Composition, form of production and packaging
The tablets covered with a film cover of yellow color, round, biconcave, with engraving "ZD4522 5" on one side.
1 tab.
rosuvastatin (in the form of rosuvastatin calcium) 5 mg
Excipients: lactose monohydrate - 93.08 mg, microcrystalline cellulose - 31.02 mg, calcium phosphate - 11.32 mg, crospovidone - 7.5 mg, magnesium stearate - 1.88 mg.
The composition of the film shell: lactose monohydrate - 1.8 mg, hypromellose - 1.26 mg, triacetin (glycerol trigate acetate) - 0.036 mg, titanium dioxide - 0.9 mg, iron oxide oxide yellow - 0.18 mg.
14 pcs. - blisters (2) - packs of cardboard.
The tablets covered with a film cover of pink color, round, biconcave, with engraving "ZD4522 10" on one side.
1 tab.
rosuvastatin (in the form of rosuvastatin calcium) 10 mg
Excipients: lactose monohydrate - 89.5 mg, microcrystalline cellulose - 29.82 mg, calcium phosphate - 10.9 mg, crospovidone - 7.5 mg, magnesium stearate - 1.88 mg.
The composition of the film shell: lactose monohydrate - 1.8 mg, hypromellose - 1.26 mg, triacetin (glycerin triacetate) - 0.36 mg, titanium dioxide - 1.06 mg, iron oxide red oxide - 0.02 mg.
7 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
The tablets covered with a film cover of pink color, round, biconcave, with engraving "ZD4522 20" on one side.
1 tab.
rosuvastatin (in the form of rosuvastatin calcium) 20 mg
Excipients: lactose monohydrate - 179 mg, microcrystalline cellulose - 59.64 mg, calcium phosphate - 21.8 mg, crospovidone - 15 mg, magnesium stearate - 3.76 mg.
The composition of the film shell: lactose monohydrate - 3.6 mg, hypromellose - 2.52 mg, triacetin (glycerin triacetate) - 0.72 mg, titanium dioxide - 2.11 mg, iron oxide red oxide - 0.05 mg.
14 pcs. - blisters (2) - packs of cardboard.
The tablets covered with a film cover of pink color, oval, biconcave, with engraving "ZD4522" on one side and "40" on the other.
1 tab.
rosuvastatin (in the form of rosuvastatin calcium) 40 mg
Excipients: lactose monohydrate - 164.72 mg, microcrystalline cellulose - 54.92 mg, calcium phosphate - 20 mg, crospovidone - 15 mg, magnesium stearate - 3.76 mg.
The composition of the film shell: lactose monohydrate - 3.6 mg, hypromellose - 2.52 mg, triacetin (glycerin triacetate) - 0.72 mg, titanium dioxide - 2.11 mg, iron oxide red oxide - 0.05 mg.
7 pcs. - blisters (4) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
A hypolipidemic drug, a selective competitive inhibitor of HMG-CoA reductase.
Crestor В® reduces elevated concentrations of LDL cholesterol (LDL-C), total cholesterol, triglycerides (TG), increases the concentration of high-density cholesterol-lipoproteins (HDL-C), and also reduces concentrations of apolipoprotein B (ApoV), CS-non-HDL, XC -LVPP, TG-VLDL and increases the concentration of apolipoprotein AI (ApoA-I) (see Tables 1 and 2), reduces the ratio of LDL-C, HDL-C, HDL-C and HDL-C-HDL-C and HDL-C the ratio of РђРїРѕР’ / РђРїРѕРђ-1.
Therapeutic effect develops within one week after the beginning of Krestor В® therapy, 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 intake of the drug.
Tables 1 and 1a show a dose-dependent effect in patients with primary hypercholesterolemia (type IIa and IIb according to Fredrickson) (mean adjusted percentage change compared to the baseline value).
