Aquasec

Aquasec

Racecadotril

Symptomatic treatment of acute diarrhea in adults.

Inside. The first capsule at the beginning of treatment is taken regardless of the time of day. Next — 1 capsule. 3 times a day before meals. Treatment should be continued until the stool normalizes (the appearance of normal feces up to 2 times), but no more than 7 days. It is not recommended to use racecadotril for a long time.

Special patient groups

Old age. Correction of the dose of the drug for elderly patients is not required.

hypersensitivity to the active substance or any other component of the drug,

congenital galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (due to the fact that the drug contains lactose),

pregnancy,

breastfeeding period,

children under 18 years of age (due to the high content of the active substance).

The following adverse reactions were reported more frequently when taking racecadotril than when taking placebo, or were received during the post-marketing period.

From the nervous system: often (≥1/100, <1/10) — headache.

From the skin and subcutaneous tissues: infrequently (≥1/1000, <1/100) - skin rash, erythema, frequency unknown (there is not enough data available to estimate the frequency of cases) - polymorphic erythema, edema of the tongue, edema of the face, edema of the lips, edema of the eyelids, angioedema, urticaria, erythema nodosum, papular rash, prurigo, itching, toxic dermatitis.

Symptoms: currently, there are isolated cases of overdose without side effects. In adults, taking a single dose of the drug more than 2 g, equivalent to 20 times the therapeutic dose, did not cause adverse effects.

Racecadotril is a prodrug that is hydrolyzed to the active metabolite — thiorphan, which is an inhibitor of enkephalinase-a surface peptidase (located on the cell membrane), localized in various tissues, especially in the epithelium of the small intestine. This enzyme is responsible for the hydrolysis of exogenous peptides and to the breakdown of endogenous peptides such as enkephalins. As a result, racecadotril protects endogenous enkephalins, which exhibit physiological activity at the level of the digestive tract, prolonging their antisecretory effect.

Racecadotril is an intestinal antisecretory substance. It reduces intestinal hypersecretion of water and electrolytes caused by cholera enterotoxin or inflammation, and does not affect basal intestinal secretion.

Racecadotril has a rapid antidiarrheal effect, without changing the time of passage of intestinal contents through the intestine.

Racecadotril does not cause bloating.

In clinical studies, the incidence of secondary constipation when taking racecadotril was comparable to placebo.

Suction. After oral administration, racecadotril is rapidly absorbed. The time to start inhibiting plasma enkephalinase is 30 minutes. Food intake does not affect the bioavailability of racecadotril, but after eating, the activity of the drug appears with a delay of about an hour and a half.

Distribution. In the blood plasma after the use of racecadotril, labeled with a radioactive isotope ¹⁴C, the radiocarbon content was many times higher than in blood cells, and 3 times higher than in whole blood. Thus, the drug slightly binds to blood cells. Radiocarbon is moderately distributed in other tissues of the body, as evidenced by its apparent V_d in the plasma of 66.4 kg.

90% of the active metabolite of racecadotril (thiorphan) ((RS)-N (1-oxo-2-(mercaptomethyl)-3-phenylpropyl) glycine) binds to plasma proteins, mainly albumin.

The pharmacokinetic properties of racecadotril do not change as a result of repeated doses, as well as when prescribed to elderly patients.

When taking racecadotril at a dose of 100 mg, the peak inhibition time of plasma enkephalinase is approximately 2 hours and corresponds to 75% inhibition. The duration and effectiveness of racecadotril depends on the dose of the drug. In adults, the time to peak inhibition of plasma enkephalinase is approximately 2 hours and corresponds to 75% inhibition at a dose of 100 mg. The time of inhibition of plasma enkephalinase is approximately 8 hours.

Metabolism. Biological T_1/2 racecadotril, measured as the time of inhibition of plasma enkephalinase, is approximately 3 hours.

Racecadotril is rapidly hydrolyzed to thiorphan, the active metabolite, which in turn is transformed into inactive metabolites. Taking repeated doses of racecadotril does not lead to its accumulation in the body. Data obtained as a result of research in vitro, show that racecadotril/thiorphan and the 4 major inactive metabolites do not inhibit CYP isoenzymes (3A4, 2D6, 2C9, 1F2, and 2C19) to a degree that may be clinically significant.

Data obtained as a result of research in vitro, show that racecadotril / thiorphan and the 4 main inactive metabolites do not induce CYP isoenzymes (3A, 2A6, 2B6, 2C9/2C19, 1A, 2E1) and UDP-GT to a degree that may be clinically significant.

Racecadotril does not affect the protein binding of active substances such as tolbutamide, warfarin, niflumic acid, digoxin or phenytoin.

In patients with hepatic insufficiency (Child-Pugh class B), the kinetic profile of the active metabolite of racecadotril showed similar indicators._max and T_1/2 and lower C scores_max in the blood (-65%) and AUC (-29%) compared to these indicators in healthy people.

In patients with severe renal insufficiency (creatinine Cl 11-39 ml/min), the kinetic profile of the active metabolite of racecadotril showed a lower C_max (-49%) and higher AUC ( 16%) and T scores_1/2 compared to healthy volunteers (creatinine Cl >70 ml / min). C_max it is achieved after 2 hours and 30 minutes after application.

No accumulation was observed with repeated administration of the drug every 8 hours for 7 days.

Output. Racecadotril is excreted from the body in the form of active and inactive metabolites, mainly through the kidneys, and to a much lesser extent - with feces. Excretion through the lungs is insignificant.

• Antidiarrheal agent [Enkephalinase inhibitors]

Currently, there are no data on interaction with other drugs.