Crestor, 5 mg 28 pcs.

Indications

Crestor is indicated for use in adults over 18 years of age:

For primary Fredrickson hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other non-drug treatments (eg, exercise, weight loss) are insufficient.
For familial homozygous hypercholesterolemia, as an adjunct to diet and other lipid-lowering therapy (eg, low-density lipoprotein (LDL) apheresis), or in cases where such therapy is not sufficiently effective.
For hypertriglyceridemia (Fredrickson type IV) as an addition to the diet.
To slow the progression of atherosclerosis as an adjunct to diet in patients who are indicated for therapy to reduce the concentration of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C).
For the primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), 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 arterial hypertension, low concentration of high-density lipoprotein cholesterol (HDL-C), smoking, family history of early onset IHD).

Pharmacological effect

Pharmacotherapeutic group: lipid-lowering agents; HMG-CoA reductase inhibitors.

Special instructions

Impact on the ability to drive vehicles and operate machinery
No studies have been conducted to study the effect of Crestor on the ability to drive a vehicle and use machinery. Caution should be exercised when driving vehicles or doing work that requires increased concentration and speed of psychomotor reactions (dizziness may occur during therapy).

Active ingredient

Rosuvastatin

Composition

Active ingredient: rosuvastatin.

Each film-coated tablet contains rosuvastatin calcium 5.20 mg (in terms of rosuvastatin 5.00 mg).
Excipients, the presence of which must be taken into account in the composition of the medicinal product: lactose monohydrate 94.88 mg.

Full list of excipients:
Lactose monohydrate
Microcrystalline cellulose (type: RN-200) Calcium phosphate
Crospovidone Magnesium stearate Tablet coating:
Lactose monohydrate Hypromellose (E464)
Triacetin (glycerol triacetate) Titanium dioxide (E171)
Iron oxide dye yellow (E172)

Pregnancy

Pregnancy
The drug Crestor is contraindicated during pregnancy and breastfeeding. Women of reproductive age should use adequate methods of contraception.
Since cholesterol and other products of cholesterol biosynthesis are important for fetal development, the potential risk of inhibiting HMG-CoA reductase outweighs the benefit of using the drug in pregnant women.
If pregnancy occurs during therapy, the drug should be discontinued immediately.

Lactation
There are no data regarding the excretion of rosuvastatin in breast milk, so the drug should be discontinued during breastfeeding.

Fertility
There are no data on the effect of rosuvastatin on reproductive function

Contraindications

hypersensitivity to rosuvastatin or any of the components of the drug;
liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times the upper limit of normal);
severe renal dysfunction (creatinine clearance less than 30 ml/min.);
myopathy;
patients predisposed to the development of myotoxic complications;
simultaneous use of cyclosporine;
in women: pregnancy, breastfeeding, lack of adequate methods of contraception;
children under 18 years of age.

A daily dose of 40 mg is contraindicated in patients with risk factors for the development of myopathy/rhabdomyolysis:

moderate renal dysfunction (creatinine clearance less than 60 ml/min.);
hypothyroidism;
personal or family history of muscle diseases;
myotoxicity due to a history of taking other hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase) inhibitors or fibrates;
excessive alcohol consumption;
conditions that can lead to increased plasma concentrations of rosuvastatin;
simultaneous use of fibrates;
patients of the Mongoloid race.

Special instructions and precautions for use

With caution

There is a risk of developing myopathy/rhabdomyolysis – impaired renal function, hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; age over 65 years; conditions in which an increase in plasma concentration of rosuvastatin is noted; race (Mongoloid race); simultaneous administration with fibrates (see section 5.2); history of liver disease; sepsis; arterial hypotension; major surgery, trauma, severe metabolic, endocrine or electrolyte disturbances, or uncontrolled seizures.

When taken in a daily dose of 40 mg:

Mild renal dysfunction (creatinine clearance more than 60 ml/min.).

Patients with liver dysfunction

There are no data or experience with the use of the drug in patients with more than 9 points on the Child-Pugh scale.

Renal effects

In patients receiving higher doses of Crestor (mainly 40 mg), tubular proteinuria was observed, which in most cases was transient.

This 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 renal function parameters during treatment.

