Tablets

- Substance-powder

- Tablets

- Tablets

- Tablets

- Tablets

- Tablets

- Tablets

- Tablets

- Tablets 10 mg; 20 mg; 40 mg

- Tablets

- Tablets

Indications for the use of the drug Crestor

Fredrickson's primary 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 inadequate;

Familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (eg, LDL apheresis), or in cases where such therapy is not effective enough;

Hypertriglyceridemia (Fredrickson type IV) as an adjunct to 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 (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 arterial hypertension, low concentration of HDL-C, smoking, family history of early onset of coronary artery disease).

Release form of the drug Crestor

film-coated tablets 10 mg; blister 7, cardboard pack 1;

Film-coated tablets 10 mg; blister 14, cardboard pack 2;

Film-coated tablets 20 mg; blister 7, cardboard pack 1;

Film-coated tablets 20 mg; blister 14, cardboard pack 2;

Film-coated tablets 40 mg; blister 7, cardboard pack 1;

Film-coated tablets 40 mg; blister 7, cardboard pack 4;

Film-coated tablets 5 mg; blister 14, cardboard pack 2;

Compound
Film-coated tablets 1 tab.
active substance:
rosuvastatin (as rosuvastatin calcium) 5 mg, 10 mg, 20 mg, 40 mg
excipients: lactose monohydrate; MCC; calcium phosphate; crospovidone; magnesium stearate
tablet shell: lactose monohydrate; hypromellose; triacetin (glycerol triacetate); titanium dioxide; iron dye yellow oxide (for tablets of 5 mg) or iron oxide red (for tablets of 10, 20, 40 mg)
in a blister 14 pcs.; in a cardboard pack 2 blisters (for tablets of 5, 20 mg) or in a blister 7 or 14 pcs.; in a cardboard pack 1 or 2 blisters, respectively (for tablets of 10 mg) or in a blister 7 pcs.; in a cardboard pack 4 blisters (for tab. 40 mg).

Pharmacodynamics of the drug Crestor

The lipid-lowering drug is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutarylcoenzyme A to mevalonate, a cholesterol precursor (Xc). The main target of rosuvastatin is the liver, where Xc synthesis and LDL catabolism are carried out.
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.
Crestor reduces elevated levels of LDL-Xc, total cholesterol, TG, increases the content of HDL-Xc, and also reduces the content of apolipoprotein B (ApoB), 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 ratio of ApoB / ApoA-1.
The therapeutic effect appears within 1 week after the start of Crestor therapy, after 2 weeks of treatment it reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by 4 weeks and is maintained with regular intake.
Crestor® is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, sex or age (including patients with diabetes mellitus and familial hypercholesterolemia). In 80% of patients with type IIa and IIb hypercholesterolemia (average initial LDL-C level is about 4.8 mmol/l), while taking the drug at a dose of 10 mg, the LDL-C level reaches values< 3 ммоль/л.
In patients with heterozygous familial hypercholesterolemia receiving Crestor® at a dose of 20-80 mg, there is a positive trend in lipid profile (a study involving 435 patients). After titration to a daily dose of 40 mg (12 weeks of therapy), there is a decrease in LDL-C by 53%. In 33% of patients, the level of Xc-LDL is achieved< 3 ммоль/л.
In patients with homozygous familial hypercholesterolemia taking Crestor® at a dose of 20 mg and 40 mg, the average decrease in LDL-C levels is 22%.
In patients with hypertriglyceridemia with an initial concentration of TG from 273 to 817 mg / dL, who received Crestor® at a dose of 5 mg to 40 mg once a day for 6 weeks, the level of TG in blood plasma was significantly reduced.
An additive effect is noted in combination with fenofibrate in relation to the content of TG and with nicotinic acid in relation to the content of HDL-C.
Studies on the effect of rosuvastatin in reducing the incidence of complications caused by lipid disorders, such as coronary artery disease, have not yet been completed.
In the METEOR study of 984 patients aged 45-70 years with low risk of developing coronary artery disease (10-year Framingham risk less than 10%), an average LDL-C level of 4 mmol/l (154.5 mg/dl) and subclinical atherosclerosis ( which was assessed by the thickness of the carotid intima-media complex - TIMT), the effect of rosuvastatin on TIMT was studied. Patients received rosuvastatin 40 mg/day or placebo for 2 years. Rosuvastatin therapy significantly slowed the rate of progression of maximal IMT for 12 segments of the carotid artery compared to placebo with a difference of -0.0145 mm/year. Compared with the baseline values ​​in the rosuvastatin group, there was a decrease in the maximum value of IMT by 0.0014 mm/year (0.12%/year, non-significant difference), compared with an increase in this indicator by 0.0131 mm/year (1.12%/year, p<0.001) в группе плацебо. До настоящего времени прямой зависимости между уменьшением ТКИМ и снижением риска сердечно-сосудистых событий продемонстрировано не было. Исследование METEOR проводилось у пациентов с низким риском ИБС, для которых доза препарата Крестор® 40 мг не является рекомендованной. Крестор® в дозе 40 мг следует назначать пациентам с выраженной гиперхолестеринемией и высоким риском сердечно-сосудистых заболеваний.

Pharmacokinetics of Crestor

Suction
Cmax of rosuvastatin in blood plasma is reached approximately 5 hours after oral administration. Absolute bioavailability is approximately 20%.
The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily intake.
Distribution
Rosuvastatin accumulates mainly in the liver. Vd - approximately 134 liters. Plasma protein binding (predominantly albumin) is approximately 90%.
Metabolism
Rosuvastatin undergoes limited metabolism (about 10%) in the liver. It is a non-core substrate for isoenzymes of the cytochrome P450 system. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. Isoenzymes CYP2C19, CYP3A4 and CYP2D6 are less involved in metabolism.
The main identified metabolites of rosuvastatin are N-dismethyl and lactone metabolites. N-desmethyl is about 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity of inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is its metabolites.
breeding
Approximately 90% of a dose of rosuvastatin is excreted unchanged in the feces. The rest is excreted in the urine. Plasma T1 / 2 - approximately 19 hours. T1 / 2 does not change with increasing doses of the drug. The mean plasma clearance is approximately 50 l/h (coefficient of variation 21.7%).
As with other HMG-CoA reductase inhibitors, the hepatic uptake of rosuvastatin involves the membrane carrier Xc, which plays an important role in the hepatic elimination of rosuvastatin.
Pharmacokinetics in special clinical situations
Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.
Pharmacokinetic studies have shown an approximately two-fold increase in the median AUC and Cmax of rosuvastatin in plasma in patients of Asian nationality (Japanese, Chinese, Filipinos, Vietnamese and Koreans), compared with Europeans; in Indian patients, an increase in the median AUC and Cmax by 1.3 times was shown. Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics between Europeans and representatives of the Negroid race.
In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-dismethyl does not change significantly.
In patients with severe renal insufficiency (CK<30 мл/мин) концентрация розувастатина в плазме крови в 3 раза выше, а концентрация N-дисметила в 9 раз выше, чем у здоровых добровольцев. Концентрация розувастатина в плазме крови у пациентов на гемодиализе была примерно на 50% выше, чем у здоровых добровольцев.
In patients with various stages of liver failure, an increase in T1 / 2 of rosuvastatin was not detected (patients with a score of 7 or lower on the Child-Pugh scale). In 2 patients with scores of 8 and 9 on the Child-Pugh scale, an increase in T1 / 2 was noted, at least 2 times. There is no experience with the use of rosuvastatin in patients with a score above 9 on the Child-Pugh scale.

