cases - rhabdomyolysis with or without acute renal failure.
A dose-related increase in activity of creatine phosphokinase (CK) is observed in a small number of patients taking rosuvastatin. In most cases, it was insignificant, asymptomatic and temporary. In the case of an increase in the level of CK (more than 5 times compared with VGN) therapy should be suspended (see "Special instructions").

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

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

Postmarketing application

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

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

From the side of the musculoskeletal system: very rarely - arthralgia; 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 side of the urinary system: very rarely - hematuria.

On the part of the skin and subcutaneous fat: the frequency, unspecified - Stevens-Johnson syndrome.

On the part of the reproductive system and breast : the unspecified frequency - gynecomastia.

Other: unspecified frequency - peripheral edema.

Drug Interactions

With simultaneous application of rosuvastatin and cyclosporin AUC, rosuvastatin was on average 7 times higher than the value observed in healthy volunteers, the plasma concentration of cyclosporine did not change.

The initiation of rosuvastatin therapy or an increase in the dose of the drug in patients receiving both vitamin K antagonists (eg, warfarin) may lead to an increase in the prothrombin time of the International Normalized Relationship (INR), and the withdrawal of rosuvastatin or a reduced dose of the drug may result in a decrease in INR (in such cases monitoring of INR is recommended).

The combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax in the blood plasma and AUC of rosuvastatin.

The simultaneous use of rosuvastatin and 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.

Simultaneous use of rosuvastatin and erythromycin leads to a 20% decrease in AUC of rosuvastatin and 20% in rosuvastatin Cmax and probably 30% in increased rostovastatin (probably as a result of increased intestinal motility caused by erythromycin).
The simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinylestradiol and AUC norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when choosing a dose of oral contraceptives against the background of the use of Crestor (a similar combination was widely used during clinical trials and well tolerated by patients). Pharmacokinetic data on the simultaneous application of the Crestor and hormone replacement therapy are absent, therefore, it is impossible to exclude a similar effect when using this combination.

No clinically significant interaction between rosuvastatin and digoxin or fenofibrate is expected.Gemfibrozil and other fibrates and lipid lowering doses of nicotinic acid (> = 1 g / day) increased risk of myopathy with simultaneous use with other inhibitors of HMG-CoA reductase. possibly due to the fact that they can cause myopathy and when used as monotherapy.

The results of studies in vivo and in vitro have shown that rosuvastatin is neither an inhibitor or inducer of P450 isoenzyme cytochrome. In addition, rosuvastatin is a poor substrate for these enzymes. There were no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4), and ketoconazole (an inhibitor of CYP2A6 CYP3A4). The combined use of rosuvastatin and itraconazole (CYP3A4 inhibitor) rosuvastatin AUC increases by 28% (clinically insignificant). Thus it is not expected interaction associated with the cytochrome P450 system.

Storage conditions

The drug should be kept out of reach of children at a temperature not higher than 30 ° C.

Conditions of leave from pharmacies

Available on medical prescription

Form of issue

Pills

Packaging

28 pcs.