CRESTOR 10MG PILLS

Indications

- Fredrickson primary hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet when diet and other non-drug therapies (eg; exercise, weight loss) are insufficient;

- familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (for example, LDL-apheresis), or in cases when such therapy is not sufficiently effective;

- hypertriglyceridemia (type IV according to Fredrickson) as a supplement to the diet;

- to slow the progression of atherosclerosis as a supplement to the diet in patients who have been 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 years for men and over 60 years for women, increased concentration of C-reactive protein (≥ 2 mg / l) in the presence of at least one of the additional risk factors such as hypertension, low concentration of HDL-C, smoking, family history of early onset of CHD).

Adverse effects

Side effects observed when taking the drug Crestor®, usually expressed slightly and pass independently. As with the use of other inhibitors of HMG-CoA reductase, the frequency of side effects is mainly dose-dependent.

Determination of the frequency of adverse reactions: often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10 000, <1/1000); very rarely (<1/10 000), unspecified frequency (cannot be calculated from the available data).

Immune system: rarely, hypersensitivity reactions, including angioedema.

On the part of the endocrine system: often - type 2 diabetes.

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

Gastrointestinal: often - constipation, nausea, abdominal pain; rarely - pancreatitis.

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

Musculoskeletal system: often myalgia; rarely - myopathy (including myositis), rhabdomyolysis.

Other: often - asthenic syndrome.

Urogenital: 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 noted when taking a dose of 20 mg. In most cases, proteinuria diminishes or disappears during therapy and does not mean the onset or the progression of an existing kidney disease.

From the musculoskeletal system: when using the drug Crestor® in all doses, especially when taken in doses exceeding 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy (including myositis); in rare cases, rhabdomyolysis with or without acute renal failure .

A dose-dependent increase in the activity of CPK is observed in an insignificant number of patients taking rosuvastatin. In most cases, it was minor, asymptomatic and temporary. In the case of increased activity of CPK (more than 5 times compared with VGN) therapy should be suspended.

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 values: when using the drug Crestor® The following changes in laboratory parameters were also observed: an increase in the concentration of glucose, bilirubin, activity of GGT, alkaline phosphatase, dysfunction of the thyroid gland.

Post-marketing application

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

From the hemopoietic system: unspecified frequency - thrombocytopenia.

Gastrointestinal: very rarely - jaundice, hepatitis; rarely, increased activity of hepatic transaminases; unspecified frequency - diarrhea.

From the musculoskeletal system: very rarely - arthralgia; unspecified frequency - immune-mediated necrotizing myopathy.

From the side of the central nervous system: very rarely - loss or loss of memory; unspecified frequency - peripheral neuropathy.

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

Urogenital: very rarely - hematuria.

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

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

Other: unspecified frequency - peripheral edema.

When using some statins, the following side effects have been reported: depression, sleep disorders, including insomnia and nightmares, sexual dysfunction, hyperglycemia, increased glycosylated hemoglobin concentration. It was reported on isolated cases of interstitial lung disease, especially with prolonged use of drugs (see section "Special instructions").

Contraindications

For tablets of 10 mg and 20 mg:

- hypersensitivity to rosuvastatin or any of the components of the drug;

- liver diseases in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times as compared with VGN);

- pronounced impaired renal function (CC less than 30 ml / min);

- myopathy;

- simultaneous administration of cyclosporine;

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

- to patients predisposed to the development of myotoxic complications;

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

For 40 mg tablets:

- hypersensitivity 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 times as compared with VGN);

- patients with risk factors for the development of myopathy / rhabdomyolysis, namely: moderate renal insufficiency (CC less than 60 ml / min), hypothyroidism, personal or family history of muscular diseases, mytotoxicity while taking other HMG-CoA reductase inhibitors or fibrates in anamnesis;

- excessive use of alcohol;

- conditions that can 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 product contains lactose).

WITH caution

For tablets of 10 mg and 20 mg: risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, personal or family history of hereditary muscular diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; excessive drinking; age over 65; conditions in which there is an increase in the plasma concentration of rosuvastatin; race (Asian race); co-administration with fibrates (see Pharmacokinetics section; history of liver disease; sepsis; hypotension; extensive surgical interventions, injuries; severe metabolic, endocrine or electrolyte disturbances; uncontrolled seizures.

For 40 mg tablets: low-grade renal failure (CC more than 60 ml / min); age over 65; history of liver disease; sepsis; hypotension; extensive surgery, trauma; severe metabolic, endocrine or electrolyte disorders; uncontrollable seizures.

Application in pediatric practice

The efficacy and safety of the drug in children under 18 years of age has not been established. The experience of using the drug in pediatric practice is limited to a small number of children (8 years and older) with familial homozygous hypercholesterolemia. Crestor is not currently recommended.® in children under 18 years.