Use of Crestor during pregnancy

Crestor® is contraindicated during pregnancy and lactation.

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 inhibition of HMG-CoA reductase outweighs the benefits of using the drug in pregnant women.

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

There are no data on the allocation of rosuvastatin with breast milk, therefore, during breastfeeding, the drug should be discontinued (see section "Contraindications").

Use of Crestor for Renal Impairment

Patients with mild or moderate renal insufficiency dose adjustment is not required. For patients with moderate renal impairment, an initial dose of 5 mg is recommended.
Contraindication: severe renal dysfunction (CC less than 30 ml / min).

Other special cases while taking Crestor

Contraindication: Active liver disease, including persistent elevation of serum transaminase activity and any elevation of serum transaminase activity (greater than 3 times ULN)

Contraindications to the use of Crestor

For 10 mg and 20 mg tablets
- severe impairment of kidney function (CC< 30 мл/мин);
- myopathy;
- pregnancy;

- predisposition to the development of myotoxic complications;

For 40 mg tablets
- 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 compared with VGN);
- simultaneous reception of cyclosporine;
- the presence of risk factors for the development of myopathy / rhabdomyolysis: moderate renal failure (CC< 60 мл/мин); гипотиреоз; личный или семейный анамнез мышечных заболеваний; миотоксичность на фоне приема других ингибиторов ГМГ-КоА-редуктазы или фибратов в анамнезе; чрезмерное употребление алкоголя; состояния, которые могут приводить к повышению плазменной концентрации розувастатина; одновременный прием фибратов; пациенты азиатской расы;
- pregnancy;
- lactation period (breastfeeding);
- lack of adequate methods of contraception;
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose);
- Hypersensitivity to the components of the drug.
With caution, use the drug in the form of tablets of 10 and 20 mg if there is a risk of developing myopathy / rhabdomyolysis - 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 excessive alcohol consumption; in patients over 65 years of age; conditions in which an increase in the plasma concentration of rosuvastatin is noted; in patients of Asian race; simultaneously with fibrates; with a history of liver disease; sepsis; arterial hypotension; extensive surgical interventions, injuries; with severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures.
Use the drug in the form of 40 mg tablets with caution in patients with mild renal insufficiency (CC more than 60 ml / min); over the age of 65; with a history of liver disease; sepsis; arterial hypotension; major surgery, trauma, severe metabolic, endocrine or electrolyte disturbances, or uncontrolled seizures.

Side effects of Crestor

Determining the frequency of adverse reactions: often (> 1/100,<1/10), иногда (>1/1000, <1/100), редко (>1/10 000, <1/1000), очень редко (<1/10 000), включая отдельные сообщения.
Allergic reactions: sometimes - urticaria; rarely - angioedema.
From the side of the central nervous system and peripheral nervous system: often - headache, dizziness.
From the digestive system: often - constipation, nausea, abdominal pain; sometimes - a slight, asymptomatic, transient increase in the activity of hepatic transaminases; rarely - pancreatitis.
Dermatological reactions: sometimes - itching, rash.
From the musculoskeletal system: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis with or without acute renal failure. A dose-dependent increase in CPK levels is observed in a small number of patients taking rosuvastatin. In most cases, it was minor, asymptomatic and temporary. In case of an increase in CPK more than 5 times higher than the upper limit of the norm, therapy should be suspended.
From the urinary system: proteinuria from trace amounts to "++" or more (<1% пациентов, получающих дозу 10-20 мг и около 3% пациентов, получающих дозу 40 мг). В большинстве случаев протеинурия уменьшается или исчезает в процессе терапии и не означает возникновения острого или прогрессирования существующего заболевания почек.
On the part of laboratory indicators: an increase in the content of glucose, bilirubin, GGT activity, alkaline phosphatase.
Others: often - asthenic syndrome; possible dysfunction of the thyroid gland.
Side effects observed when taking Crestor® are usually mild and disappear on their own.
As with other HMG-CoA reductase inhibitors, the incidence of side effects is dose-dependent. Side effects observed in post-marketing use
From the digestive system: very rarely - jaundice, hepatitis; rarely - increased activity of hepatic transaminases; unspecified frequency - diarrhea.
From the musculoskeletal system: very rarely - arthralgia.
From the side of the central nervous system: very rarely - polyneuropathy, memory loss.
From the urinary system: very rarely - hematuria.
Dermatological reactions: unspecified frequency - Stevens-Johnson syndrome.

Dosage and administration of Crestor

Inside, without chewing or crushing the tablet, swallowing whole, drinking water. The drug can be administered at any time of the day, regardless of food intake.

Prior to initiation of therapy with Crestor®, the patient should begin to follow a standard hypocholesterolemic diet and continue to follow it during treatment. The dose of the drug should be selected individually depending on the goals of therapy and the therapeutic response to treatment, taking into account current recommendations for target lipid concentrations.

The recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 or 10 mg of Crestor once a day. When choosing an initial dose, one should be guided by the individual cholesterol level and take into account the possible risk of cardiovascular complications, and it is also necessary to evaluate the potential risk of side effects. If necessary, the dose may be increased to a higher dose 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 (see the section "Side effect"), increasing the dose to 40 mg, after taking an additional dose above the recommended initial dose for 4 weeks of therapy, can only be performed in patients with severe hypercholesterolemia and at high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia), who have not achieved the desired result of therapy with a dose of 20 mg, and who will be under the supervision of a specialist (see. section "Special Instructions"). Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

It is not recommended to prescribe 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 Crestor, monitoring of lipid metabolism is necessary (if necessary, dose adjustment is required).