Table 1
Dose Number of patients with LDL-C-cholesterol Total XC-HDL-C
Placebo 13 -7 -5 3
5 mg 17 -45 -33 13
10 mg 17 -52 -36 14
20 mg 17 -55 -40 8
40 mg 18 -63 -46 10
Table 1a
Dose Number of patients TG CS-non-HDL Apo In Apo AI
Placebo 13 -3 -7 -3 0
5 mg 17 -35 -44 -38 4
10 mg 17 -10 -48 -42 4
20 mg 17 -23 -51 -46 5
40 mg 18 -28 -60 -54 0
Tables 2 and 2a show a dose-dependent effect in patients with hypertriglyceridemia (type IIb and IV according to Fredrickson) (mean percentage change compared to the baseline value).
table 2
Dose Number of patients TG LDL-cholesterol Total XC-HDL-C
Placebo 26 1 5 1 -3
5 mg 25 -21 -28 -24 3
10 mg 23 -37 -45 -40 8
20 mg 27 -37 -31 -34 22
40 mg 25 -43 -43 -40 17
Table 2a
Dose Number of patients with HC-non-HDL- CS-VLDL TG-VLDLP
Placebo 26 2 2 6
5 mg 25 -29 -25 -24
10 mg 23 -49 -48 -39
20 mg 27 -43 -49 -40
40 mg 25 -51 -56 -48
Clinical efficacy
Crestor В® is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia; regardless of race, sex or age, incl. in patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with Fredrickson IIa and IIb type cholesterolinemia (mean baseline LDL-C concentration of about 4.8 mmol / L), when taking the drug at a dose of 10 mg, the concentration of LDL-C is lower than 3 mmol / l.
Patients with heterozygous familial hypercholesterolemia who receive Krestor В® at a dose of 20-80 mg show a positive dynamics of lipid profile (a study involving 435 patients). After titration to a daily dose of 40 mg (12 weeks of therapy), the concentration of LDL-C is decreased by 53%. In 33% of patients the concentration of LDL-C is less than 3 mmol / l.
In patients with homozygous familial hypercholesterolemia who take Crstor В® at a dose of 20 mg and 40 mg, the average decrease in the concentration of LDL-C is 22%. In patients with hypertriglyceridemia with an initial TG concentration of 273 to 817 mg / dl, who received CrestorВ® at a dose of 5 mg to 40 mg once daily for 6 weeks, the concentration of TG in plasma was significantly reduced (see Table 2). The additive effect is noted in combination with fenofibrate for the concentration of triglycerides and with nicotinic acid in lipid-lowering doses for the concentration of cholesterol-HDL.
In a METEOR study involving 984 patients aged 45-70 years with a low risk of developing CHD (a 10-year risk for the Framingham scale of less than 10%), an average LDL cholesterol concentration of 4.0 mmol / L (154.5 mg / dL) and subclinical atherosclerosis which was estimated by the thickness of the intima-media complex of carotid arteries (TKIM)), the influence of rosuvastatin on the thickness of the intima-media complex was studied. Patients received rosuvastatin 40 mg / day or placebo for 2 years. Rosuvastatin therapy significantly slowed the progression of the maximum TKIM for 12 segments of the carotid artery compared with placebo with a difference of -0.0145 mm / year [95% confidence interval from -0.0196 to -0.0093; p <0.001]. Compared with baseline values ​​in the rosuvastatin group, a decrease in the maximum TKIM value by 0.0014 mm / year (0.12% / year (unreliable difference)) was observed compared to an increase of 0.0131 mm / year (1.12% / year (p <0.001) ) in the placebo group. To date, there has been no direct correlation between a decrease in TKIM and a reduction in the risk of cardiovascular events. The METEOR trial was performed in patients with a low risk of coronary artery disease, for whom a dose of Krestor ® 40 mg is not recommended. A dose of 40 mg should be given to patients with severe hypercholesterolemia and a high risk of cardiovascular disease.
The results of the JUPITER study (Justification of the use of statins for primary prevention: an interventional study evaluating rosuvastatin) in 17802 patients showed that rosuvastatin significantly reduced the risk of cardiovascular complications (252 in the placebo group compared to 142 in the rosuvastatin group) (p <0.001 ) with a relative risk reduction of 44%. The effectiveness of therapy, was noted in the first 6 months of the drug. A statistically significant 48% reduction in the combined test, including death from cardiovascular causes, stroke and myocardial infarction (risk ratio 0.52, 95% confidence interval 0.40-0.68, p <0.001), a 54% decrease in the incidence of fatal or nonfatal myocardial infarction (risk ratio: 0.46, 95%, confidence interval 0.30-0.70) and 48% - fatal or nonfatal stroke. Overall mortality decreased by 20% in the rosuvastatin group (risk ratio: 0.80, 95%, confidence interval 0.67-0.97, p = 0.02). The safety profile of patients taking rosuvastatin at a dose of 20 mg was generally similar to the safety profile in the placebo group.
