Ezetrol tablets 10mg, No. 28

Primary hypercholesterolemia (in combination with statins or as monotherapy in addition to diet to reduce elevated levels of total cholesterol, LDL-C, apolipoprotein B and triglycerides, as well as to increase the level of HDL-cholesterol in patients with primary hypercholesterolemia); homozygous familial hypercholesterolemia (in combination with statins, it is recommended to reduce the elevated level of total cholesterol, LDL cholesterol, it is also possible to use LDL apheresis); homozygous sitosterolemia (or phytosterolemia) - an increased level of plant sterols in plasma with an increased or normal level of Xc and a normal level of triglycerides.

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

Before and during treatment, patients should follow a lipid-lowering diet. The recommended dose as monotherapy and in combination with statins is 10 mg 1 time / day.

With concomitant therapy with fatty acid sequestrants, ezetimibe is used at a dose of 10 mg 1 time / day no later than 2 hours before taking fatty acid sequestrants or not earlier than 4 hours after taking them.

Ezetimibe - 10 mg

Excipients: lactose monohydrate, microcrystalline cellulose, povidone, croscarmellose sodium, sodium lauryl sulfate, magnesium stearate.

Moderate (7-9 points on the Child-Pugh scale) and severe (> 9 points on the Child-Pugh scale) degree of liver failure; simultaneous use with fibrates (efficacy and safety have not been established); hypersensitivity to ezetimibe.

Clinical and pharmacological group: Lipid-lowering drug

Pharmaco-therapeutic group: Lipid-lowering agent - cholesterol absorption inhibitor

pharmachologic effect

Lipid-lowering agent. Selectively inhibits the absorption of cholesterol and some plant styrenes in the intestine.

When it enters the small intestine, ezetimibe is localized in the brush border of the small intestine and prevents the absorption of cholesterol (Xc), which leads to a decrease in the flow of Xc from the intestine to the liver, due to this, the reserves of Xc in the liver and increases the excretion of Xc from the blood. Ezetimibe does not increase the excretion of bile acids (unlike drugs that bind bile acids) and does not inhibit the synthesis of Xc in the liver (unlike statins).

By reducing the absorption of Xc in the intestine, ezetimibe reduces the flow of Xc to the liver. Statins reduce the synthesis of Xc in the liver. Due to two different mechanisms of action, drugs of these two classes, when administered together, provide an additional decrease in the level of Xc.

Clinical studies have shown that an increased level of total cholesterol, cholesterol-LDL and apolipoprotein-B - the main protein component of LDL - contributes to the development of atherosclerosis. In addition, a decreased level of HDL-C is associated with the development of atherosclerosis. In epidemiological studies, it was found that cardiovascular morbidity and mortality are in direct proportion to the level of total cholesterol and LDL-C and inversely to the level of HDL-cholesterol. Like LDL, cholesterol and triglyceride-rich lipoproteins, including VLDL, LDL, and remnants, can also contribute to the development of atherosclerosis.

A series of preclinical studies have shown that ezetimibe inhibits the absorption of 14C-cholesterol and does not affect the absorption of triglycerides, fatty acids, bile acids, progesterone, ethinyl estradiol, fat-soluble vitamins A and D.

Pharmacokinetics

After oral administration, ezetimibe is rapidly absorbed and intensively conjugated in the small intestine and liver to form a pharmacologically active phenolic glucuronide (ezetimibe-glucuronide). Cmax of ezetimibe-glucuronide is achieved after 1-2 hours, ezetimibe - after 4-12 hours. The absolute bioavailability of ezetimibe cannot be determined, since this compound is practically insoluble in water.

Concomitant food intake (both high-fat and low-fat) does not affect the bioavailability of ezetimibe when taken orally at a dose of 10 mg.

Plasma protein binding of ezetimibe and ezetimibe-glucuronide is 99.7% and 88-92%, respectively.

Ezetimibe is metabolized mainly in the small intestine and liver by conjugation with glucuronide (phase II reaction), followed by excretion in the bile. The minimum oxidative metabolism (phase I reaction) is observed in all studied species. Ezetimibe and ezetimibe-glucuronide are the main substances detected in blood plasma, and account for approximately 10-20% and 80-90% of the total drug content in plasma, respectively. Ezetimibe and ezetimibe-glucuronide are slowly excreted from plasma under conditions of intense enterohepatic recirculation.

T1 / 2 of ezetimibe and ezetimibe-glucuronide is about 22 hours. Within 10 days, about 78% of the total dose taken is excreted in the feces, and about 11% in the urine.