Elderly patients

Dose adjustment is not required.

Patients with renal insufficiency

In patients with mild or moderate renal insufficiency, dose adjustment is not required. In patients with severe renal insufficiency (Cl creatinine less than 30 ml / min), the use of Crestor® is contraindicated. The use of the drug at a dose of 40 mg is contraindicated in patients with moderately impaired renal function (Cl creatinine 30-60 ml / min.) (see section "Special Instructions"). For patients with moderate renal impairment, an initial dose of 5 mg is recommended.

Patients with liver failure

Crestor® is contraindicated in patients with active liver disease (see section "Contraindications").

special populations. ethnic groups

When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin among the Japanese and Chinese was noted (see section "Special Instructions"). This fact should be taken into account when prescribing Crestor® to these groups of patients. When prescribing doses of 10 and 20 mg, the recommended initial dose for patients of the Mongoloid race is 5 mg. The appointment of the drug at a dose of 40 mg to patients of the Mongoloid race is contraindicated (see section "Contraindications").

Patients predisposed to myopathy

The appointment of the drug at a dose of 40 mg is contraindicated in patients with factors that may indicate a predisposition to the development of myopathy (see section "Contraindications"). When prescribing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg (see section "Contraindications")

Overdose of Crestor

With the simultaneous administration of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.

Treatment: 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. Monitoring of liver function and CPK levels is necessary. It is unlikely that hemodialysis will be effective.

Interactions of the drug Crestor with other drugs

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. Joint use leads to an increase in the concentration of rosuvastatin in the blood plasma by 11 times, while the plasma concentration of cyclosporine does not change.
Starting therapy with rosuvastatin or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in prothrombin time (an increase in INR). Cancellation of rosuvastatin or a decrease in its dose may lead to 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 plasma Cmax and AUC of rosuvastatin. Based on specific interaction data, a pharmacokinetically significant interaction with fenofibrates is not expected, a pharmacodynamic interaction is possible.
Gemfibrozil, other fibrates and lipid-lowering doses of nicotinic acid increased the risk of myopathy when used simultaneously with other HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used as monotherapy.
While taking the drug with gemfibrozil, fibrates, nicotinic acid at a dose of more than 1 g / day, patients are recommended an initial dose of 5 mg.
The simultaneous use of the drug Crestor® and ezetimibe was not accompanied by a change in the AUC and Cmax of both drugs.
Although the exact mechanism of interaction is unknown, the co-administration of protease inhibitors can lead to a significant increase in the exposure of rosuvastatin. A pharmacokinetic study on the simultaneous use of 20 mg rosuvastatin with a combination preparation containing two protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in an approximately two-fold and five-fold increase in AUC (0-24) and Cmax of rosuvastatin, respectively. Therefore, concomitant use of rosuvastatin and protease inhibitors is not recommended in the treatment of patients with HIV.
The simultaneous use of rosuvastatin and antacids containing aluminum and magnesium hydroxide leads to a decrease in 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.
The simultaneous use of rosuvastatin and erythromycin leads to a decrease in AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%, probably as a result of increased intestinal motility caused by taking erythromycin.
The simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinylestradiol and the AUC of norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when selecting a dose of oral contraceptives against the background of the use of Crestor. Pharmacokinetic data on the simultaneous use of Crestor and hormone replacement therapy are not available, therefore, a similar effect cannot be excluded when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.
No clinically significant interaction of rosuvastatin with digoxin is expected.
The results of in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of isoenzymes of the cytochrome P450 system. In addition, rosuvastatin is a weak substrate for these enzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4). The combined use of rosuvastatin and itraconazole (a CYP3A4 inhibitor) increases the AUC of rosuvastatin by 28% (clinically insignificant). Thus, an interaction associated with the cytochrome P450 system is not expected.

Special instructions for taking Crestor

When using Crestor at a dose of 40 mg, it is recommended to monitor indicators of kidney function.
With the use of the drug Crestor® in all doses, especially more than 20 mg, the development of myalgia, myopathy and, in rare cases, rhabdomyolysis has been reported.
The determination of CPK should not be carried out after intense physical exertion or in the presence of other possible reasons for the increase in CPK, which may lead to an incorrect interpretation of the results. If the initial level of CPK is significantly increased (5 times higher than the upper limit of the norm), after 5-7 days a second measurement should be taken. You should not start therapy if a repeat test confirms the initial level of CPK (5 times higher than ULN).
When prescribing Crestor® (as well as other HMG-CoA reductase inhibitors) in patients with existing risk factors for rhabdomyolysis, it is necessary to consider the ratio of expected benefit and potential risk and conduct clinical observation.
The patient should be informed about the need to immediately inform 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 CPK should be determined. Therapy should be discontinued if the level of CPK is significantly increased (more than 5 times compared with ULN) or if muscle symptoms are pronounced and cause daily discomfort (even if the level of CPK is 5 times lower than ULN). If symptoms disappear and CPK levels return to normal, consideration should be given to re-prescribing Crestor or other HMG-CoA reductase inhibitors at lower doses with careful monitoring of the patient.
Routine monitoring of CPK in the absence of symptoms is impractical.
There were no signs of an increase in toxic effects on skeletal muscles when using Crestor® as part of combination therapy. An increase in the 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, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Thus, the simultaneous administration of Crestor® and gemfibrozil is not recommended. The ratio of expected benefit and potential risk should be carefully weighed when using Crestor® and fibrates or niacin together.
After 2-4 weeks after the start of treatment and / or with an increase in the dose of Crestor®, monitoring of lipid metabolism is necessary (if necessary, dose adjustment is required).
It is recommended to determine the parameters of liver function before the start of therapy and 3 months after the start of therapy. Reception of the drug Crestor® should be discontinued or the dose of the drug should be reduced if the level of activity of transaminases in the blood serum is 3 times the upper limit of the norm.
In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of underlying diseases should be carried out before starting treatment with Crestor®.
Clinical experience and data on the use of the drug in patients with impaired liver function, corresponding to more than 9 points on the Child-Pugh scale, are not available.
Pediatric use
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. The use of Crestor® in children and adolescents under 18 years of age is not currently recommended.
Influence on the ability to drive vehicles and control mechanisms
No studies have been conducted to study the effect of Crestor® on the ability to drive vehicles and work with mechanisms. Based on pharmacodynamic properties, Crestor® is not expected to have such an effect.
Patients should be careful when driving vehicles or work that requires increased concentration and speed of psychomotor reaction, because. dizziness may occur during therapy.

