Ezetrol tabs 10mg #28

User manual for Ezetrol tablets

Reed more and buy Ezetrol without prescription

Composition

The capsule tablet contains 10 mg of the active substance ezetimibe.
Additional components: croscarmellose Na, microcrystalline cellulose, lactose monohydrate, Mg stearate, sodium lauryl sulfate, povidone.

Form of issue

Ezetrol is available in the form of white capsule-shaped tablets. On one side the number "414" is engraved. Tablets are packed in 7/10 pieces in blisters. In a cardboard bundle can be from 1 to 4 blisters.

pharmachologic effect

The activity and effectiveness of the drug manifest only when taking per os. The main mechanism of action of the active substance differs significantly from the principle of the work of other drugs, whose action is aimed at lowering cholesterol (lipid-lowering compounds: plant sterols, fibrates, bile acid sequestrants, statins).
The active component is localized in the small intestine (in the brush border), preventing further absorption of cholesterol from the lumen of the digestive tract. The principle of action is based on increasing the excretion of cholesterol from the body and preventing its accumulation in the hepatic system in the form of stocks. The drug does not affect the processes of excretion of bile acids, which distinguishes it from drugs that bind bile acids.
Ezetrol does not inhibit the processes of synthesizing cholesterol in the liver system, which significantly distinguishes it from statins. Clinical studies for 2 weeks showed that the active substance is able to reduce absorption of cholesterol in the lumen of the intestine by 54% compared with the placebo control group (18 patients participated in the study).
With a decrease in the absorption of cholesterol from the lumen of the intestine, its stores in the liver decrease. The effect of statins is aimed at reducing the synthesis of cholesterol. Complex effects of drugs from different groups can effectively combat dyslipidemia, hypercholesterolemia, reducing the "bad" cholesterol, triglycerides, total cholesterol. There is an increase in high-density lipoproteins.
High cholesterol is one of the main causes of atherosclerotic changes inside the vessels that cause major cardiovascular diseases (angina, hypertension, myocardial infarction), strokes.
The active substance does not affect the absorption of progesterone, bile acids, fatty acids, triglycerides, fat-soluble vitamins A and D, ethinyl estradiol.

Pharmacodynamics and pharmacokinetics

Suction

Ezetimibe after ingestion of per os is rapidly absorbed from the lumen of the small intestine and is also rapidly conjugated in the hepatic system to ezetimibe-glucuronide, a phenolic pharmacologically active glucuronide. The maximum concentration of the active substance is recorded after 4-12 hours, and Cmax glucuronide earlier - after 1-2 hours. Determine the absolute bioavailability of the drug is impossible, because the compound is practically insoluble in water. When you take food (regardless of the fat content), the bioavailability of the active substance does not change with the use of Ezetrol per os in a dosage of 10 mg. The drug can be taken between meals, as well as during meals.

Distribution

The binding of glucuronide and ezetimibe to plasma proteins is 99.7% and 88-92%, respectively.

Metabolism

Metabolic processes occur in the hepatic system by conjugation with glucuronide, as well as in the small intestine. The products are excreted mainly with bile. In the blood plasma, only ezetimibe and its glucuronide are detected, which are slowly removed from the blood by enhanced hepatic intestinal recirculation. The half-life is 22 hours.

Excretion

After taking per os medication at a dosage of 20 mg, the total ezetimibe is 93% of the total radioactivity level. Radioactive traces completely disappear after 48 hours. With feces and urine, after 10 days, 78% and 11% of the total amount of active substance is excreted.

Pharmacokinetics in a special group of patients

Pediatrics

Absorbance of the active substance in children corresponds to absorption in adults. A similar situation is observed in the pharmacological parameters (based on the measurement of the total active substance). For children under 10 years of age, pharmacokinetic parameters are unknown. Clinical experience in the treatment of adolescents and children makes it possible to limit the use of medication in patients with a family form of homozygous hypercholesterolemia and sitosterolemia.

Elderly patients

In people older than 65 years, the concentration of total active substance in the blood plasma is higher than that of young people almost 2 times. The severity of cholesterol lowering effect in young and elderly people is comparable. A similar picture is observed in the safety profile of Ezetrol.

