Ezetrol - instructions for use, dose, side effects, contraindications

Active substanceEzetimibeEzetimibe

Similar drugsTo uncover

Lipbon®

pills inwards

EGIS ZAO Pharmaceutical Plant Hungary

Ezetrol®

pills inwards

Schering-Plau N. Labo. Belgium

Dosage form: & nbsppills

Composition:

Each tablet contains the active substance ezetimibe - 10 mg.

Excipients: lactose monohydrate 55 mg, microcrystalline cellulose 20 mg, povidone (K29-32) 4 mg, croscarmellose sodium 8 mg, sodium lauryl sulfate 2 mg, magnesium stearate 1 mg.

Description:

Tablets of capsular form from white to almost white with an engraving "414" on one side.

Pharmacotherapeutic group:lipid-lowering agent - cholesterol absorption inhibitor

ATX: & nbsp

C.10.A.X.09 Ezetimibe

Pharmacodynamics:

Ezetimibe is the representative of a new class of lipid-lowering agents that selectively inhibit the absorption of cholesterol (cholesterol) and certain plant sterols in the intestine.

Ezetrol is effective when taken orally. The mechanism of action of ezetimibe differs from the mechanism of action of other classes of lipid-lowering agents (for example, inhibitors of HMG-CoA reductase (statins), bile acid sequestrants, fibrates and plant stanols). The molecular target of ezetimibe is transport protein (Niemann-Pick Cl-Like 1, NPC1L1), responsible for absorption in the intestines of cholesterol and phytosterols.

Ezetimibe is localized in the brush border of the small intestine and prevents absorption of cholesterol, leading to a decrease in the intake of cholesterol from the intestine into the liver, thereby reducing the cholesterol levels in the liver and increasing the excretion of cholesterol from the blood. Ezetimibe does not enhance the excretion of bile acids (as opposed to bile acid sequestrants) and does not inhibit the synthesis of cholesterol in the liver (as opposed to statins).

In a 2-week clinical trial in which 18 patients with hypercholesterolemia were included, Ezetrol® reduced the absorption of cholesterol in the intestine by 54% compared with placebo. Inhibiting the absorption of cholesterol in the intestine, ezetimibe reduces the intake of cholesterol into the liver. Statins reduce the synthesis of cholesterol in the liver. With simultaneous use, the preparations of these two groups provide an additional reduction in the concentration of cholesterol. Ezetrol®, taken concomitantly with statins, reduces the concentration of total cholesterol (LDL), low density lipoprotein cholesterol (LDLP), apolipoprotein B (apo-B), low-density lipoprotein cholesterol (non-HDL cholesterol, calculated as the difference between the concentration of OXC and concentration of HDL cholesterol) and triglycerides (TG),and also increases the concentration of high density lipoprotein cholesterol (HDL cholesterol) in blood plasma in patients with hypercholesterolemia to a greater extent than ezetimibe or statin, taken in monotherapy. The simultaneous use of Ezetrol® with fenofibrate reduces the concentration of cholesterol, LDL-C, AP-B, TG, and non-HDL cholesterol, and also increases the concentration of HDL cholesterol in plasma in patients with mixed hypercholesterolemia.

Clinical studies have shown that elevated concentrations of OXC, LDL cholesterol and apo-B (the main protein component of LDL) contribute to the development of atherosclerosis.

In addition, a reduced concentration of CMLP is also associated with the development of atherosclerosis. The results of epidemiological studies have shown that cardiovascular morbidity and mortality are directly related to concentrations of OXC and LDL cholesterol and in inverse relationship to the concentration of HDL cholesterol.

Like LDL, lipoproteins, rich in cholesterol and TG, including very low-density lipoproteins (VLDL), intermediate-density lipoproteins (ALTs) and remnants, can also contribute to the development of atherosclerosis.

To determine the selectivity of ezetimibe against inhibition of suction of cholesterol, a series of preclinical studies was performed. Ezetimibe inhibited absorption [¹⁴C] -cholesterol and did not affect the absorption of TG, fatty acids, bile acids, progesterone, ethinyl estradiol or fat-soluble vitamins A and D.