Storage conditions of the drug Crestor

List B.: At a temperature not higher than 30 °C.

Shelf life of Crestor

Crestor belongs to the ATX classification:

C Cardiovascular system

C10 Lipid-lowering drugs

C10A Cholesterol and hypotriglyceridemic drugs

C10AA HMG-CoA reductase inhibitors

Manufacturer:

AstraZeneca UK

Active ingredients of Crestor:

Rosuvastatin

Crestor release form:

• Coated tablets, 10 mg № 28 (14x2)
• Coated tablets, 20 mg № 28 (14x2)
• Coated tablets, 40 mg No. 28 (7x4).

Who is shown the Crestor?

Primary 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 inadequate.

Homozygous familial hypercholesterolemia as an adjunct to diet and other cholesterol-lowering therapy (eg, LDL apheresis) or when such therapy is not appropriate for the patient.

How to use Crestor?

Before starting treatment, the patient should be prescribed a standard lipid-lowering diet, which he must adhere to during treatment with Crestor. The dose should be selected individually depending on the purpose of therapy and the response to treatment, guided by recommendations for target lipid levels.

The recommended starting dose for patients who are starting treatment with the drug or who are being transferred from taking other HMG-CoA reductases should be 5 or 10 mg per day. The choice of starting dose should be guided by individual cholesterol levels and take into account the risk of cardiovascular complications in the future, as well as the risk of adverse events. If necessary, the dose can be increased to the next one no earlier than 4 weeks later. Due to the increased risk of adverse events when taking Crestor 40 mg compared with lower doses, an increase in dose to 40 mg is possible after 4 weeks of treatment only in patients with severe hypercholesterolemia and a high risk of developing cardiovascular complications (especially in patients with familial hypercholesterolemia) who did not achieve the desired result with the use of 20 mg and who will be under the close supervision of specialists. Special control is recommended at the beginning of taking 40 mg of the drug.

Crestor is taken orally without chewing, the tablet is swallowed whole with water. Crestor can be taken at any time with or without food.

Elderly patients

Dose adjustment is not required.

Patients with renal insufficiency

Patients with mild renal insufficiency do not require dose adjustment. Patients with moderate renal insufficiency should begin treatment with Crestor at 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 - 20 mg.

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

The 40 mg dose is contraindicated in patients with moderate renal impairment (creatinine clearance

Patients with liver failure

There is no experience of using the drug in patients with hepatic insufficiency with a score above 9 on the Child-Pugh scale. Crestor is contraindicated in patients with active liver disease.

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 start treatment with a dose of 5 mg. The 40 mg dose is contraindicated. The maximum daily dose is 20 mg.

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

The starting dose for these patients is 5 mg. The 40 mg dose is contraindicated. The maximum daily dose is 20 mg.

Before starting treatment.

Crestor, like other HMG-CoA reductase inhibitors, should be used with caution in patients who are prone to developing myopathy/rhabdomyolysis. Risk factors may be:

• kidney failure;
• hypothyroidism;
• myotoxicity caused by taking inhibitors of HMG-CoA reductase or fibrates in history;
• alcohol abuse;
• age over 70 years;

In such cases, the risk-benefit ratio of treatment should be considered, and such patients should be carefully monitored. If the level of CPK 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 about the need to immediately inform 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 CPK should be determined. Treatment should be discontinued if the CPK level is significantly increased (5 times or more compared to the upper limit of normal) or if muscle symptoms are pronounced and cause daily discomfort (even if the CPK level does not reach a 5-fold increase compared to the upper limit norms). If symptoms disappear and CPK levels return to physiological levels, the possibility of re-prescribing Crestorau or other HMG-CoA reductase inhibitors at lower doses should be considered. The patient should be closely monitored. Routine monitoring of CPK in the absence of symptoms is impractical. In clinical studies, there were no signs of an increase in the effect on skeletal muscles when taking Crestor and concomitant therapy. However, an increase in the incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors concomitantly with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid, azole antifungals, protease inhibitors, and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when administered concomitantly with certain HMG-CoA reductase inhibitors. Therefore, it is not recommended to prescribe Crestor and gemfibrozil at the same time. The risk-benefit ratio should be carefully assessed when Crestor and fibrates or niacin are given concomitantly.

The simultaneous use of Crestor at a dose of 40 mg with fibrates is contraindicated.

Crestor should be prescribed to patients with acute severe conditions such as sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine or electrolyte disturbances, or uncontrolled epilepsy, which may be risk factors for the development of myopathy / rhabdomyolysis.

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

Influence on skeletal muscles. Skeletal muscle effects such as myalgia, myopathy and, rarely, rhabdomyomysis have been observed with Crestor treatment (especially at doses >20 mg).

Determination of creatine phosphokinase (CPK). The determination of CPK should not be carried out after intense physical exertion or in the presence of other probable reasons for the increase in CPK, which may lead to incorrect interpretation of the results. In the case when the initial level of CPK is increased (5 times higher than the upper limit of normal), a second test should be carried out after 5 to 7 days. You should not start therapy if a repeat test confirms the output high level of CPK (5 times higher than the upper limit of normal).

Children. Efficacy and safety of use in children have not been established. Experience in pediatric practice is limited to a small number of children (aged 8 years and older) with familial homozygous hypercholesterolemia. It is not recommended to prescribe Crestor to children.

Side effects of Crestor.

Adverse events that were observed during treatment with Crestor were moderately severe and passed on their own. Treatment discontinuation rates due to adverse events in clinical trials were less than 4%. The incidence of adverse events was assessed on the following scale: often (1/100, 1/1000, 1/10,000,

• From the side of the immune system
  caustic: hypersensitivity reactions, including angioedema.
• From the side of the nervous system
  Often: headache, dizziness.
• From the gastrointestinal tract
  Often: constipation, nausea, abdominal pain.
• From the skin and appendages
  Infrequently: itching, rash and urticaria.
• From the musculoskeletal system
  • Often: myalgia.
  • Rare: myopathy and rhabdomyolysis.
• General violations
  Often: asthenia.

As with other HMG-CoA reductase inhibitors, the incidence of adverse events is dose-dependent.

