Ezetrol pills 10mg №28

Pills

Composition

Each pill contains: ezetimiba -10 mg.
Excipients: sodium croscarmellose, lactose monohydrate, Magnesium stearate, microcrystalline cellulose, povidone and sodium lauryl sulfate.

Packaging

In the package of 28 pills of 10 mg labeled "414" - on the one hand.

Mechanism of action

Ezetrol - lipid-lowering drug for oral administration. 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 (cholesterol), which reduces cholesterol from the intestine to the liver, thereby reducing cholesterol in the liver and increasing the excretion of cholesterol from blood. Ezetrol does not increase the excretion of bile acids (unlike drugs that bind bile acids) and does not inhibit cholesterol synthesis in the liver (unlike statins). In a two-week clinical study that included 18 patients with hypercholesterolemia, Ezetrol reduced cholesterol absorption in the intestines by 54% compared with placebo.
By reducing the absorption of cholesterol in the intestine, ezetimibe reduces the flow of cholesterol to the liver. Statins reduce cholesterol synthesis in the liver. Due to two different mechanisms of action, the drugs of these two classes, when administered together, provide an additional reduction in cholesterol level. Ezetrol, administered in combination with statins, reduces the level of total cholesterol, LDL cholesterol, apolipoprotein-B and triglycerides and raises the level of HDL cholesterol in patients with hypercholesterolemia more than ezetimibe or Simvastatin administered separately.
Clinical studies have shown that elevated levels of total cholesterol, LDL cholesterol and apolipoprotein-B, the main protein component of LDL, contribute to the development of atherosclerosis. In addition, low HDL cholesterol is associated with the development of atherosclerosis.Epidemiological studies have established that cardiovascular morbidity and mortality are directly dependent on the level of total cholesterol and LDL cholesterol and in inverse relation to the level of HDL cholesterol. Like LDL, cholesterol and triglyceride-rich lipoproteins, including VLDL, LDPE and remnant, can also contribute to the development of atherosclerosis.
To determine the selectivity of ezetimibe in relation to inhibition of cholesterol absorption, a series of preclinical studies have been conducted. Ezetimibe inhibited the absorption of 14C-cholesterol and did not affect the absorption of triglycerides, fatty acids, bile acids, Progesterone, ethinyl estradiol, fat-soluble Vitamins A and D.

Indications and usage

- Primary hypercholesterolemia (Ezetrol is prescribed in combination with HMG-CoA reductase inhibitors (statins) or as monotherapy in addition to a diet to lower elevated levels of total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides, as well as to increase the level of HDL cholesterol in patients with primary (heterozygous familial and non-familial) hypercholesterolemia).
- Homozygous familial hypercholesterolemia (Ezetrol in combination with statins is recommended to lower elevated levels of total cholesterol, LDL cholesterol; patients may also receive additional treatment, for example, LDL-apheresis).
- Homozygous sitosterolemia (or phytosterolemia) - elevated levels of plant sterols in plasma with elevated or normal cholesterol levels and normal triglycerides (Ezetrol is recommended to reduce elevated levels of sitosterol and campesterol).

Contraindications

- Moderate (7–9 points on the Child-Pugh scale) and severe (more than 9 points on the Child-Pugh scale) degree of liver failure.
- Simultaneous use with fibrates (efficacy and safety not established)
- Hypersensitivity to the drug.
Precautions should be prescribed to patients receiving cyclosporine. When prescribing Ezetrol in combination with a statin to control contraindications, follow the instructions for use of the prescribed statin.

Pregnancy and Breastfeeding

Clinical data on the use of the drug Ezetrol during pregnancy are not available. Therefore, the use of Ezetrol during pregnancy is not recommended. In the event of pregnancy, taking Ezetrol should be discontinued. Data on the removal of ezetimiba with breast milk in women is not available. If necessary, the use of the drug during lactation should decide on the termination of breastfeeding.
In experimental studies on animals with the introduction of ezetimiba, no direct and indirect adverse effects on pregnancy, embryo / fetus development, childbirth and postnatal development were detected. When ezetimibe was administered to pregnant rats in combination with lovastatin, simvastatin, pravastatin and Atorvastatin, no teratogenic effects were observed. With the introduction of pregnant rabbits with a small frequency was observed defects in the skeleton of the fetus. Studies on rats have revealed that ezetimibe is excreted in breast milk. In this regard, Ezetrol is not recommended for use in nursing mothers.