Patients with pathology of the hepatic system

A single dose of 10 mg in a patient with mild hepatic insufficiency causes an increase in the average area under AUC for the total active substance by 1.7 times in comparison with the control group of healthy volunteers. With pathology of moderate severity (according to Child-Pugh 7-9 on the scale), taking 10 mg of the drug for 2 weeks caused an increase in AUC for the total active substance by 4 times in comparison with the control group (in the 1 st and 14- th day of the study). With pathology of the liver of mild severity, no dosage is required.
It is not recommended to appoint Ezetrol to patients with severe and moderate liver disease at dosages exceeding 10 mg because of the lack of safety data.

Patients with renal pathology

In severe kidney diseases, AUC increases 1.5 times in comparison with the control group of healthy volunteers (topical for a dose of 10 mg). These indicators are not clinically important. With kidney pathology, individual dosage of the active substance is not required.

Gender identity

In females, the concentration of the active substance of ezetimibe in the blood is higher than that of men (a difference of less than 20%). The cholesterol-lowering effect is expressed equally, therefore the dosage regimen is not adjusted depending on the sex.

Indications for use

    Family form of homozygous hypercholesterolemia. Together with drugs, statins can reduce the level of total and "bad" cholesterol. Additionally, LDL-apheresis can be used.
    Primary hypercholesterolemia. The therapy is carried out together with statins (inhibitors of HMG-CoA reductase). Possible monotherapy (in addition to the cholesterol reducing diet) in patients with a family and non-family form of hypercholesterolemia.
    Homozygous form of sitosterolemia (or phytosterolemia, which is characterized by an increase in plant sterols in the blood at a high / normal level of cholesterol and an adequate index of triglycerides). In patients with familial form of homozygous sitosterolemia, ezetimibe reduces the level of campesterol and sitosterol.

Contraindications

    simultaneous therapy with fibrates (lack of data on efficacy and safety of joint application);
    individual hypersensitivity;
    moderate / severe pathology of the hepatic system (7-9 or more points on the Child-Pugh special scale).
Patients who receive Cyclosporine, ezetimibe appoint with caution.

Side effects

In combination with statins and in monotherapy, taking 10 mg of medication for 8-14 weeks in 3366 patients showed good tolerability of Ezetimibe. Negative reactions were of an easy, reversible nature.
Monotherapy: epigastric pain, headaches, diarrhea syndrome.
Combination with statins: myalgia, increased levels of AST and ALT, nausea, diarrhea syndrome, constipation, epigastric pain, fatigue, headaches, bloating. With an increase in the activity of liver enzymes, patients did not report a deterioration in their well-being; cholestasis was not recorded. Most often, patients report the following negative reactions:
    pancreatitis;
    thrombocytopenia (decrease in the number of platelets);
    skin rashes;
    angioedema;
    rhabdomyolysis;
    myopathy;
    paresthesia;
    nausea;
    hepatitis;
    increased CK.

Ezetrol, instructions for use (Method and dosage)

Reed the instruction before buy Ezetrol.
Tablets are designed for reception per os, regardless of food at any time of the day. In monotherapy and together with statins prescribe 10 mg of Ezetrol per day.
For elderly patients, individual dose selection is not carried out.
When liver failure (on the scale Child-Pugh 5-6 points), dosage adjustment is not performed.
With the severity of dysfunction of the hepatic system (according to the Child-Pugh scale more than 9 points), Ezetrol therapy is contraindicated.
With the pathology of the renal system, the treatment regimen does not change.
With simultaneous therapy with fatty acid sequestrants (FFA), medication is prescribed 4 hours after taking FFA or 2 hours prior to use.

Overdose

Several cases of drug overdose have been described in the medical literature. Most of them were not accompanied by serious symptoms, or had a short-term mild character. When poisoning, therapy is aimed at arresting the main symptoms.