• From the urinary system: patients taking Crestor may have proteinuria, mainly tubular. A change in the amount of protein in the urine (from no to traces or to + + or more) was observed in
• From the side of skeletal muscles: myalgia, myopathy and rarely rhabdomyolysis were observed in patients who took all doses and especially in those who took the drug at a dose of more than 20 mg.
• A dose-dependent increase in the level of creatine phosphokinase (CPK) was observed in patients taking rosuvastatin, and in most cases it was insignificant, asymptomatic and temporary. With an increase in the level of CPK (5 or more times compared to the upper limit of the norm), rosuvastatin therapy should be suspended.
• On the part of the liver: as with other HMG-CoA reductase inhibitors, a dose-dependent increase in transaminase activity was observed in a small number of patients. In most cases, it was minor, asymptomatic and temporary.

In addition to the above, after the introduction of the drug into wide medical practice, the following phenomena were observed:

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

Who is not suitable for Crestor?

• Hypersensitivity to rosuvastatin or any component of the tablet;
• liver disease in the active phase, including a persistent increase in transaminase activity that cannot be explained, and any increase in transaminase activity 3 or more times compared with the upper limit of normal;
• severe impairment of renal function (creatinine clearance
• myopathy;
• simultaneous use of cyclosporine;
• pregnancy and lactation;
• the drug is not prescribed to women who do not use adequate contraceptives;
• age up to 18 years.

The 40 mg dose is contraindicated in patients who are at increased risk for myopathy/rhabdomyolysis. These factors are:

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

Crestor interaction.

Cyclosporine: With the simultaneous use of rosuvastatin and cyclosporine, the area under the concentration-time curve (AUC) of rosuvastatin was on average 7 times greater than that obtained in healthy volunteers. Simultaneous use does not affect the concentration of cyclosporine in plasma.

Vitamin K antagonists: as with other HMG-CoA reductase inhibitors, at the beginning of therapy and with an increase in the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin), an increase in prothrombin time (INR - International Normalized Ratio) may be observed. drug or dose reduction may lead to a decrease in INR.In such cases, monitoring of INR is recommended.

Gemfibrozil and other lipid-lowering agents: the simultaneous use of rosuvastatin and gemifibrozil leads to an increase in the maximum plasma concentration of rosuvastatin (Cmax) and AUC of rosuvastatin by a factor of two. Pharmacokinetic interactions with fibrates are not expected, but pharmacodynamic interactions are possible. Gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses of nicotinic acid (large or equivalent doses of 1 g/day) increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause the development of myopathy and with their use as monotherapy. Such patients are recommended to start therapy with a dose of 5 mg per day.

Crestor is a synthetic drug used to lower cholesterol levels.

Release form

Crestor is produced in the form of tablets containing the active ingredient - rosuvastatin, in the amount of 5 mg, 10 mg (Crestor 10), 20 mg and 40 mg. 7 and 14 tablets per pack.

Crestor's analogs

Crestor's analogues for the active substance include Acorta, Mertenil, Rosuvastatin, Rosulip, Roxera, Tevastor and Rosucard.

According to the mechanism of action, Crestor analogues are tablets Atomax, Lipona, Vazator, Actalipid, Leskol, Choletar, Atoris, Zocor, Simvastatin, Torvacard, Medostatin, Liptonorm, Anvist, Zorstat, Lipoford, Cardiostatin, Lovastatin, Simlo, Sinkard, Pravastatin, Simvalimit and Ovencor .

Pharmacological action of Crestor

The active ingredient in Crestor (rosuvastatin) is an enzyme that converts to mevalonic acid, which is a cholesterol precursor. The effect of the drug is directed to the liver, where cholesterol is synthesized.

The therapeutic effect of taking Crestor develops during the first week of treatment, and the maximum effect is achieved within 2-4 weeks of regular use.

Indications for the use of Crestor

Crestor is prescribed as an adjunct to a diet when traditional therapy, including exercise and weight loss measures, fails in the treatment of:

• Primary hypercholesterolemia according to Fredrickson (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb);
• Familial homozygous hypercholesterolemia;
• Hypertriglyceridemia (type IV according to Fredrickson).

Crestor is also prescribed:

• As an addition to a diet to slow the development of atherosclerosis;
• To reduce the risk of major cardiovascular complications - stroke, heart attack, unstable angina and arterial revascularization in the presence of increased risk factors for such complications;
• As a primary prevention of major cardiovascular complications (without clinical manifestations of coronary heart disease, but with a risk of its development - smoking, hypertension, family history).

Contraindications

Contraindications for the use of Crestor according to the instructions are:

• Liver diseases occurring in the active phase;
• myopathy;
• Severe disorders of kidney function;
• Pregnancy;
• Lack of adequate methods of contraception in women;
• Simultaneous reception with cyclosporine;
• lactation period;
• Predisposition to the development of myotoxic complications;
• Hypersensitivity to the main (rosuvastatin) or auxiliary components of the drug.

Crestor is not used in pediatrics (under 18 years of age). In addition, Crestor at a daily dose of 40 mg is also contraindicated to take:

• With a personal or family history of muscle disease;
• People of the Mongoloid race;
• Against the background of hypothyroidism;
• With excessive alcohol consumption;
• With myotoxicity while taking fibrates or other medications with a similar therapeutic effect;
• Simultaneously with the reception of fibrates;
• In conditions leading to an increase in the concentration of the active substance (rosuvastatin) in the blood plasma.

Caution should be taken in a daily dosage of 5 mg, 10 mg and 20 mg Crestor:

• With excessive alcohol consumption;
• Against the background of the existing risk of developing myopathy, which usually occurs with hypothyroidism, renal failure and hereditary muscle diseases;
• Against the background of arterial hypotension;
• Simultaneously with fibrates;
• Elderly people (from 65 years old) and people of the Mongoloid race;
• With sepsis;
• Against the background of liver disease in history;
• With extensive surgical interventions, uncontrolled seizures, trauma, severe endocrine, metabolic or electrolyte disorders.

At a daily dose of 40 mg, Crestor is prescribed with caution against the background of mild hepatic and renal failure, sepsis, arterial hypotension.

Method of application and dosage

Crestor tablets should be swallowed whole, and the time of administration does not affect the effectiveness of the medication. Before starting treatment, you must follow the usual hypocholesterolemic diet, which must be followed throughout the course of therapy.

The dose of Crestor, depending on the goals of therapy, the doctor selects individually. Typically, the standard starting dose is 5 mg or 10 mg (1 Crestor 10 tablet) per day.

The choice of the initial dose is influenced by the level of cholesterol and the risk of developing cardiovascular complications, as well as the potential risk of developing undesirable effects. If the initial dose was 5 mg, the daily dose to 1 tablet of Crestor 10 can be increased no earlier than a month later.