Pharmacokinetics:

Suction

After oral administration ezetimibe rapidly absorbed and extensively metabolized in the small intestine and liver by conjugation to pharmacologically active phenolic glucuronide (ezetimibe-glucuronide). The maximum concentration in the blood plasma (Cmax) of ezetimibe-glucuronide is observed after 1-2 hours, ezetimibe in 4-12 hours. The absolute bioavailability of ezetimibe can not be determined, since this substance is practically insoluble in none of the aqueous solvents used for the preparation of injectable solutions.

Food intake (low or high fat) did not affect the bioavailability of ezetimibe when ingesting Ezetrol® in the form of 10 mg tablets. The drug Ezetrol® can be taken regardless of food intake.

Distribution

Ezetimibe and ezetimibe-glucuronide bind to plasma proteins at 99,7% and 88%92% respectively.

Metabolism

Metabolism of ezetimibe occurs mainly in the small intestine and liver by conjugation with glucuronide (phase II reaction), followed by excretion with bile. Ezetimibe is minimally exposed to oxidative metabolism (I phase reaction).

Ezetimibe and ezetimibe-glucuronide (ezetimibe basic derivatives defined in blood plasma) is 10-20% and 80-90% respectively of the total ezetimibe concentration in blood plasma. Ezetimibe and ezetimibe-glucuronide are slowly removed from the blood plasma during intestinal hepatic recirculation. The half-life for ezetimibe and ezetimibe-glucuronide is approximately 22 hours.

Excretion

After ingestion of 20 mg of ezetimibe labeled ¹⁴C, 93% of total ezetimibe was detected in the blood plasma (ezetimibe + ezetimib-glucuronide) from the total level of radioactive products. Within 10 days, approximately 78% of the radioactive products taken were excreted through the intestines with bile, 11% through the kidneys. After 48 hours no radioactive products were detected in the blood plasma.

Pharmacokinetics in special patient groups Children and adolescents

The pharmacokinetic parameters of ezetimibe were similar in children older than 6 years and adults. Pharmacokinetic data for children younger than 6 years are absent.

Elderly patients

In elderly patients (over 65 years of age), the total ezetimibe concentration in the blood plasma is approximately 2 times higher than in younger patients (18 to 45 years). The degree of decrease in LDL cholesterol concentration and the safety profile were comparable in elderly and younger patients taking Ezetrol®. For elderly patients, no dose selection is required.

Patients with hepatic insufficiency

After a single dose of 10 mg ezetimibe, the mean area under the concentration-time curve (AUC) of total ezetimibe was 1.7 times greater in patients with mild liver failure (5-6 on the Child-Pugh scale) than in healthy volunteers. In a 14-day study using ezetimibe at a dose of 10 mg / day with patients with moderate degrees of hepatic insufficiency (7-9 on the Child-Pugh scale), the mean AUC of total ezetimibe increased 4-fold on days 1 and 14 compared with healthy volunteers.For patients with mild hepatic insufficiency, dose adjustment is not required. Since the effects of increasing the AUC value of total ezetimibe are unknown, ezetimibe It is not recommended for patients with moderate and severe degree (more than 9 on the Child-Pugh scale) of liver failure (see Cautiousness).

Patients with renal insufficiency

After a single administration of ezetimibe at a dose of 10 mg in patients with severe impairment

renal function (n = 8, creatinine clearance (CK) not more than 30 ml / min / 1.73 m), the AUC value of total ezetimibe increased approximately 1.5 times in comparison with healthy volunteers (n = 9). This result is not clinically relevant. For patients with impaired renal function, no dose selection is required.

The patient after kidney transplantation received complex therapy, including ciclosporin, value AUC the total ezetimibe increased 12-fold.

Floor

The concentration of total ezetimibe in the blood plasma is slightly higher in women (less than 20%) than in men. The degree of decrease in LDL cholesterol and the safety profile are the same for men and women who take ezetimibe. Therefore, for patients male or female, no dose selection is required.