Interaction

Preclinical studies have shown that the active substance is incapable of inducing cytochrome P450 enzymes that participate in drug metabolism processes. Between Ezetrol and drugs that are metabolized under the influence of N-acetyltransferase and cytochromes 2D6, P450, 1A2, 3A4, 2C9, 2C8, clinically significant drug interactions have not been identified.
With simultaneous administration of the drug does not affect the pharmacokinetic indices of Digoxin, Dexatromethorphan, Dapsone, Tolbutamide, Glipizide, Warfarin, Midazolam.
Cimetidine does not change the bioavailability of ezetimibe.

Antacid agents

Medications reduce the absorption of the active substance, without changing its bioavailability. The decrease in absorption is not clinically important.

Cholestyramine

With simultaneous admission, the mean AUC of total ezetimibe (along with glucuronide) decreases by 55%. An additional effect on reducing "bad" cholesterol may be less pronounced for this interaction.

Cyclosporin

After kidney transplantation, 10 mg of Ezetimibe resulted in a 3.4-fold increase in AUC. In a single case, a 12-fold increase was recorded. Taking 20 mg of the drug for 8 days together with Cyclosporine 100 mg resulted in an AUC increase of 15% in 12 healthy volunteers (the control group included patients taking Ciclosporin at a dose of 100 mg per day in monotherapy).

Fibrates

The simultaneous use of gemfibrozil or fenofibrate can lead to a total increase in the level of Ezetrol 1.5 and 1.7 times, respectively. However, such fluctuations are not clinically important. The effectiveness and safety of Ezetrol + fibrates are not established. Fibrates can enhance the secretion of cholesterol with bile, which can provoke the development of cholelithiasis. Preclinical studies on dogs have shown that the drug increases the cholesterol level in the gallbladder. It is not known whether this information is relevant to a person, but it is recommended not to combine Ezetimibe and fibrates.

Statins

Clinically significant drug interactions of Ezetrol with Lovastatin, Atorvastatin, Fluvastatin, Simvastatin, Pravastatin and Rosuvastatin were not observed.

Storage conditions

Transportation of tablets and their storage require a special temperature regime - up to 30 degrees.
Shelf life - 2 years.

special instructions

Before the appointment of Ezetrol patients need to go to a special lipid-lowering diet, which must be observed throughout the course of treatment. If the doctor in the therapy scheme includes statin, it is recommended that you carefully study the recommendations in the instructions of a particular statin (Atorvastatin, Rosuvastatin and others).

Liver enzymes

Controlled clinical studies have shown that with the simultaneous therapy of Ezetrol with statins, an increase in the activity of liver enzymes (three times the upper limit of normal values) is observed. If medication is prescribed together with statin, it is recommended to record ALT, AST and bilirubin at the beginning of therapy for further comparison and follow-up.

Skeletal musculature

The incidence of rhabdomyolysis and myopathy with ezetimibe in clinical trials did not exceed that in comparison with the control group (statin / placebo). Nevertheless, it is known that rhabdomyolysis and myopathy are often occurring negative reactions that occur with the use of lipid-lowering drugs, statins.

Insufficiency of the hepatic system

It is not recommended to prescribe Ezetrol at a dosage of more than 10 mg to patients with hepatic insufficiency of moderate and severe severity.

Fibrates and Ciclosporin

It is not recommended to combine fibrates with Ezetrol in the absence of data on the safety and effectiveness of joint therapy. The use of ciclosporin requires control over the level of its concentration during the administration of Ezetimibe.

In pregnancy and lactation

When bearing pregnancy, Ezetrol is not prescribed; There are no adequate studies on the safety of the use of medication in this group of patients. At the onset of pregnancy, therapy is discontinued. It is recommended to stop breastfeeding, tk. it is not known whether Ezetrol is excreted by lactation.
Studies on animals of an experimental nature did not reveal an indirect and direct negative effect of the drug on delivery, development of the embryo, the course of pregnancy, postnatal development. The introduction of statins and ezetimibe to pregnant rats did not cause the development of a teratogenic effect. The pregnant rabbits registered defects in the development of the skeletal system in the fetus.

Reviews about Ezetrol

The medication is well tolerated. Good results are achieved by observing a special lipid-lowering diet, simultaneous administration of statin drugs. Reducing cholesterol significantly reduces the risk of developing and progressing of cardiovascular diseases.