A dosage of 40 mg is considered undesirable due to the high risk of side effects. It is prescribed only for severe hypercholesterolemia and in the presence of a high risk of cardiovascular complications. When taking the drug at this dosage, lipid metabolism should be carefully monitored, and if necessary, a dose adjustment should be made.

Dose adjustments should not be made in the elderly. Against the background of mild or moderate renal insufficiency, Crestor at a dose of 40 mg is not prescribed, and the initial dosage should not exceed 5 mg. Against the background of liver failure, Crestor in any dosage is contraindicated. Against the background of a predisposition to myopathy, the dosage rarely exceeds 1 tablet of Crestor 10.

drug interaction

Before taking Crestor together with other medicines, it is necessary to consult a doctor, since many drug combinations are unsafe and can lead to a violation of the therapeutic effect and the development of many undesirable effects.

Side effects of Crestor

As a rule, Crestor, according to reviews, causes side effects in rare cases. At the same time, most studies note their short-term and mild nature.

So, when using Crestor, according to reviews. possible development:

• Hypersensitivity reactions, including the development of angioedema (immune system);
• Type 2 diabetes mellitus (endocrine system);
• Headache and dizziness (central nervous system);
• Nausea, constipation and pain in the abdomen (gastrointestinal tract);
• Rash, pruritus and urticaria (skin);
• Myalgia, myopathy, rhabdomyolysis (musculoskeletal system);
• Proteinuria (urinary system).

Based on the results of a post-marketing study, it was found that, according to some reviews, Crestor can cause:

• Jaundice and hepatitis;
• arthralgia;
• diarrhea
• cough and shortness of breath;
• Polyneuropathy and memory loss;
• peripheral edema;
• Hematuria;
• Stevens-Johnson Syndrome.

In isolated cases, the use of Crestor led to the development of depression, nightmares, sleep disturbances, sexual dysfunctions, and insomnia.

In case of an overdose of Crestor, according to the instructions, symptomatic treatment should be carried out with monitoring of liver function.

The page contains instructions for use Crestor. It is available in various dosage forms of the drug (tablets 5 mg, 10 mg, 20 mg and 40 mg), and also has a number of analogues. This annotation has been verified by experts. Leave your feedback about the use of Crestor, which will help other site visitors. The drug is used for various diseases (hypercholesterolemia and lowering cholesterol levels in the blood). The tool has a number of side effects and features of interaction with other substances. Doses of the drug differ for adults and children. There are restrictions on the use of the drug during pregnancy and during breastfeeding. Treatment with Crestor can only be prescribed by a qualified doctor. The duration of therapy may vary and depends on the specific disease. Composition and interaction of statin with alcohol.

Instructions for use and dosage

Inside, do not chew or crush the tablet, swallow it whole with water. The drug can be administered at any time of the day, regardless of food intake. Prior to initiating therapy with Crestor, the patient should begin to follow a standard cholesterol-lowering diet and continue to follow it during treatment. The dose of the drug should be selected individually depending on the goals of therapy and the therapeutic response to treatment, taking into account current recommendations for target lipid concentrations.

The recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 or 10 mg of Crestor 1 time per day. When choosing an initial dose, one should be guided by the individual concentration of cholesterol and take into account the possible risk of cardiovascular complications, and it is also necessary to evaluate the potential risk of side effects. If necessary, the dose may be increased to a higher dose after 4 weeks.

Due to the possible development of side effects when taken at a dose of 40 mg, compared with lower doses of the drug, an increase in dose to 40 mg, after an additional dose 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 have not achieved the desired result of therapy when taking a dose of 20 mg, and who will be under the supervision of a specialist. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

It is not recommended to prescribe the drug at 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 Crestor, monitoring of lipid metabolism is necessary (if necessary, dose adjustment is required).

Elderly patients do not require dose adjustment.

In patients with mild or moderate renal insufficiency, dose adjustment is not required. In patients with severe renal insufficiency (CC less than 30 ml / min), the use of Crestor is contraindicated. The use of the drug at a dose of 40 mg is contraindicated in patients with moderate renal impairment (CC 30-60 ml / min). For patients with moderate renal impairment, an initial dose of 5 mg is recommended.

Patients with hepatic impairment: Crestor is contraindicated in patients with active liver disease.

Compound

Rosuvastatin (in the form of calcium salt) + excipients.

Release forms

Film-coated tablets 5 mg, 10 mg, 20 mg and 40 mg.

Crestor- a lipid-lowering drug, a selective competitive inhibitor of HMG-CoA reductase.

Crestor reduces elevated concentrations of LDL cholesterol (LDL-C), total cholesterol, triglycerides (TG), increases the concentration of high-density lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (ApoB), non-HDL-C, cholesterol- VLDL, TG-VLDL, reduces the ratio of LDL-C/HDL-C, total C/HDL-C and non-HDL-C/HDL-C and ApoB/ApoA-1 ratio.

The therapeutic effect develops within one week after the start of therapy with Crestor, after 2 weeks of treatment it reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with regular use of the drug.

Crestor is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia; regardless of race, gender or age, incl. in patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia type 2a and 2b according to Fredrickson (the average initial concentration of LDL-C is about 4.8 mmol / l), while taking the drug at a dose of 10 mg, the concentration of LDL-C reaches values ​​less than 3 mmol / l.

In patients with heterozygous familial hypercholesterolemia receiving Crestor at a dose of 20-80 mg, there is a positive trend in lipid profile parameters (a study involving 435 patients). After titration to a daily dose of 40 mg (12 weeks of therapy), there is a decrease in the concentration of LDL-C by 53%. In 33% of patients, the concentration of LDL-C is less than 3 mmol / l.

The results of the JUPITER study (Rationale for the use of statins for primary prevention: an intervention study evaluating rosuvastatin) in 17802 patients showed that rosuvastatin (the active ingredient in Crestor) significantly reduced the risk of developing cardiovascular events (252 in the placebo group compared with 142 in the placebo group rosuvastatin) (p less than 0.001) with a relative risk reduction of 44%. The effectiveness of therapy was noted after the first 6 months of using the drug. There was a statistically significant reduction of 48% in the combined criterion of death from cardiovascular causes, stroke and myocardial infarction (hazard ratio 0.52, 95% confidence interval 0.40-0.68, p less than 0.001), a 54% reduction in the incidence of fatal or non-fatal myocardial infarction (hazard ratio: 0.46, 95%, confidence interval 0.30-0.70) and 48% fatal or non-fatal stroke. Overall mortality decreased by 20% in the rosuvastatin group (hazard ratio: 0.80, 95%, confidence interval 0.67-0.97, p=0.02). The safety profile in patients treated with rosuvastatin 20 mg was generally similar to the safety profile in the placebo group.