Indications:

Primary hypercholesterolemia

The preparation Ezetrol® in combination with inhibitors of HMG-CoA reductase (statins) or in monotherapy in addition to diet is indicated to reduce elevated concentrations of OXC, LDL cholesterol, apo-B, TG and cholesterol non-HDL cholesterol, and also to increase HDL cholesterol in patients with primary (heterozygous familial and non-family) hypercholesterolemia.

The drug Ezetrol® in combination with fenofibrate in addition to diet is indicated to reduce the elevated concentrations of OXC, LDL cholesterol, apo-B, and cholesterol non-HDL in patients with mixed hypercholesterolemia (see DOSAGE AND ADMINISTRATION).

Homozygous familial hypercholesterolemia

Ezetrol® in combination with statin is indicated to reduce the elevated concentrations of OXC and LDL cholesterol in patients with homozygous familial hypercholesterolemia. Patients may also receive supportive treatment (eg, LDL-apheresis).

Homozygous sitosterolemia (phytosterolemia)

Ezetrol® is indicated to reduce the increased concentration of sitosterol and campesterol in patients with homozygous familial sitosterolemia

Contraindications:

- Hypersensitivity to any of the components of the drug.

- When prescribing Ezetrol® concomitantly with statin or fenofibrate to monitor contraindications, instructions for the use of additionally prescribed drugs should be followed.

- Ezetrol® is not recommended for patients with moderate to severe hepatic impairment (7-9 or more on the Child-Pugh scale, PHARMACOLOGICAL PROPERTIES, Pharmacokinetics in specific patient groups; METHOD OF APPLICATION AND DOSES).

- Children under 18 years.

- Lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

Caution should be exercised while using Ezetrol® with fibrates, cyclosporine and indirect anticoagulants (including warfarin and fluindione). Patients concurrently taking Ezetrol® and fenofibrate, should be aware of the possible risk of gallbladder disease.

Pregnancy and lactation:

Studies on animals with the introduction of ezetimibe did not reveal any direct or indirect

adverse effects on pregnancy, embryo / fetus development, childbirth and

postnatal development. When pregnant rats are administered ezetimibe in combination with

lovastatin, simvastatin, pravastatin or atorvastatin teratogenic effects were not observed. With the introduction of pregnant rabbits with a small frequency, defects in the development of the skeleton in the fetus were observed.

There are no clinical data on the use of Ezetrol® in pregnancy, so caution should be exercised when prescribing to pregnant women. In case of pregnancy, the use of Ezetrol® should be discontinued.

With the simultaneous use of Ezetrol® and statin, instructions for the use of this statin should be followed.

In studies on rats, it was found that ezetimibe is excreted with milk. There are no data on the isolation of ezetimibe with breast milk in women. Therefore, Ezetrol® should not be used during breastfeeding, if the potential benefit does not exceed the potential risk for the child. If the drug is necessary, the patient should stop breastfeeding.

Dosing and Administration:

Before starting treatment, patients should switch to the appropriate lipid-lowering diet and continue to follow this diet during the entire period of therapy with Ezetrol®

The drug is taken orally at any time of the day, regardless of food intake.

The dose of Ezetrol® with monotherapy or in combination with statin or fenofibrate is 10 mg once a day. The dose of fenofibrate should not exceed 160 mg once a day with simultaneous use with Ezetrol®.

Application in elderly patients

For elderly patients no dose selection is required (see PHARMACOLOGICAL PROPERTIES, Pharmacokinetics in special groups of patients).

Use in patients with hepatic impairment

For patients with mild degree of hepatic insufficiency (5-6 points on the Child-Pugh scale), a dose selection is not required. The use of Ezetrol® is not recommended for patients with moderate (7-9 points on the Child-Pugh scale) and severe (more than 9 on the Child-Pugh scale) impaired liver function (see PHARMACOLOGICAL PROPERTIES, Pharmacokinetics in special groups of patients; CONTRAINDICATIONS)

Use in patients with renal insufficiency

Monotherapy

For patients with impaired renal function, the dose of the drug is not required (see PHARMACOLOGICAL PROPERTIES, Pharmacokinetics in special groups of patients). Combination therapy with simvastatin

For patients with mild renal impairment (glomerular filtration rate (GFR) of at least 60 mL / min / 1.73 m2), the dose of Ezetrol® or simvastatin is not required. Patients with impaired renal function and GFR less than 60 mL / min / 1.73 m2 Ezetrol® is prescribed at a dose of 10 mg and simvastatin in a dose of 20 mg once a day in the evening. In these patients, the use of simvastatin in a higher dose should be carefully monitored.

