Otrio, pills 10mg 30pcs

Composition

>of 1 tab. contains: Active ingredients:  ezetimibe – 10 mg. Auxiliary substances: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, sodium lauryl sulfate, povidone (type K 30), sodium stearyl fumarate.

Pharmacological action

Hypolipidemic agent. Selectively inhibits the absorption of cholesterol and some plant styrene in the intestine.

When entering the small intestine, ezetimibe is localized in the brush border of the small intestine and interferes with the absorption of cholesterol (cholesterol), which leads to a decrease in the intake of cholesterol from the intestine to the liver, thereby reducing the reserves of Cholesterol in the liver and increasing the excretion of Cholesterol from the blood. Ezetimibe does not increase bile acid excretion (unlike bile acid binding drugs) and does not inhibit the synthesis of cholesterol in the liver (unlike statins).

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

Clinical studies have shown that elevated levels of total cholesterol, LDL-C and apolipoprotein-B – the main protein component of LDL-contribute to the development of atherosclerosis. In addition, low HDL-C levels are associated with the development of atherosclerosis. Epidemiological studies have shown that cardiovascular morbidity and mortality are directly related to the level of total cholesterol and LDL-C and inversely related to the level of HDL-C. Like LDL, lipoproteins rich in cholesterol and triglycerides, including VLDL, HDL, 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.

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 HDL-C in patients with primary hypercholesterolemia); homozygous familial hypercholesterolemia (in combination with statins it is recommended to reduce elevated levels of total cholesterol, LDL-C, LDL-C is also possible – apheresis); homozygous sitosterolemia (or phytosterolemia) – an increased level of plant sterols in plasma with an increased or normal level of cholesterol and normal triglyceride content.

Contraindications

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

Side effects

With monotherapy:  headache, abdominal pain, diarrhea.

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

From the side of laboratory parameters:  there may be an increase in ALT and / or ACT activity ≥ 3×ULN (more often in combination with a statin), an increase in CK activity ≥10×ULN.

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

Interaction

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

When co-administered with colestyramine, the AUC of total ezetimibe (ezetimibe + ezetimibe-glucuronide) decreases by approximately 55%. Additional LDL-C reduction due to the addition of ezetimibe to colestyramine may be reduced by this interaction.

Simultaneous use 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 efficacy of ezetimibe when used with fibrates has not been established, and concomitant use is not recommended.

In kidney transplant patients with creatinine clearance greater than 50 ml / min, who are 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. One kidney transplant patient with severe renal insufficiency (creatinine clearance 13.2 ml/min/1.73 m2) receiving cyclosporine-based complex therapy showed a 12-fold increase in ezetimibe concentrations compared to the control group. In 12 healthy volunteers treated for 8 days ezetimibe at a dose of 20 mg/day concurrently with cyclosporine in a daily dose of 100 mg, on the 7th day revealed an increase in AUC of cyclosporine by 15% (from a decline of 10% to increase by 50%) compared with patients in whom cyclosporine was used as monotherapy in a dose of 100 mg/day.

How to take, course of use and dosage

Patients should follow a hypolipidemic diet before and during treatment. 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 no earlier than 4 hours after taking them.

Functional features

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

Concomitant intake of food (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 mainly metabolized in the small intestine and liver by conjugation with glucuronide (phase II reaction), followed by biliary excretion. Minimal oxidative metabolism (phase I reaction) is observed in all the studied species. Ezetimibe and ezetimibe-glucuronide are the main substances detected in blood plasma, and make up approximately 10-20% and 80-90% of the total drug content in plasma, respectively. Ezetimibe and ezetimibe-glucuronide are slowly eliminated from plasma under conditions of intensive enterohepatic recirculation.

The T_1/2 of ezetimibe and ezetimibe glucuronide is about 22 hours. Within 10 days, about 78% of the total amount of the dose taken is excreted in the feces, and about 11% in the urine.

Special instructions

Caution should be exercised 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 18 years of age.

Active ingredient

Ezetimibe

Conditions of release from pharmacies

By prescription

Dosage form

Tablets