PHARMACOKINETICS
Suction and distribution
C max rosuvastatin in blood plasma is reached approximately 5 hours after ingestion. Absolute bioavailability is approximately 20%.
Rosuvastatin is metabolized primarily by the liver, which is the main site for the synthesis of cholesterol and the metabolism of LDL-C. V d of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to blood plasma proteins, mainly albumin.
Metabolism
It is subject to limited metabolism (about 10%). Rosuvastatin is a non-core substrate for metabolism by enzymes of the cytochrome P450 system. The main isoenzyme involved in the metabolism of rosuvastatin is the isoenzyme CYP2C9. Isozymes CYP2C19, CYP3A4 and CYP2D6 are less involved in metabolism.
The main revealed metabolites of rosuvastatin are N-desmethyl-rosuvastatin and lactone metabolites. N-desmethylrosuvastatin is approximately 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 - by its metabolites.
Excretion
About 90% of the dose of rosuvastatin is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin). The rest is excreted by the kidneys. Plasma T 1/2 is approximately 19 hours. T 1/2 does not change with increasing dose of the drug. The average geometric plasma clearance is approximately 50 l / h (coefficient of variation of 21.7%). As in the case of other HMG-CoA reductase inhibitors, a membrane cholesterol transporter involved in the hepatic elimination of rosuvastatin plays an important role in the hepatic elimination of rosuvastatin.
Linearity
The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily intake.
Pharmacokinetics in special clinical cases
Age and gender do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.
Ethnic groups. Pharmacokinetic studies showed approximately a twofold increase in the median AUC and C max of rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with Caucasians; Indians showed an increase in the median AUC and C max by 1.3 times.Pharmacokinetic analysis did not reveal clinically significant differences in pharmacokinetics among Caucasians and representatives of the Negroid race.
Renal failure. In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethyl-rosuvastatin does not change significantly. In patients with severe renal failure (CC less than 30 ml / min), the concentration of rosuvastatin in the blood plasma is 3 times higher, and the concentration of N-desmethyl-rosuvastatin is 9 times higher than in healthy volunteers. The concentration of rosuvastatin in blood plasma in patients on hemodialysis was approximately 50% higher than in healthy volunteers.
Liver failure. Patients with different stages of hepatic insufficiency did not have an increase in T 1/2 of rosuvastatin in patients with 7 points or lower on the Child-Pugh scale. Two patients with 8 and 9 points on the Child-Pugh scale had an increase in T 1/2 , at least 2-fold. The experience with rosuvastatin in patients with more than 9 points on the Child-Pugh scale is not available.
INDICATIONS
- Fredrickson's primary hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet, when diet and other non-medicamentous treatments (eg, exercise, weight loss) are insufficient;
- family homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (eg, LDL-apheresis), or in cases where such therapy is not effective enough;
- 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 are 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 IHD, but with an increased risk of its development (age over 50 for men and over 60 for women, increased concentration of C-reactive protein (? 2 mg / L) in the presence of at least one of additional risk factors, such as hypertension, low concentration of HDL-C, smoking, family history of early onset of CHD).
DOSING MODE
Inside, do not chew and do not grind the tablet, swallow whole, squeezed water. The drug can be administered at any time of the day, regardless of food intake. Before starting therapy with Krestor В®, the patient should begin to follow the standard hypocholesterolemic diet and continue to observe it during treatment. The dose of the drug should be selected individually, depending on the purpose of therapy and the therapeutic response to treatment, taking into account the current recommendations for target lipid concentrations.
The recommended initial dose for patients starting to take the drug, or for patients transferred from other HMG-CoA reductase inhibitors, should be 5 or 10 mg of Crestor В® 1 time / day. When choosing an initial dose, individual cholesterol concentration should be guided and the possible risk of cardiovascular complications should be taken into account, and the potential risk of side effects should be assessed. If necessary, the dose may be increased to greater after 4 weeks.
In connection with the possible development of side effects when taken in a dose of 40 mg, compared with lower doses of the drug, an increase in the dose of up to 40 mg after additional doses above the recommended initial dose for 4 weeks of therapy can be performed only in patients with a severe degree hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who did not achieve the desired result of therapy when taking a dose of 20 mg and which will be monitored by the sp cialist. It is recommended especially careful monitoring of patients receiving the drug in a dose of 40 mg.
It is not recommended to administer 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 the drug Krestor В®, it is necessary to monitor the lipid metabolism (if necessary, dose adjustment is required).