With combined therapy with bile acid sequestrants

Ezetrol® should be taken at a dose of 10 mg once a day at least 2 hours before or 4 hours after taking bile acid sequestrants

Side effects:

In clinical studies of up to 112 weeks in which patients took Ezetrol® at a dose of 10 mg per day in monotherapy (n = 2,396), concomitantly with statin (n = 11,308) or concomitantly with fenofibrate (n = 185), the drug Ezetrol® showed good tolerability.Undesirable reactions were usually mild and transient; the overall incidence of adverse events and the frequency of discontinuation due to adverse effects with Ezetrol® were comparable to those seen with placebo.

The following frequent (> or = 1/100 and <1/10) or infrequent (> or = 1/1000 and <1/100) adverse reactions were observed with the use of Ezetrol® in monotherapy (n = 2396) at a frequency exceeding the same frequency when taking placebo (n = 1159), or with concomitant use of Ezetrol® with statin (n = 11308) at a frequency exceeding the same frequency when taking a statin in monotherapy (n = 9361).

When taking Ezetrol® in monotherapy Disorders from the metabolism and nutrition

Infrequent: decreased appetite.

Vascular disorders

Infrequent: "hot flashes" of blood to the skin of the face, increased blood pressure.

Disturbances from the respiratory system, chest and mediastinal organs Infrequent: cough.

Disorders from the gastrointestinal tract Frequent: abdominal pain, diarrhea, flatulence.

Infrequent: indigestion, gastroesophageal reflux, nausea.

Disturbances from musculoskeletal and connective tissue Infrequent: arthralgia, muscle spasms, pain in the neck.

General disorders
Frequent: fatigue.

Infrequent: chest pain, pain.

Laboratory and instrumental data

Infrequent: rise activity alanine aminotransferase (ALT) and / or aspartate aminotransferase (ACT), increased serum creatinine phosphokinase (CKF) activity, increased gamma-glutamyl transferase activity, and impaired hepatic function.

When taking Ezetrol® simultaneously with statin

Disturbances from the nervous system Frequent: headache.

Infrequent: paresthesia.

Disorders from the gastrointestinal tract Infrequent: dryness of the oral mucosa, gastritis.

Disturbances from the skin and subcutaneous tissues Infrequent: itchy skin, skin rash, urticaria.

Disturbances from musculoskeletal and connective tissue Frequent: myalgia.

Infrequent: back pain, muscle weakness, pain in the limb.

General disorders

Infrequent: asthenia, peripheral edema.

Laboratory and instrumental data

Frequent: increased ALT activity and / or ACT.

When taking Ezetrol® simultaneously with fenofibrate

Disorders from the gastrointestinal tract

Frequent: pain in the abdomen.

In a multicenter, double-blind clinical trial, for up to 1 year in patients with mixed hyperlipidemia incidence of clinically significant increasing (more than 3 times the upper limit of normal (ULN)) activity "liver" transaminase serum was 4.5% in the group of patients treated with fenofibrate in monotherapy, and 2.7% in the group of patients taking Ezetrol at the same time as fenofibrate. The frequency of cholecystectomy was 0.6% in the group of patients taking fenofibrate monotherapy and 1.7% in patients treated simultaneously with Ezetrol® drug fenofibrate (see. SPECIFIC NOTES). There was no increase in CKK activity (more than 10 times higher than UGN) in none of the treatment groups in this study.

