Ezetrol

Pharmacological action

One tablet of Ezetrol contains 10 mg of active ingredient – эзетимиб. As excipients are used: cellulose microcrystallic, sodium lauryl sulfate, povidone, magnesium stearate, croscarmellose sodium, lactoses monohydrate.

Ezetrol treats group of hypolipidemic drugs. Drug is intended for reception inside. The mechanism of effect of drug differs from other analogs of Ezetrol from a hypolipidemic class of drugs, such as statines, fibrata and stirola of a plant origin. At hit in a small intestine drug concentrates in a brush border of small bowels and creates a hindrance to cholesterol absorption, reducing intake of cholesterol in a liver at the expense of what in a liver its concentration goes down.

Ezetrol influences increase in excretion of bile acids. By results of two-week clinical testing in which 18 patients participated it was established that Ezetrol's acceptance reduced absorption of cholesterol by 54%. Thus, the probability of development of atherosclerosis decreases. By researches it is established that the mortality caused by cardiovascular diseases is in direct dependence on the general level of cholesterol, according to its decrease lowers incidence and mortality.

Ezetrol's pharmacokinetics

After oral administration Ezetrol is quickly soaked up in a small bowel and a liver, forming pharmacological active phenolic glucuronide. The maximum concentration of a glucuronide in a blood plasma comes in 1-2 hour, an ezetimib – in 5-12 hours. Due to almost full insolubility of drug in water it is impossible to define its absolute bioavailability.

At a standard single dose in 10 mg, the concomitant use with food does not affect on Ezetrol's bioavailability. Drug contacts blood proteins for 99.7%

Ezetrol's metabolism happens generally in a liver and a small bowel by conjugation (reaction of the II phase) to a glucuronide. Drug is removed with bile.

At intake of 20 mg of drug of a marked 14C-ezetimib, the level of an ezetimib in a blood plasma made 93% of blood plasma radioactivity. On coming of 48 hours, radioactive traces in a blood plasma it was revealed not. Ezetrol elimination half-life approximately makes 22 hours. About 78% are brought out of total quantity of a dose, within 10 days, with urine about 11%, with a stake.

Data on pharmacokinetics at children up to 10 years are absent. Indicators of metabolism and absorption of drug at adults and teenagers from 10 to 18 years identical.

Patients with a slight liver failure do not have need to select an individual dosage. At women is slightly higher, approximately for 20%, concentration of drug in a blood plasma, than at men.

Indications

• homozygous sitosterolemiya;
• primary hypercholesterolemia;
• homozygous family hypercholesterolemia.

Ezetrol's contraindications

• Liver failure (moderate and heavy);
• lactose intolerance;
• hypersensitivity to drug components;
• age up to 18 years.

It is necessary to show care at purpose of drug to the patients accepting cyclosporine. It is not recommended to accept Ezetrol's analogs along with fibrata, before data acquisition about results of clinical trials.

Ezetrol's dosage

Prior to the beginning of a course of treatment Ezetrol patients should keep to the hypolipidemic diet directed to decrease in cholesterol. It is possible to accept Ezetrol regardless of meal.

The dose recommended by Ezetrol's instruction both for monotherapy, and at a combination to statines – 10 mg a day.

Patients with easy disturbances of functions of kidneys or to a liver and elderly patients do not need an individual dosage. At an average or heavy liver failure Ezetrol's reception is not recommended.

Overdose

From the comments received about overdose by Ezetrol it is established that in most cases the overdose is not followed by undesirable reactions, and at their emergence they have not expressed and fulminating character.

At overdose by Ezetrol, the instruction it is recommended to carry out the supporting and symptomatic therapy.

Ezetrol's interaction with other drugs

Ezetrol does not influence pharmacokinetics of oral contraceptives (levonorgestrel and ethinylestradiol), dapsone, a glipizid, midazolam, Tolbutamidum, dextromethorphan, warfarin and digoxin.

The combination to Cimetidinum does not influence its bioavailability.

At a concomitant use with antacids the speed of absorption decreases, without exerting impact on its bioavailability.

The combination of reception of Ezetrol with gemfibrozily and fenofibraty increases total concentration of drug at 1.5-1.7 time.

There are no data on safety of a concomitant use about fibratam which can increase releases of cholesterol therefore there can be cholelithiasis. Therefore purpose at the same time of Ezetrol's analogs and fibrat is not recommended.

Clinically significant pharmacokinetic interaction of Ezetrol with rozuvastatiny, fluvastatiny, lovastatiny, pravastatiny, simvastatiny and atorvastatiny was not revealed.

Pregnancy and lactation

About results of use by pregnant women of Ezetrol of responses it was not received therefore during pregnancy Ezetrol's use by the instruction is not recommended. When determining the beginning of pregnancy use of drug should be stopped.

About Ezetrol's removal with breast milk there are no data therefore it is recommended to stop breastfeeding prior to administration of drug.

Side effects of Ezetrol

During clinical tests lasting up to 14 weeks in which 3366 patients took part good tolerance of drug at daily reception of 10 mg in a combination with statines was established or as monotherapy. Easy and quickly passing side effects were recorded, the frequency of side effects did not differ from frequency at the group accepting placebo.

At monotherapy, the following side effects are possible: diarrhea, abdominal pain, headache.

At Ezetrol's combination and statine can be shown: mialgiya, nausea, abdominal distention, diarrhea, lock, abdominal pain, fatigue, headache.

The comments received about a clinical use of Ezetrol showed a possibility of development of the following reactions: paresthesias, nausea, pancreatitis, skin rash, thrombocytopenia, a Quincke's disease, it is rare – a rabdomioliza, myopathies.

Storage conditions

Drug is stored in the place unavailable to children at the room temperature.