Older patients do not need a dose adjustment.
In patients with mild or moderate renal insufficiency, dose adjustment is not required. In patients with severe renal insufficiency (KC less than 30 ml / min), theuse of the drug Crestor В® is contraindicated. Contraindicated use of the drug in a dose of 40 mg in patients with moderate renal dysfunction (KK 30-60 ml / min).Patients with moderate impairment of renal function are recommended an initial dose of 5 mg.
Patients with hepatic impairment: Crestor В® is contraindicated in patients with liver disease in the active phase.
Ethnic groups. When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, there was an increase in the systemic concentration of rosuvastatin among Japanese and Chinese. This fact should be taken into account when prescribing Crestor В® to these patient groups. When appointing doses of 10 and 20 mg, the recommended initial dose for patients of the Mongoloid race is 5 mg. Contraindicated the appointment of the drug in a dose of 40 mg to patients of the Mongoloid race.
Patients who are predisposed to myopathy. Contraindicated the appointment of the drug in a dose of 40 mg to patients with factors that may indicate a predisposition to the development of myopathy. When appointing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg.
SIDE EFFECT
Side effects observed with the use of the drug Crestor В® , usually expressed slightly and pass independently. As with other inhibitors of HMG-CoA reductase, the incidence of side effects is mainly dose-dependent.
Determination of the incidence of adverse reactions: often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10 000, <1/1000); very rarely (<1/10 000), including individual messages.
From the immune system: rarely - reactions of hypersensitivity, including angioedema.
On the part of the endocrine system: often - type 2 diabetes.
From the side of the central nervous system: often - headache, dizziness.
From the digestive system: often - constipation, nausea, abdominal pain; rarely - pancreatitis.
From the skin: rarely - skin itching, rash, urticaria.
From the osteomuscular system: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis.
From the side of the urinary system: in patients receiving Crestor В® , proteinuria can be detected. Changes in the amount of protein in the urine (from absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving the drug at a dose of 10-20 mg and about 3% of patients receiving the drug at a dose of 40 mg. A slight change in the amount of protein in urine observed when receiving a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not imply the occurrence of acute or progression of existing kidney disease.
From the musculoskeletal system: when using the drug Crestor В® at all doses, particularly at doses of over 20 mg - myalgia, myopathy (including myositis); in rare cases - rhabdomyolysis with acute renal failure or without her.
A dose-related increase in CK levels observed in a small number of patients taking rosuvastatin. In most cases, it was small, asymptomatic and transient. In case of increase of CPK activity (more than 5 times compared to the ULN) therapy should be suspended.
Liver: dose-dependent increases in liver transaminases in a small number of patients. In most cases, it is insignificant, symptoms temporarily.
Laboratory indicators: increase in the concentration of glucose, bilirubin, GGT activity of alkaline phosphatase, thyroid dysfunction.
Other: often - asthenic syndrome.
Post-marketing use of
part of the digestive system: very rarely - jaundice, hepatitis; rarely - increased activity of hepatic transaminases; unspecified frequency - diarrhea.
On the part of the musculoskeletal system: very rarely - arthralgia; unspecified frequency - immune-mediated necrotizing myopathy.
CNS:very rarely - polyneuropathy, memory loss.
The respiratory system: not specified frequency - cough, shortness of breath.
From the urinary system: very rarely - hematuria.
For the skin and subcutaneous fat: unspecified frequency - Stevens-Johnson syndrome.
Reproductive system: unspecified frequency - gynecomastia.
Other: unspecified frequency - peripheral edema.
With some statins reported the following side effects: depression, sleep disorders, including insomnia and nightmares, sexual dysfunction. It reported a few cases of interstitial lung disease, especially with prolonged use of drugs.
CONTRAINDICATIONS
For preparation Crestor В® in a daily dose of 5 mg, 10 mg and 20 mg:
- hypersensitivity to rosuvastatin or any of the components;
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (formulation contains lactose);
- children and adolescence under 18;
- liver disease in its active phase, including persistent elevation of serum transaminases and any increase in transaminase activity in serum (more than 3 times compared to the ULN);
- pronounced renal dysfunction (creatinine clearance less than 30 mL / min);
- myopathy;
- concomitant use of cyclosporine;
- women: pregnancy, lactation, lack of adequate contraceptive methods;
- patients with a predisposition to the development of miotoksicheskih complications.