Patients with chronic kidney disease

In a clinical study SHARP (Study cardio- and nephroprotective action) involving 4650 patients taking hypolipidemic drug combination with fixed doses of ezetimibe (10 mg) and simvastatin (20 mg), 1 times a day, and 4,620 patients receiving placebo, safety profiles were comparable throughout the observation period (median follow-up was 4.9 years).In this clinical study, only serious adverse events and discontinuation of the drug were recorded because of the development of adverse events. The frequency of discontinuation was comparable in both groups (10.4% in the group taking the fixed-dose combination drug ezetimibe and simvastatin, and 9.8% in the placebo group). The incidence of myopathy / rhabdomyolysis was 0.2% in the group of patients taking the fixed-dose combination drug ezetimibe and simvastatin, and 0.1% in the placebo group. A gradual increase in the activity of "hepatic" transaminases (more than 3 times higher than ULN) was observed in 0.7% of patients taking a combination drug with fixed doses of ezetimibe and simvastatin, and in 0.6% of patients taking placebo. In this clinical study, there was no statistically significant increase in the incidence of such adverse events as malignant neoplasms (9.4% in the group of patients taking the fixed-dose combination drug ezetimibe and simvastatin, and 9.5%taking placebo), hepatitis, cholecystectomy or complications of cholelithiasis or pancreatitis.

Laboratory indicators

In controlled clinical trials, the incidence of a clinically significant increase in the activity of "hepatic" transaminases in serum (ALT activity and / or ACT 3 or more times higher than IGN) was comparable with Ezetrol® in monotherapy (0.5%) and placebo (0.3%). When studying safety of combination therapy, the frequency of clinically significant increase in activity of "hepatic" transaminases in serum was 1.3% who took the drug Ezetrol® concomitantly with statin, and 0.4% in patients taking statin in monotherapy. The increase in serum transaminase activity was usually asymptomatic, was not accompanied by the development of cholestasis and passed both during the continuation of treatment and after the drug was discontinued.

The incidence of a clinically significant increase in CKK activity (10 or more times higher than ULN) in patients taking Ezetrol® in monotherapy was similar to that in patients taking placebo or statin in monotherapy.

Post-registration application experience

With the use of Ezetrol® during the post-marketing period, the following adverse reactions were reported without a causal link Violations from the blood and lymphatic system: thrombocytopenia.

Immune system disorders: hypersensitivity reactions, including anaphylaxis, angioedema, skin rash and hives.

Disorders from the psyche: depression.

Impaired nervous system: dizziness, paresthesia.

Disorders from the digestive system: pancreatitis, constipation.

Disorders from the liver and bile ducts: hepatitis, cholelithiasis, cholecystitis.

Disturbances from the skin and subcutaneous tissues: erythema multiforme.

Disturbances from the musculoskeletal and connective tissue: myalgia, myopathy / rhabdomyolysis (see SPECIAL INSTRUCTIONS).

General disorders: asthenia.

Overdose:

Several cases of overdose have been reported, most of which have not been associated with the occurrence of adverse events, and in the event of their occurrence, adverse events have not been serious.

In clinical trials in which ezetimibe was prescribed to 15 healthy volunteers at a dose of 50 mg per day for 14 days, to 18 patients with primary hypercholesterolemia in a dose of 40 mg per day for 56 days, or 27 patients with homozygous sitosterolemia at a dose of 40 mg per day for 26 weeks, a good tolerability of the drug was demonstrated.

In case of an overdose, symptomatic treatment and maintenance therapy should be performed.

Interaction:

In preclinical studies it was shown that ezetimibe does not induce cytochrome P450 isoenzymes involved in the metabolism of drugs. There was no clinically significant pharmacokinetic interaction between ezetimibe and agents metabolized by isoenzymes 1A2, 2D6, 2C8, 2C9 and 3A4 cytochrome P450 or N-acetyltransferase.

With simultaneous application ezetimibe does not affect the pharmacokinetics of dapsone, dextromethorphan, digoxin, oral contraceptives (ethinylestradiol and levonorgestrel), glipizide, tolbutamide, midazolam. Simultaneous use of cimetidine and ezetimibe does not affect the bioavailability of ezetimibe.