Dosage and administration

Patients should follow a lipid-lowering diet before starting treatment and during the entire period of treatment with Ezethrol. The drug is taken orally at any time of the day, regardless of the meal. The recommended dose of Ezetrol as monotherapy or in combination with statins is 10 mg 1 time / day. Ezetrol can be taken both during and between meals.
With concomitant therapy with sequestrants of fatty acids, the drug is prescribed 10 mg 1 time / day not later than 2 hours before taking fatty acids sequestrants or not earlier than 4 hours after taking them.
Use in elderly patients
Elderly patients do not need a dose adjustment. Dose selection for patients with mild liver failure (5-6 points on the Child-Pugh scale) is not required. In patients with impaired renal function, dose selection is not required.

Special notes

It should be borne in mind that if Ezetrol prescribed in conjunction with the lipid-lowering drugs of the class of statins, it is necessary to carefully read the instructions for the medical use of this statin. When prescribing Ezetrol together with a statin, liver function monitoring should be carried out at the beginning of treatment, then in accordance with the recommendations for this statin.If necessary, the simultaneous appointment of Ezetrol with cyclosporine should monitor the concentration of the latter in the blood plasma.
In clinical studies, the incidence of myopathy or rhabdomyolysis associated with the use of Ezetrol did not exceed that compared with the corresponding control group (placebo or statin). However, myopathy and rhabdomyolysis are known undesirable side effects of statins and other lipid-lowering drugs. In clinical trials, the incidence of increased CPK (≥10xHGN) was 0.2% in the Ezetrol group compared to 0.1% in the placebo group, and 0.1% in the combined Ezethrol group with a statin, compared to 0.4% in the statin monotherapy group.
Use in pediatrics: Clinical experience with Ezetrol in children and adolescents is limited, so the drug should not be prescribed to this category of patients.

Drug Interactions

Drugs that do not affect the pharmacocokinetics of Ezetrol
Ezetrol does not induce cytochrome P450 isoenzymes. No clinically significant pharmacokinetic interaction was observed between ezetimibe and drugs that are metabolized by cytochrome P450 1A2, 2D6, 2C8, 2C9 and 3A4 isoenzymes or N-acetyltransferase.
Ezetimibe does not affect the pharmacokinetics of dapsone, dextromethorphan, Digoxin, oral contraceptives (ethinyl estradiol and levonorgestrel), glipizide, tolbutamide, midazolam and Warfarin . Simultaneous use of cimetidine with ezetimibe does not affect the bioavailability of the latter.
While taking Ezetrol with atorvastatin, simvastatin, pravastatin, lovastatin, fluvastatin and Rosuvastatin, there was no clinically significant pharmacokinetic interaction.
Drugs that affect the pharmacokinetics of Ezetrol
Simultaneous administration of antacids reduces the rate of absorption of ezetimibe, but does not affect its bioavailability and, therefore, a decrease in the rate of absorption is not clinically significant.
With simultaneous use of total ezetimibe (ezetimibe + ezetimibe-glucuronide) with colestiramine AUC, it is reduced by approximately 55%. An additional reduction in LDL cholesterol by attaching ezetimibe to colestiramine can be reduced by this interaction.
Simultaneous administration of fenofibrate or gemfibrozil increases the total concentration of ezetimibe by approximately 1.5 and 1.7 times, respectively. However, this increase is not considered clinically significant.
Safety and efficacy of ezetimibe when used with fibrates has not been established. Fibrates can increase cholesterol secretion in bile, which can lead to gallstone disease. In preclinical studies on dogs, ezetimibe increased cholesterol levels in the gallbladder. Although the significance of this data for humans is unknown, the simultaneous administration of Ezetrol with fibrates prior to clinical studies is not recommended.
In patients undergoing kidney transplantation with creatinine clearance (CC) of more than 50 ml / min, constantly receiving cyclosporine, a single dose of Ezetrol at a dose of 10 mg was accompanied by an average 3.4-fold (from 2.3 to 7.9 times) increase in AUC of ezetimibe. One patient who underwent kidney transplantation and with severe renal insufficiency (CC 13.2 ml / min / 1.73 m2), receiving complex therapy, including cyclosporine, showed a 12-fold increase in the concentration of ezetimibe, compared with the control group. In 12 healthy volunteers who received for 8 days ezetimibe at a dose of 20 mg / day concurrently with cyclosporine at a daily dose of 100 mg, on the 7th day an increase in cyclosporine AUC was found on average by 15% (from a decrease of 10% to 50%) compared with patients in whom cyclosporine was used as monotherapy at a dose of 100 mg / day.

Reported several cases of overdose, most of which were not accompanied by the occurrence of undesirable serious reactions. In clinical studies in which ezetimibe was administered to 15 healthy volunteers at a dose of 50 mg / day for 14 days, in another, 18 patients with primary hypercholesterolemia at a dose of 40 mg / day for 56 days were well tolerated.
Treatment: in case of overdose, supportive and symptomatic therapy is carried out.

At a temperature not higher than 30 ° C.