Pharmacokinetics

Rosuvastatin is metabolized primarily by the liver, which is the main site for cholesterol synthesis and LDL-C metabolism. Vd of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.

About 90% of a dose of rosuvastatin is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin). The rest is excreted by the kidneys. As in the case of other inhibitors of HMG-CoA reductase, the membrane cholesterol transporter is involved in the process of "hepatic" uptake of rosuvastatin, which plays an important role in the hepatic elimination of rosuvastatin.

The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily intake.

Age and gender do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.

Indications

• primary hypercholesterolemia according to Fredrickson (type 2a, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type 2b) as an adjunct to diet when diet and other non-drug treatments (eg, exercise, weight loss) are insufficient;
• familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (eg, LDL apheresis), or in cases where such therapy is not effective enough;
• hypertriglyceridemia (Fredrickson type 4) as an adjunct to 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 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 ( more than 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low concentration of HDL-C, smoking, family history of early onset of coronary artery disease).

Contraindications

For the drug Crestor in a daily dose of 5 mg, 10 mg and 20 mg:

• severe renal dysfunction (CC less than 30 ml / min);
• myopathy;
• patients predisposed to the development of myotoxic complications.

For the drug Crestor in a daily dose of 40 mg:

• hypersensitivity to rosuvastatin or any of the components of the drug;
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose);
• children and adolescents up to 18 years of age;
• simultaneous reception of cyclosporine;
• in women: pregnancy, lactation, lack of adequate methods of contraception;
• 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 compared with VGN);
• patients with risk factors for the development of myopathy / rhabdomyolysis, namely: moderate renal failure (CC less than 60 ml / min), hypothyroidism, personal or family history of muscle diseases, myotoxicity while taking other HMG-CoA reductase inhibitors or a history of fibrates;
• excessive alcohol consumption;
• conditions that can lead to an increase in the plasma concentration of rosuvastatin;
• simultaneous reception of fibrates;
• Mongoloid patients.

special instructions

Effect on the kidneys

In patients receiving high doses of Crestor (mainly 40 mg), tubular proteinuria was observed, which, in most cases, was transient. Such proteinuria was not indicative of acute kidney disease or progression of kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor indicators of kidney function during treatment.

From the side of the musculoskeletal system

When using Crestor at all doses, especially at doses greater than 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy, in rare cases, rhabdomyolysis.

Definition of CPK

Determination of the level of CPK 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 an incorrect interpretation of the results. If the initial level of CPK is significantly increased (5 times higher than the upper limit of the norm), after 5-7 days a second measurement should be taken. You should not start therapy if a repeat test confirms the initial activity of CPK (more than 5 times higher than ULN).

Before starting therapy

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

During therapy

The patient should be informed about the need to immediately inform the doctor about cases of sudden 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 increased (more than 5 times compared to ULN) or if muscle symptoms are pronounced and cause daily discomfort (even if CPK activity is 5 times less compared to ULN).

If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Crestor or other HMG-CoA reductase inhibitors at lower doses with careful monitoring of the patient.

Routine monitoring of CPK activity in the absence of symptoms is impractical. There have been 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 serum CK levels during treatment or when statins are discontinued, incl. rosuvastatin. Additional studies of the muscular system and nervous system, serological studies, as well as immunosuppressive therapy may be required.

There were no signs of increased skeletal muscle exposure with Crestor and concomitant therapy. However, an increase in the 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, nicotinic acid, azole antifungals, protease inhibitors, and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Thus, the simultaneous use of Crestor and gemfibrozil is not recommended. The risk-benefit ratio should be carefully weighed when Crestor is co-administered with fibrates or lipid-lowering doses of nicotinic acid. It is contraindicated to take the drug Crestor at a dose of 40 mg in conjunction with fibrates. 2-4 weeks after the start of treatment and / or with an increase in the dose of Crestor, monitoring of lipid metabolism is necessary (if necessary, dose adjustment is required).

Liver

It is recommended to carry out the determination of indicators of liver function before the start of therapy and 3 months after the start of therapy. Reception of the drug Crestor should be discontinued or the dose of the drug should be reduced if the activity of transaminases in the blood serum: 3 times the upper limit of the norm.

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

HIV protease inhibitors

Lactose

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

interstitial lung disease

With the use of some statins, especially for a long time, isolated cases of interstitial lung disease have been reported. Symptoms of the disease may include shortness of breath, non-productive cough and deterioration in 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 mellitus.

Influence on the ability to drive vehicles and control mechanisms

No studies have been conducted to study the effect of the drug Crestor on the ability to drive a vehicle and use mechanisms. Care should be taken when driving vehicles or work that requires increased concentration and speed of psychomotor reactions (during therapy, dizziness may occur).

Side effect

• hypersensitivity reactions, including angioedema;
• type 2 diabetes;
• headache;
• dizziness;
• constipation;
• diarrhea;
• nausea;
• stomach ache;
• pancreatitis;
• skin itching;
• rash;
• hives;
• myalgia;
• myopathy (including myositis);
• rhabdomyolysis;
• proteinuria;
• hematuria;
• asthenic syndrome;
• arthralgia;
• polyneuropathy;
• memory loss;
• cough;
• dyspnea;
• Stevens-Johnson syndrome;
• gynecomastia;
• peripheral edema.

drug interaction

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. Joint use leads to an increase in the concentration of rosuvastatin in plasma, blood by 11 times. Does not affect the plasma concentration of cyclosporine.

Indirect anticoagulants: the beginning of Crestor therapy or an increase in the dose of the drug in patients receiving concomitant indirect anticoagulants (for example, warfarin) may lead to an increase in prothrombin time (MHO). Cancellation of rosuvastatin or a decrease in the dose of the drug may lead to a decrease in MHO. In such cases, MHO monitoring is recommended.

Gemfibrozil and other lipid-lowering agents: The combined use of rosuvastatin and gemfibrozil results in a 2-fold increase in Cmax of rosuvastatin in blood plasma and AUC of rosuvastatin. Based on specific interaction data, a pharmacokinetically significant interaction with fenofibrates is not expected, a pharmacodynamic interaction is possible.

Gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses of nicotinic acid increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used as monotherapy. While taking the drug with gemfibrozil, fibrates, nicotinic acid at a dose of more than 1 g per day, patients are recommended an initial dose of 5 mg.

Ezetimibe: The simultaneous use of Crestor and ezetimibe was not accompanied by a change in the AUC and Cmax of both drugs.