Antacids: simultaneous administration of antacids reduces the rate of absorption of ezetimibe, but does not affect its bioavailability. This decrease in the rate of absorption is not considered to be clinically significant.

Colestirstype: simultaneous reception of colestyramine reduces the average value AUC of total ezetimibe by approximately 55%. The effect of an additional decrease in the concentration of LDL cholesterol by the simultaneous use of ezetimibe and colestyramine can be reduced by this interaction.

Cyclosporine: in patients who underwent kidney transplantation, with SC more than 50 ml / min, taking ciclosporin in a constant dose, a single dose of Ezetrol® at a dose of 10 mg led to an increase in the value AUC the total ezetimibe averaged 3.4 times (2.3 to 7.9 times) as compared with this indicator in healthy volunteers. In one patient after kidney transplantation and with severe renal insufficiency (KK 13.2 ml / min / 1.73 m²), who took complex therapy, including ciclosporin, there was a 12-fold increase in the concentration of total ezetimibe compared with the control group. In a cross-sectional study with two periods involving 12 healthy volunteers taking 8 days ezetimibe in a dose of 20 mg once a day with a single dose of 100 mg of cyclosporine on the 7th day of ezetimib therapy, an increase in the value AUC cyclosporine an average of 15% (from a decrease of 10% to an increase of 51%) compared with this indicator in healthy volunteers who took ciclosporin once in a dose of 100 mg in monotherapy (see WITH CAUTION).

Fibrates: safety and effectiveness of the use of ezetimibe simultaneously with fenofibrate were evaluated in clinical studies (see ADVERSE EFFECTS). Safety and efficacy of ezetimibe at the same time from other fibrates have not been studied. Fibrates may increase the secretion of cholesterol from bile, which can lead to cholelithiasis. In preclinical research on dogs ezetimibe increased the concentration of cholesterol in the bile. Although the significance of these data is not yet known to humans, simultaneous use of Ezetrol® with fibrates (with the exception of fenofibrate) is not recommended until additional data are obtained from clinical trials. Simultaneous administration of Ezetrol® and fenofibrate or gemfibrozil increases the concentration of total ezetimibe by approximately 1.5 and 1.7 times, respectively, but these increases are not considered clinically significant.

Statins: with the simultaneous administration of ezetimibe with atorvastatin, lovastatin, pravastatin, simvastatin, fluvastatin and rosuvastatin clinically significant

no pharmacokinetic interactions were observed.

Indirect anticoagulants: simultaneous use of ezetimibe at a dose of 10 mg per day and warfarin had no significant effect on the bioavailability of warfarin and prothrombin time in a study involving 20 healthy volunteers. In the post-marketing period, there were reports of an increase in the International Normalized Relationship (INR) in patients taking both ezetimibe with warfarin or fluindione. These patients also took other medicines (see SPECIAL INSTRUCTIONS).

Special instructions:

Before starting treatment, patients should go to the appropriate lipid-lowering diet and continue to follow this diet during the entire period of therapy with Ezetrol®.

If the drug Ezetrol® is prescribed in combination with statin or fenofibrate, you should carefully read the instructions for the use of an additional drug.

Enzymes of the liver

In controlled clinical trials with concomitant use of Ezetrol® and statin in patients, a gradual increase in the activity of "hepatic" transaminases (3 or more times higher than ULN) was observed. If Ezetrol® is prescribed in combination with statin, liver function monitoring should be performed at the beginning of the treatment and further in accordance with the recommendations for this statin (see ADVERSE EFFECTS).

In a controlled clinical trial involving patients from chronic kidney disease, the frequency of a gradual increase in the activity of "hepatic" transaminases (3 or more times higher than ULN) was 0.7% in the group of patients taking the combined lipid-lowering drug from fixed doses of ezetimibe (10 mg) and simvastatin (20 mg) once a day, and 0.6% in the placebo group (see ADVERSE EFFECTS).