Skeletal muscle disorders

The following effects on skeletal muscle have been reported with Crestor at all doses, and particularly at doses greater than 20 mg: myalgia, myopathy, and in rare cases, rhabdomyolysis.

Determination of creatine phosphokinase (CPK) activity

Determination of CPK activity should not be carried out after intense physical activity or in the presence of other possible reasons for increased CPK activity, which may lead to incorrect interpretation of the results obtained. If the initial CK activity is significantly increased (more than 5 times the upper limit of normal), a repeat measurement should be taken after 5-7 days. Therapy should not be started if a repeat test confirms initial CPK activity (more than 5 times the upper limit of normal).

Before starting therapy

When prescribing Crestor, as well as when prescribing other HMG-CoA reductase inhibitors, patients with existing risk factors for myopathy/rhabdomyolysis should exercise caution, it is necessary to consider the balance of risk and possible benefit of therapy and conduct clinical monitoring.

During therapy

The patient should be informed to immediately report to the doctor the unexpected onset of muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CPK activity is significantly elevated (more than 5 times the upper limit of normal), or if muscle symptoms are severe and cause daily discomfort (even if CPK activity is increased no more than 5 times the upper limit of normal). If symptoms disappear and CPK activity returns to normal, re-prescribing Crestor or other HMG-CoA reductase inhibitors in lower doses should be considered with careful monitoring of the patient.

Routine monitoring of CPK activity in the absence of symptoms is impractical. Very rare cases of immune-mediated necrotizing myopathy have been reported with clinical manifestations of persistent proximal muscle weakness and increased serum CPK activity during treatment or upon discontinuation of statins, including rosuvastatin. Additional studies of the muscular and nervous system, serological studies, and therapy with immunosuppressive drugs may be required.

There were no signs of increased effects on skeletal muscles when taking Crestor and concomitant therapy. However, an increased incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives, including gemfibrozil, cyclosporine, niacin at lipid-lowering doses (≥ 1 g/day), azole antifungals, HIV protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when used together with certain HMG-CoA reductase inhibitors. Therefore, concomitant use of Crestor and gemfibrozil is not recommended. The risk/benefit ratio should be carefully weighed when using Crestor and fibrates or nicotinic acid in lipid-lowering doses together. Taking Crestor at a dose of 40 mg together with fibrates is contraindicated.

2-4 weeks after the start of treatment and/or when increasing the dose of Crestor, monitoring of lipid metabolism is necessary (if necessary, dose adjustment is required).

Liver function

It is recommended to determine liver function indicators before starting therapy and 3 months after starting therapy. Taking Crestor should be discontinued or the dose reduced if the activity of hepatic transaminases in the blood serum is more than 3 times the upper limit of normal.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of underlying diseases should be carried out before starting treatment with Crestor.

Special populations. Ethnic groups

During pharmacokinetic studies in patients of the Mongoloid race, an increase in the systemic concentration of rosuvastatin was noted compared with the values ​​​​obtained among Caucasian patients.

HIV protease inhibitors

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

Excipients

The drug contains lactose monohydrate. Patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this drug.

Interstitial lung disease

Extremely rare cases of interstitial lung disease have been reported with some statins, especially over long periods of time. Manifestations of the disease may include shortness of breath, nonproductive cough and deterioration in general health (weakness, weight loss and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

Diabetes mellitus type 2

In patients with glucose concentrations between 5.6 and 6.9 mmol/L, treatment with Crestor was associated with an increased risk of developing type 2 diabetes.

Side Effects

Security Profile Summary

Adverse reactions reported while taking Crestor are usually mild and go away on their own. In controlled clinical trials, less than 4% of patients receiving Crestor discontinued the study early due to adverse reactions.

Tabular summary of adverse reactions

Table 2 presents a list of adverse reactions when taking rosuvastatin according to clinical studies and widespread post-registration use; Adverse reactions are grouped by frequency categories and organ system classes. The incidence of adverse reactions is presented as follows: often (≥ 1/100, but < 1/10); uncommon (≥ 1/1000, but < 1/100); rare (≥ 1/10000, but < 1/1000); very rare (< 1/10000), frequency unknown (cannot be estimated based on available data).