Indications

Primary hypercholesterolemia (in combination with statins or as monotherapy in addition to diet to reduce elevated levels of total cholesterol, LDL-C, apolipoprotein B and triglycerides, as well as to increase the level of HDL-cholesterol in patients with primary hypercholesterolemia); homozygous familial hypercholesterolemia (in combination with statins, it is recommended to reduce the elevated level of total cholesterol, LDL cholesterol, it is also possible to use LDL apheresis); homozygous sitosterolemia (or phytosterolemia) - an increased level of plant sterols in plasma with an increased or normal level of Xc and a normal level of triglycerides.

Dosage regimen

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

Before and during treatment, patients should follow a lipid-lowering diet. The recommended dose as monotherapy and in combination with statins is 10 mg 1 time / day.

With concomitant therapy with fatty acid sequestrants, ezetimibe is used at a dose of 10 mg 1 time / day no later than 2 hours before taking fatty acid sequestrants or not earlier than 4 hours after taking them.

Side effect

With monotherapy: headache, abdominal pain, diarrhea.

In combination therapy with a statin: headache, fatigue, abdominal pain, constipation, diarrhea, bloating, nausea, increased AST and ALT activity, myalgia.

On the part of laboratory parameters: is it possible to increase the activity of ALT and / or ACT? 3? VGN (more often when combined with a statin), increased activity of CPK? 10? VGN.

When used in clinical practice: possible angioedema, skin rash, increased CPK, liver enzymes, hepatitis, thrombocytopenia, pancreatitis, nausea, myalgia; very rarely - myopathy, rhabdomyolysis.

Contraindications for use

Moderate (7-9 points on the Child-Pugh scale) and severe (> 9 points on the Child-Pugh scale) degree of liver failure; simultaneous use with fibrates (efficacy and safety have not been established); hypersensitivity to ezetimibe.

Application during pregnancy and lactation

Adequate and strictly controlled studies on the safety of ezetimibe during pregnancy have not been carried out, therefore the use in this category of patients is not recommended. If pregnancy occurs, ezetimibe should be discontinued.

It is not known whether ezetimibe is excreted in human breast milk. If necessary, use during lactation should decide on the termination of breastfeeding.

In experimental studies on animals with the introduction of ezetimibe, there was no direct or indirect adverse effect on the course of pregnancy, embryo / fetal development, childbirth and postnatal development. No teratogenic effects were observed when ezetimibe was administered to pregnant rats in combination with lovastatin, simvastatin, pravastatin and atorvastatin. When administered to pregnant rabbits, fetal skeletal defects were noted with a low frequency. It has been established that ezetimibe is excreted in breast milk in lactating rats.

Application for violations of liver function

Contraindicated in moderate (7-9 points on the Child-Pugh scale) and severe (> 9 points on the Child-Pugh scale) degree of liver failure. Preparations containing eucalyptol are not used rectally for liver dysfunctions.

Application for impaired renal function

Preparations containing eucalyptol are not used rectally for renal impairment.

Application in children

Ezetimibe should not be used in children and adolescents under the age of 18.

special instructions

Use with caution in patients receiving cyclosporine; with this combination, the concentration of cyclosporine in the blood plasma should be monitored.

Ezetimibe should not be used in children and adolescents under the age of 18.

Drug interactions

Concomitant use of antacids reduces the rate of absorption of ezetimibe, but does not affect its bioavailability; a decrease in the rate of absorption is not clinically significant.

With simultaneous use with cholestyramine, the AUC of total ezetimibe (ezetimibe + ezetimibe-glucuronide) decreases by approximately 55%. An additional decrease in LDL-C due to the addition of ezetimibe to cholestyramine can be reduced by this interaction.

Concomitant administration of fenofibrate or gemfibrozil increases the total concentration of ezetimibe by approximately 1.5 and 1.7 times, respectively (this increase is not considered clinically significant).

The safety and effectiveness of ezetimibe when used with fibrates has not been established, and concomitant use is not recommended.

In patients who underwent kidney transplantation, with CC more than 50 ml / min, constantly receiving cyclosporine, a single dose of ezetimibe at a dose of 10 mg was accompanied by an average 3.4-fold (from 2.3 to 7.9 times) increase in the AUC of ezetimibe. In one patient who underwent kidney transplantation and with severe renal failure (CC 13.2 ml / min / 1.73 m2), who received complex therapy, including cyclosporine, there was a 12-fold increase in the concentration of ezetimibe compared with the control group. In 12 healthy volunteers who received ezetimibe at a dose of 20 mg / day for 8 days simultaneously with cyclosporine at a daily dose of 100 mg, on the 7th day, an increase in the AUC of cyclosporine by an average of 15% (from a decrease by 10% to an increase by 50%) compared with patients in whom cyclosporine was used as monotherapy at a dose of 100 mg / day.