For preparation Crestor В® in a daily dose of 40 mg:
- hypersensitivity to rosuvastatin or any of the components;
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (formulation contains lactose);
- children and adolescence under 18;
- concomitant use of cyclosporine;
- women: pregnancy, lactation, lack of adequate contraceptive methods;
- liver disease in its active phase, including persistent elevation of serum transaminases and any increase in transaminase activity in serum (more than 3 times compared to the ULN);
- patients with risk factors for myopathy / rhabdomyolysis, namely, renal insufficiency moderate severity (KKmenee 60 ml / min), hypothyroidism, personal or family history of muscle diseases miotoksichnost in patients receiving other HMG-CoA reductase inhibitors or fibrates history ;
- excessive use of alcohol;
- conditions that may lead to increased plasma concentrations of rosuvastatin;
- concomitant use of fibrates;
- patients of the Mongoloid race.
With caution
for the preparation Crestor В® in a daily dose of 5 mg, 10 mg and 20 mg: there is a risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, personal or family history of hereditary muscular disease and the previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; age over 65 years; conditions in which marked increase in plasma concentrations of rosuvastatin; race (Mongoloid race); co-administration with fibrates; a history of liver disease; sepsis; arterial hypotension; extensive surgery, trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures.
For preparation Crestor В® in a daily dose of 40 mg: renal failure mild severity (CC 60 ml / min); age over 65 years; a history of liver disease; sepsis; arterial hypotension; extensive surgery, trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures.
Data or experience with the drug in patients with hepatic insufficiency and with more than 9 points on a scale Child-Pugh is absent.
PREGNANCY AND LACTATION
Crestor В® is contraindicated in pregnancy and lactation (breast feeding).
Women of childbearing age should use adequate contraception.
Since cholesterol and other products of cholesterol biosynthesis are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase inhibitors outweigh the benefits of the drug in pregnant women.
In case of pregnancy during therapy the drug should be discontinued immediately.
Data on the allocation of rosuvastatin with breast milk are not available, so the breastfeeding period, the drug should be discontinued
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with renal insufficiency mild or moderate dose adjustment is required. In patients with severe renal failure (creatinine clearance less than 30 mL / min) using the product Crestor В® is contraindicated. Do not use this drug in the dose of 40 mg in patients with moderate renal impairment (creatinine clearance of 30-60 ml / min).
Patients with moderate renal impairment recommended initial dose of 5 mg.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Crestor is contraindicated in patients with liver disease in active phase.
APPLICATION IN ELDERLY PATIENTS
It does not require dose adjustment. Caution should be exercised.
SPECIAL INSTRUCTIONS
Effect on kidney
in patients receiving high doses of the drug Crestor В® (generally 40 mg) tubular proteinuria was observed that, in most cases, was transient. This showed no proteinuria of renal disease or acute renal disease progression. Patients taking the drug at a dose of 40 mg is recommended to monitor renal function during treatment.
From the musculoskeletal
In applying the drug Crestor В® at all doses, particularly at doses of over 20 mg, reported the following effects on the musculoskeletal system: myalgia, myopathy, in rare cases - rhabdomyolysis.
Determination of CK
Determination of CK levels should not be carried out after intense exercise or when there are other possible reasons for the increased CPK, which can lead to misinterpretation of the results. If the source CK levels significantly increased (above 5 times ULN), after 5-7 days should conduct measurement again. Should not begin therapy if retest confirms the initial CK activity (higher by more than 5 times compared to the ULN).
Prior to initiation of therapy
When assigning drug Crestor В® , as well as the appointment other inhibitors of HMG-CoA reductase, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis, we must consider the ratio of risk and potential benefit of therapy and to carry out clinical observation.
During therapy
should inform the patient about the need for immediate communication to the doctor about the sudden appearance of cases of muscle pain, muscle weakness or cramps, particularly in combination with malaise and fever. Such patients should be to determine the activity of CK. Therapy should be discontinued if CK activity increased significantly (by more than 5 times in comparison with the UNL) or if the part of the muscle symptoms are pronounced and cause daily discomfort (even if CK activity is 5 times less than the ULN).
If the symptoms disappear, and the activity of CK returns to normal, you should consider re-appointment of the drug Crestor В® or other inhibitors of HMG-CoA reductase in smaller doses with careful observation of the patient.