HIV protease inhibitors: Although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in exposure to rosuvastatin.

A pharmacokinetic study on the simultaneous use of 20 mg rosuvastatin with a combination preparation containing two HIV protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers resulted in an approximately two-fold and five-fold increase in AUC0-24 and Cmax of rosuvastatin, respectively. Therefore, the simultaneous use of rosuvastatin and HIV protease inhibitors in the treatment of patients with HIV infection is not recommended.

Antacids: The simultaneous use of rosuvastatin and suspensions of antacids containing aluminum and magnesium hydroxide leads to a decrease in 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: The simultaneous use of Crestor and erythromycin leads to a decrease in AUC0-24 of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by erythromycin.

Oral contraceptives / hormone replacement therapy: The simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinylestradiol and the AUC of norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when selecting a dose. Plasma concentration should be taken into account when selecting a dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of Crestor and hormone replacement therapy are not available, therefore, a similar effect cannot be excluded when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medicinal products: no clinically significant interaction of rosuvastatin with digoxin is expected.

Cytochrome P450 isoenzymes: The results of 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 enzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4 isoenzymes). The combined use of rosuvastatin and itraconazole (an inhibitor of the CYP3A4 isoenzyme) increases the AUC of rosuvastatin by 28% (clinically insignificant). Thus, an interaction associated with cytochrome P450 metabolism is not expected.

Crestor's analogues

Structural analogues for the active substance:

• Acorta;
• Mertenil;
• Rosuvastatin;
• Rosucard;
• Rosulip;
• Roxer;
• Tevastor.

Analogues by pharmacological group (statins):

• Acorta;
• Actalipid;
• Anvist;
• Apexstatin;
• Atherostat;
• Atocord;
• Atomax;
• Atorvastatin;
• Atorvox;
• Atoris;
• Vasator;
• Vasilip;
• Zokor;
• Zokor forte;
• Zorstat;
• Cardiostatin;
• Leskol;
• Leskol forte;
• Lipobai;
• Lipostat;
• Lipoford;
• Liprimar;
• Liptonorm;
• Lovakor;
• Lovastatin;
• Lovasterol;
• Mevacor;
• medostatin;
• Mertenil;
• Ovencor;
• Pravastatin;
• Rovakor;
• Simvacard;
• Simvakol;
• Simvalimit;
• Simvastatin;
• Simvastol;
• Symbol;
• Simgal;
• Simlo;
• Sincard;
• Torvasin;
• Torvacard;
• Tulip;
• Holvasim;
• Choletar.

Use in children

Contraindicated in children and adolescents under the age of 18 years (the effect on this age group has not been studied).

Use in elderly patients

Dose adjustment is not required. Care must be taken.

Use during pregnancy and lactation

Crestor is contraindicated during pregnancy and lactation (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 inhibition of HMG-CoA reductase outweighs the benefits of using the drug in pregnant women.

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

There are no data on the excretion of rosuvastatin in breast milk, therefore, during breastfeeding, the drug should be discontinued.

Statins are a type of drugs that suppress the production of enzymes in the liver that are responsible for the formation of cholesterol. The drugs inhibit the activity of the HMG-CoA reductase enzyme, which provokes the production of cholesterol in the liver, thereby improving blood circulation. The combined use of statins and alcohol can cause both a sharp increase in the properties of the drug, and a complete annulment of the therapeutic effect.

Mechanisms of interaction when combined

The accumulation of lipophilic alcohol in the body leads to the formation of atherosclerotic plaques, obstruction of blood flow through the vessels, and the development of cardiovascular diseases. Alcoholism, along with high blood cholesterol, only exacerbates the situation, increasing the risk of atherosclerosis, organic and functional damage to the myocardium, and stroke.

The most safe and effective are statins under the names: Atorvastatin, Rosuvastatin, Simvastatin. You can also use their analogues.

The interaction of ethanol and lipid-lowering drugs is unpredictable, so there is no such information in the instructions for the pharmacy. But we can definitely say that these components cannot be compatible. Their simultaneous reception causes the following reactions:

1. Neutralization of the positive effect of a statin. Drug treatment during the period of binge will be completely depreciated.
2. Strengthening the effect of the drug. Lack of cholesterol in the body is also dangerous and can cause osteoporosis, obesity or infertility.
3. Intensive manifestations of side effects.

To lower the level of cholesterol in the body, it is recommended to follow a special diet in which alcohol is completely replaced by green tea. Some doctors allow you to drink 200 ml of dry red wine per day, but combining strong drinks with statins is contraindicated.

With dependence on alcohol, liver cells are gradually destroyed and replaced by connective tissue, bile stasis occurs. The compatibility of ethanol with medicines increases the load on the organ. The appearance of inflammatory processes and the gradual death of hepatocytes in the liver become almost inevitable.

Side effects and consequences

Alcohol enhances the side effects of the drug, so their combination can provoke a number of complications:

• irritability, lethargy, severe mood swings;
• sleep problems;
• nausea, vomiting;
• chills, convulsions;
• an increase in heart rate or a sharp drop in blood pressure;
• indigestion, diarrhea;
• skin rashes;
• an allergic reaction, which may result in anaphylactic shock or Quincke's edema;
• erectile dysfunction.

Alcohol abuse increases the risk of blood clots in the blood vessels. With concomitant atherosclerosis, statins may not have time to reduce the amount of cholesterol in the bloodstream. The consequences of such phenomena are often stroke, myocardial infarction and even death.

Scientists have also proven the adverse effects of statins on the kidneys. Like alcohol, lipid-lowering drugs cause a syndrome of violation of all organ functions. Therefore, with such a combination, the likelihood of renal failure and alcoholic nephropathy increases significantly.

Correct alignment

As an example, for combining alcoholic beverages and a statin, let's take the drug Rosuvastatin. The drug is completely contraindicated to be used simultaneously with alcoholic beverages, at all stages of pregnancy and during course treatment.

To avoid negative consequences, before drinking, you should not use the drug exactly one day for men, 32 hours for women. After drinking alcohol, it is necessary to maintain an interval of 14 hours for men and 20 hours for the fairer sex. After completing the treatment course, the doctor determines the possible intake of alcohol, usually the interval between the last dose of the statin used and alcohol consumption is from 3 days to 1 month (average 15 days).

If the instructions are not followed, stop drinking alcohol and drink as much water as possible in the next 4 hours. Otherwise, the risks of arrhythmias, acute heart failure, and orthostatic hypotension increase significantly.

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