Skeletal musculature

In clinical studies, the incidence of myopathy or rhabdomyolysis associated with the use of Ezetrol® did not exceed that of the corresponding control group (placebo or statin), but myopathy and rhabdomyolysis are known undesirable reactions of statins and other lipid lowering agents.In clinical studies, the frequency of increase in CKK activity (more than 10 times higher than HHV) was 0.2% in the ezetimibe group compared with 0.1% in the placebo group and 0.1% in the concomitant use of ezetimibe and statin versus 0 , 4% in the statin monotherapy group.

In the post-marketing period of the use of Ezetrol®, reports were received of cases of development of myopathy and rhabdomyolysis, regardless of the cause of their development. Most patients who developed rhabdomyolysis received statins before starting Ezetrol®. However, very rarely reported development of rhabdomyolysis with the use of Ezetrol® in monotherapy and with the simultaneous use of Ezetrol® and medications, the use of which is known to be associated with an increased risk of rhabdomyolysis.

All patients who are prescribed Ezetrol® should be

the risk of developing myopathy and rhabdomyolysis and should inform the doctor of any unexplained muscle pain, soreness, or weakness. If myopathy

is diagnosed or suspected, the use of Ezetrol® and any statin,

taken simultaneously with the drug Ezetrol®, should be immediately stopped. The presence of these symptoms and increased activity of CK (more than 10 times higher than UGN) indicates the development of myopathy.

In a controlled clinical trial involving patients with chronic kidney disease, the incidence of myopathy / rhabdomyolysis was 0.2% in the group of patients taking a combined lipid-lowering drug with fixed doses of ezetimibe (10 mg) and simvastatin (20 mg) once a day, and 0 , 1% in the placebo group (see ADVERSE EFFECTS).

Liver failure

Because the consequences of the increased value AUC of total ezetimibe are unknown, Ezetrol® is not recommended for patients with moderate to severe hepatic impairment (see PHARMACOLOGICAL PROPERTIES, Pharmacokinetics in specific patient groups; CONTRAINDICATIONS).

Fibrates

The safety and efficacy of using ezetimibe simultaneously with fibrates (with the exception of fenofibrate) has not been established. The simultaneous use of ezetimibe with fibrates (with the exception of fenofibrate) is not recommended (see INTERACTION WITH OTHER DRUGS).

Fenofibrate

Patients receiving fenofibrate simultaneously with the drug Ezetrol®, should be warned about the possible risk of gallstone disease and gallbladder disease. If the doctor assumes the possible development of the above diseases in the patient, it is necessary to conduct a study of the gallbladder and prescribe an alternative lipid-lowering therapy (see ADVERSE EFFECTS and instructions for the use of fenofibrate).

Cyclosporin

When prescribing ezetimibe to patients receiving ciclosporin, you should follow the precautionary measures. It is necessary to regularly monitor the concentration of cyclosporine in the blood plasma while using Ezetrol® and cyclosporine (see Cautiousness, Interaction with Other Drugs).

Indirect anticoagulants

With simultaneous use of Ezetrol® with indirect anticoagulants, including warfarin or fluindione, it is necessary to monitor the values of the INR index (see INTERACTION WITH OTHER MEDICINAL DRUGS).

Effect on the ability to drive transp. cf. and fur:

There have been no studies to assess the impact on the ability to drive vehicles and work with mechanisms,however, some of the undesirable effects observed with Ezetrol® may affect the ability to drive vehicles and work with mechanisms (see ADVERSE EFFECTS).

Form release / dosage:

Tablets of 10 mg.

Packaging:

For 7, 10 or 14 tablets in PVC / Al blister. 1, 2, 3 or 4 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

Keep out of the reach of children.

Store at a temperature not exceeding 30 ° C.

Shelf life:

3 years.

Do not use the drug after the expiration date

Terms of leave from pharmacies:On prescription

Registration number:П N015754 / 01

Date of registration:04.06.2009

The owner of the registration certificate:Schering-Plau N. Labo.Schering-Plau N. Labo. Belgium

Manufacturer: & nbsp

SCHERING-PLOUGH PRODUCTS Puerto Rico

Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.

Information update date: & nbsp20.10.2015

Illustrated instructions

Instructions

Ezetrol® (Ezetrol®)