Table 2. Adverse reactions according to clinical studies and post-registration use

Interaction

Effect of concomitantly used drugs on rosuvastatin

Transport protein inhibitors: Rosuvastatin is a substrate for certain transport proteins, including the hepatic uptake transporter OATP1B1 and the efflux transporter BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in plasma concentrations of rosuvastatin and an increased risk of developing myopathy (see Table 1).

Cyclosporine: When rosuvastatin and cyclosporine were co-administered, rosuvastatin AUCs were, on average, 7 times higher than those observed in healthy volunteers (see Table 1). Crestor is contraindicated in patients concomitantly using cyclosporine. The simultaneous use of these drugs does not affect the concentration of cyclosporine in the blood plasma.

Protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant use with a protease inhibitor may result in a significant increase in rosuvastatin exposure (see Table 1). For example, in a pharmacokinetic study, coadministration of 10 mg rosuvastatin and a combination product containing two protease inhibitors (300 mg atazanavir/100 mg ritonavir) in healthy volunteers resulted in approximately three-fold and seven-fold increases in the AUC and maximum concentration (Cmax) of rosuvastatin, respectively. Concomitant use of Crestor and certain combinations of protease inhibitors is possible after careful assessment of the possibility of adjusting the dose of Crestor based on the expected increase in rosuvastatin exposure (see Table 1).

Gemfibrozil and other lipid-lowering drugs: the combined use of rosuvastatin and gemfibrozil led to a 2-fold increase in the maximum concentration of rosuvastatin in blood plasma and the AUC of rosuvastatin+.

Based on specific interaction studies, no significant pharmacokinetic interaction with fenofibrate is expected; pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and niacin (nicotinic acid) at lipid-lowering doses (≥ 1 g/day) increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, probably due to the fact that they can cause myopathy when used as monotherapy. Taking Crestor at a dose of 40 mg is contraindicated when co-administered with fibrates. Such patients should begin therapy with a dose of 5 mg.

Ezetimibe: concomitant use of Crestor 10 mg and ezetimibe 10 mg was associated with a 1.2-fold increase in rosuvastatin AUC in patients with hypercholesterolemia (see Table 1). A pharmacodynamic interaction between Crestor and ezetimibe in relation to adverse reactions cannot be excluded.

Antacids: simultaneous use of Crestor and an antacid in the form of a suspension containing magnesium and aluminum hydroxide led to a decrease in plasma concentrations of rosuvastatin by approximately 50%. This effect was less pronounced if the antacid was used 2 hours after taking Crestor. The clinical significance of this interaction has not been studied.

Erythromycin: simultaneous use of rosuvastatin and erythromycin led to a decrease in AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by erythromycin.

Cytochrome P450 isoenzymes: results from in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, interaction of rosuvastatin with other drugs at the metabolic level involving cytochrome P450 isoenzymes is not expected. There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 and CYP3A4 isoenzymes).

Drug interactions that require rosuvastatin dose adjustment (see Table 1)

The dose of Crestor should be adjusted if it is necessary to use it together with drugs that increase the exposure of rosuvastatin. If exposure is expected to increase by a factor of 2 or more, the initial dose of Crestor is 5 mg once daily. The maximum daily dose of Crestor should also be adjusted so that the expected exposure to rosuvastatin does not exceed that of a 40 mg dose taken without concomitant use of drugs that interact with rosuvastatin. For example, the maximum daily dose of Crestor when used simultaneously with gemfibrozil is 20 mg (increased exposure by 1.9 times), with ritonavir/atazanavir – 10 mg (increased exposure by 3.1 times).

No adjustment of the initial dose of Crestor is required if exposure is expected to increase by less than 2-fold; however, caution should be exercised when increasing the dose of Crestor above 20 mg.

Table 1. Effect of concomitant therapy on rosuvastatin exposure (AUC, data in descending order of exposure) – results from published clinical studies

Overdose

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

Storage conditions

At a temperature not exceeding 30 °C, out of the reach of children.

Shelf life

3 years. Do not use after the expiration date stated on the package.

Manufacturer

IPEr Pharmaceuticals Inc./AstraZeneca UK Limited, Puerto Rico