Patients with liver failure. Data or experience of the drug in patients with a score above 9 on the Child-Pugh scale is absent.

Use during pregnancy and lactation

Crestor® contraindicated in pregnancy and lactation (breastfeeding).

Women of reproductive age should use adequate methods of contraception.

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

In the event of pregnancy during therapy, the drug should be discontinued immediately.

Data regarding the allocation of rosuvastatin with breast milk are not available, therefore, in the period of breastfeeding, the drug should be stopped

Application for violations of the liver

Crestor is contraindicated in patients with liver disease in the active phase.

Application for violations of kidney function

In patients with mild to moderate renal insufficiency, dose adjustment is not required.In patients with severe renal failure (CC less than 30 ml / min) use of the drug Crestor® contraindicated. Use of the drug in a dose of 40 mg is contraindicated in patients with moderately impaired renal function (CK 30-60 ml / min).

Patients with moderate renal impairment are recommended an initial dose of 5 mg.

Use in children

The efficacy and safety of the drug in children under 18 years of age has not been established. The experience of using the drug in pediatric practice is limited to a small number of children (8 years and older) with familial homozygous hypercholesterolemia. Crestor is not currently recommended.® in children under 18 years.

Use in elderly patients

No dose adjustment required. Care should be taken.

special instructions

Impact on the kidneys

In patients receiving high doses of Crestor® (mostly 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 in a dose of 40 mg, it is recommended to monitor indicators of renal function during treatment.

From the musculoskeletal system

When using the drug Crestor® in all doses, especially in doses of more than 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy, in rare cases - rhabdomyolysis.

Determination of the activity of CPK

Determination of CPK activity should not be carried out after intense physical exertion or in the presence of other possible reasons for an increase in CPK activity, which may lead to a misinterpretation of the results obtained. If the initial activity of CPK is significantly increased (5 times higher than VGN), then in 5-7 days it is necessary to re-measure. It is not necessary to start therapy if the repeated test confirms the initial activity of CPK (more than 5 times higher than VGN).

Before the start of therapy

When prescribing the drug Crestor®, as well as when prescribing other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis (see section “With caution”), it is necessary to consider the ratio of risk and possible benefit of therapy and to conduct clinical observation.

During therapy

The patient should be informed of the need to immediately report to the doctor about cases of sudden onset of muscle pain, muscle weakness or spasms, especially in combination with indisposition and fever. In such patients, the activity of CPK should be determined. Therapy should be discontinued if the activity of CPK is significantly increased (more than 5 times compared to VGN) or if the symptoms of the muscles are pronounced and cause daily discomfort (even if the activity of CPK is increased no more than 5 times compared to VGN) .

If the symptoms disappear and CPK activity returns to normal, consider reappointment with Crestor.® or other HMG-CoA reductase inhibitors in smaller doses with careful monitoring of the patient.

Routine control of CPK activity in the absence of symptoms is not appropriate.

Very rare cases of immune-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of the proximal muscles and an increase in the level of CPK in the serum during treatment or when discontinuation of statins, incl. Rosuvastatin. Additional studies of the muscular system and nervous system, serological studies, and therapy with immunosuppressive agents may be required.

No signs of increased effects on skeletal muscles when taking the drug Crestor® and concomitant therapy. However, an increase in the incidence of myositis and myopathy was reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrin acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungal agents, inhibitors HIV proteases and macrolide antibiotics. Gemfibrozil increases the risk of myopathy in combination with some inhibitors of HMG-CoA reductase. Thus, the simultaneous administration of the drug Crestor is not recommended.® and gemfibrozil. The balance of risk and potential benefit should be carefully weighed when using Crestor together.® and fibrates or lipid-lowering nicotinic acid. Crestor is contraindicated® in a dose of 40 mg together with fibrates (seesections "Drug Interactions", "Contraindications").

2-4 weeks after the start of treatment and / or with increasing doses of the drug Crestor® control of lipid metabolism indices is necessary (dose adjustment is required if necessary).

Liver

It is recommended to determine the indicators of liver function before the start of therapy and 3 months after the start of therapy. Crestor drug intake® It should stop or reduce the dose of the drug if the activity of liver transaminases in serum is 3 times higher than VGN.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the treatment of major diseases should be carried out before the start of treatment with Crestor®.

Special Populations: Ethnic Groups

In the course of pharmacokinetic studies among Chinese and Japanese patients, an increase in the systemic concentration of rosuvastatin was observed compared with indicators obtained among European patients (see the sections “Dosing regimen” and “Pharmacokinetics”).

HIV protease inhibitors

Combined use of the drug with HIV protease inhibitors is not recommended (see section “Drug Interactions”).