Routine control CPK activity in the absence of symptoms impractical. Very rare cases of immune-mediated necrotising myopathy with clinical manifestations of a reception proximal muscle weakness and increase in serum CPK levels during treatment or discontinuation of statins, including rosuvastatin. You may need to conduct additional studies of the musculoskeletal system and the nervous system, serology, and immunosuppressive agents therapy.
There was no evidence of increased impact on skeletal muscle when taking the drug Crestor В®and concomitant therapy. However, increasing the number of reported cases of myositis and myopathy in patients taking other inhibitors of HMG-CoA reductase inhibitor in combination with a fibric acid derivatives including gemfibrozil, cyclosporin, nicotinic acid, azole antifungal agents, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with some HMG-CoA reductase. Thus, without the simultaneous application of the drug Crestor В® and gemfibrozil. One should carefully weigh ratio of risk and potential benefit in the combined use of the drug Crestor В® and fibrates or lipid-lowering doses of nicotinic acid. Medication contraindicated reception Crestor В®40mg conjunction with fibrates. After 2-4 weeks of treatment and / or by increasing the dose Crestor В® requires control lipid metabolism (dose required correction if necessary).
The liver
is recommended that the definition of indicators of liver function before treatment and at 3 months after initiation of therapy. Receiving drug Crestor В® discontinue or decrease the dose when transaminase activity in serum: 3 times the ULN.
In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, major disease therapy should be conducted prior to drug treatment Crestor В® .
Special populations: ethnic groups
During pharmacokinetic studies among Chinese and Japanese patients showed an increase in systemic concentrations of rosuvastatin compared with those obtained in patients - Caucasians.
HIV protease inhibitors
is not recommended since the combined use of the preparation of HIV protease inhibitors.
Lactose
drug should not be used in patients with lactase insufficiency, intolerance to galactose and glucose-galactose malabsorption.
Interstitial lung disease
With some statins especially for a long time been reported a few cases of interstitial lung disease. Manifestations of the disease may include dyspnea, nonproductive cough and worsening of general condition (weakness, weight loss and fever). For suspected interstitial lung disease should be discontinued statin therapy.
Type 2 diabetes
patients with a glucose concentration of from 5.6 to 6.9 mmol / l of drug therapy Crestor В® associated with increased risk of type 2 diabetes.
Impact on the ability to drive vehicles and manage mechanisms
No studies on the effect of the drug Crestor В® on the ability to drive and use machinery. Caution must be exercised when driving or work requiring high concentration and psychomotor speed reactions (during therapy dizziness can occur).
OVERDOSE
At simultaneous reception of several daily doses of rosuvastatin pharmacokinetic parameters are not changed.
Specific treatment of overdosage with rosuvastatin does not exist. In case of overdose symptomatic treatment is recommended and measures aimed at maintaining the functions of the vital organs and systems. Necessary to monitor liver function and CK levels. It is unlikely that dialysis would be effective.
DRUG INTERACTION
Cyclosporin: while applying rosuvastatin and cyclosporine rosuvastatin AUC was on average 7-fold higher than the value which was seen in healthy volunteers. The combined use of rosuvastatin increases the plasma concentration of blood 11 times. No effect on the plasma concentration of cyclosporine.
Indirect anticoagulants: initiation of therapy rosuvastatin or increasing doses in patients receiving simultaneously indirect anticoagulants (eg, warfarin), may lead to an increase in the prothrombin time (MHO). Cancel rosuvastatin, or reduction in dose may result in a reduction MHO. In such cases, control MHO.
Gemfibrozil and other lipid-lowering agents:the combined use of gemfibrozil and rosuvastatin leads to an increase in 2 times C max rosuvastatin plasma AUC and rosuvastatin. Based on data on the specific interaction is not expected significant pharmacokinetic interactions with fenofibrate possible pharmacodynamic interactions.
Gemfibrozil, fenofibrate, fibrates and other lipid-lowering doses of nicotinic acid have increased risk of myopathy with the simultaneous use of inhibitors of HMG-CoA reductase, possibly due to the fact that they can cause myopathy and when used as monotherapy. When simultaneous administration of the drug with gsmfibrozilom, fibrates, nicotinic acid, in a dose of 1 g / day to patients recommended initial dose of 5 mg.
ezetimibe:simultaneous application of the drug Crestor В® and ezetimibe was not accompanied by a change in AUC and C max of both drugs.
HIV protease inhibitors: although the exact mechanism of the interaction is unknown, co-administration of HIV protease inhibitors, may lead to significantly increase the
