Otrio, tablets 10 mg 30 pcs

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

In the small intestine ezetimibe is localized in the brush border of the small intestine and prevents the absorption of cholesterol (Chs), which leads to a decrease in the intestinal Chs entry into the liver, due to which Chs stores in the liver are reduced and excretion of Chs from the blood is increased. Ezetimibe does not increase bile acid excretion (unlike drugs that bind bile acids) and does not inhibit Chs synthesis in the liver (unlike statins).

By reducing absorption of Chs in the intestine, ezetimibe reduces the entry of Chs into the liver. Statins reduce the synthesis of Chs in the liver. Due to the two different mechanisms of action, the drugs of these two classes, when prescribed together, provide an additional reduction in Chs levels.

Clinical studies have shown that elevated levels of total Chs, Chs-LDL, and apolipoprotein-B, the main protein component of LDL, contribute to the development of atherosclerosis. In addition, a decreased level of HDL-C is associated with the development of atherosclerosis. Epidemiological studies have found that cardiovascular morbidity and mortality are directly related to the level of total chs and chs-LDL and inversely related to chs-LDL. Like LDL, cholesterol- and triglyceride-rich lipoproteins, including LDL-C, LDL-C and remnants, can also contribute to atherosclerosis.

In a series of preclinical studies, ezetimibe has been shown to inhibit absorption of ¹⁴C-cholesterol and has no effect on absorption of triglycerides, fatty acids, bile acids, progesterone, ethinylestradiol, fat-soluble vitamins A and D.

Indications

Active ingredient

Composition

How to take, the dosage

Patients should follow a hypolipidemic diet before and during treatment. The recommended dose as monotherapy and in combination with statins is 10 mg once daily.

In concomitant therapy with fatty acid sequestrants, ezetimibe is used at a dose of 10 mg once daily no later than 2 hours before or no earlier than 4 hours after ingestion of fatty acid sequestrants.

Interaction

Concomitant use of antacids decreases the rate of absorption of ezetimibe, but has no effect on its bioavailability; the decrease in the rate of absorption is not clinically significant.

The AUC of total ezetimibe (ezetimibe + ezetimibe-glucuronide) is reduced by approximately 55% when used concomitantly with colestiramine. Additional decrease in LDL-C due to the addition of ezetimibe to colestyramine may be reduced by this interaction.

The 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; concomitant use is not recommended.

In kidney transplant patients with a CK greater than 50 mL/min who are continuously receiving cyclosporine, a single dose of ezetimibe at 10 mg was accompanied by an average 3.4x (2.3 to 7.9x) increase in the AUC of ezetimibe. One kidney transplant patient with severe renal failure (CK 13.2 ml/min/1.73 m2) receiving complex therapy including cyclosporine showed a 12-fold increase in ezetimibe concentration compared to the control group. Twelve healthy volunteers who received ezetimibe at a dose of 20 mg/day for 8 days concomitantly with cyclosporine at a daily dose of 100 mg showed an average 15% increase in cyclosporine AUC on day 7 (from a 10% decrease to a 50% increase) compared with patients in whom cyclosporine was used as monotherapy at a dose of 100 mg/day.

Special Instructions

Cautiously should be used in patients receiving cyclosporine; plasma concentrations of cyclosporine should be monitored with this combination.

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

Features

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

Concomitant intake of food (both high-fat and low-fat) has no effect on the bioavailability of ezetimibe when taken orally in a dose of 10 mg.

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

Ezetimibe is metabolized primarily in the small intestine and liver by conjugation with glucuronide (phase II reaction) with subsequent excretion in the bile. Minimal oxidative metabolism (phase I reaction) is observed in all studied species. Ezetimibe and ezetimibe-glucuronide are the major substances detected in plasma, accounting for approximately 10-20% and 80-90% of total plasma drug content, respectively. Ezetimibe and ezetimibe-glucuronide are slowly eliminated from plasma under conditions of intense intestinal-hepatic recirculation.

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

Contraindications

Side effects

In monotherapy: headache, abdominal pain, diarrhea.

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

In terms of laboratory parameters: possible increase in ALT and/or ACT activity ≥3×VGN (more often when combined with statins), increased CPK activity ≥10×VGN.

In clinical use:possible angioedema, skin rash, increased CPK, liver enzymes, hepatitis, thrombocytopenia, pancreatitis, nausea, myalgia; very rare – myopathy, rhabdomyolysis.

Similarities