Lactose

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

Interstitial lung disease

When using some statins, especially for a long time, isolated cases of interstitial lung disease have been reported.Manifestations of the disease can be shortness of breath, unproductive cough and worsening, general well-being (weakness, weight loss and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

Type 2 diabetes

In patients with a glucose concentration of 5.6 to 6.9 mmol / l Crestor therapy® was associated with an increased risk of developing type 2 diabetes.

Influence on ability to drive motor transport and control mechanisms

No studies have been conducted to study the effect of Crestor.® ability to drive and use mechanisms. Caution must be exercised when driving or working that requires increased concentration and psychomotor speed (dizziness may occur during therapy).

Overdose

When several daily doses are taken simultaneously, the pharmacokinetic parameters of rosuvastatin do not change.

There is no specific treatment for an overdose of rosuvastatin. In case of overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the functions of vital organs and systems. The control of liver function and the level of CPK is necessary. It is unlikely that hemodialysis will be effective.

Drug interaction

Effect of the use of other drugs on rosuvastatin

Transport protein inhibitors: Rosuvastatin binds to certain transport proteins, in particular, OATP1B1 and BCRP. The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in plasma concentration of rosuvastatin and an increased risk of myopathy (see Table 3 and the sections "Dosing regimen" and "Special instructions").

Cyclosporine: with the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers (see table 3). It does not affect the plasma concentration of cyclosporine. Crestor® contraindicated in patients taking cyclosporine (see Contraindications section).

HIV protease inhibitors: Although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in the exposure of rosuvastatin (see Table 3). A pharmacokinetic study on the simultaneous use of 20 mg of rosuvastatin with a combination preparation containing two HIV protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir) in healthy volunteers resulted in an approximately twofold and fivefold increase in AUC0-24 and Cmax rosuvastatin respectively. Therefore, the concomitant use of rosuvastatin and HIV protease inhibitors is not recommended (see sections “Dosing regimen”, “Special instructions”, Table 3).

Gemfibrozil and other lipid-lowering drugs: the combined use of rosuvastatin and gemfibrozil leads to an increase of 2 times Cmax rosuvastatin in plasma and AUC of rosuvastatin (see section "Special instructions"). Based on data on specific interactions, pharmacokinetically significant interactions with fenofibrates are not expected, pharmacodynamic interactions are possible.

Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increased the risk of myopathy while being used with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy (see section "Special instructions") . While taking the drug with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), an initial dose of 5 mg is recommended for patients, 40 mg is contraindicated when taken together with fibrates (see "Contraindications", "Regimen dosing "," Special instructions ").

Ezetimibe: simultaneous use of the drug Crestor® at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see table 3). Increased risk of side effects due to pharmacodynamic interactions between Crestor cannot be ruled out.® and ezetimibe.

Antacids: the simultaneous use of rosuvastatin and suspensions of antacids containing Magnesium and aluminum hydroxide, reduces the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin.The clinical significance of this interaction has not been studied.

Erythromycin: simultaneous use of rosuvastatin and Erythromycin leads to a decrease in the AUC of rosuvastatin by 20% and Cmax Rosuvastatin by 30%. Such an interaction may occur as a result of increased intestinal motility caused by taking erythromycin.

Isoenzymes of cytochrome P450: In vivo and in vitro results showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, the interaction of rosuvastatin with other drugs at the metabolic level with the participation of cytochrome P450 isoenzymes is not expected. No clinically significant interaction of rosuvastatin with Fluconazole (an inhibitor of isoenzymes CYP2C9 and CYP3A4) and Ketoconazole (an inhibitor of isoenzymes CYP2A6 and CYP3A4) was noted.

Fuzidovaya acid: research on the interaction of rosuvastatin and fusidic acid was not conducted. As with other statins, post-marketing reports of cases of rhabdomyolysis with rosuvastatin and fusidic acid were received. It is necessary to closely monitor patients. If necessary, it is possible to temporarily stop taking rosuvastatin.

Drug interactions that require dose adjustment of rosuvastatin (see table 3)

Crestor Dose® should be adjusted if necessary, its joint use with drugs that increase the exposure to rosuvastatin.You should read the instructions for use of these drugs before their appointment in conjunction with the drug Crestor®. If exposure is expected to increase by 2 times or more, the initial dose of Crestor® should be 5 mg 1 time / day. You should also adjust the maximum daily dose of Crestor® so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs interacting with rosuvastatin. For example, the maximum daily dose of the drug Crestor® with simultaneous use with gemfibrozil is 20 mg (1.9 times increase in exposure), with ritonavir / atazanavir - 10 mg (3.1 times increase in exposure).

Table 3. Effect of concomitant therapy on exposure to rosuvastatin (AUC,