Hydrasek, capsules 100 mg 10 pcs

Pharmacological group:
Antidiarrheals. Other antidiarrheal drugs. Racecadotril.

Pharmacodynamics:
Racecadotril is an inactive substance, as a result of hydrolysis it is converted to thiorfan, which has the property of inhibiting enkephalinase, a cell membrane peptidase localized in various tissues, especially in the epithelial cells of the small intestine. This enzyme is involved in the hydrolysis of exogenous peptides and the cleavage of endogenous peptides such as enkephalins. Consequently, racecadotril protects endogenous enkephalins, which are physiologically active at the level of digestive tract, prolonging their antisecretory action.

Racecadotril is a substance with antisecretory action, its activity is limited to small intestine mucosa. It reduces hypersecretion of water and electrolytes in the small intestine caused by cholera toxin or inflammation, it has no effect on basal secretory activity. Racecadotril has a rapid antidiarrheal effect, without affecting the duration of intestinal transit.

Racecadotril does not cause abdominal bloating. In clinical studies, the incidence of secondary constipation while taking racecadotril is comparable to the group that took placebo.

When taken orally, its activity appears exclusively at the peripheral level, with no effect on the central nervous system.

Pharmacokinetics:
Absorption. Racecadotril is rapidly absorbed when administered orally. Its pharmacological action of plasma enkephalinase inhibition begins after 30 minutes. The bioavailability of racecadotril is not altered by ingestion, but peak activity comes about an hour and a half later.

Distribution. After an oral dose of 14C-racecadotril, measured radiocarbon exposure in plasma was many times higher than in hemocytes and erythrocytes and 3 times higher than in whole blood. Thus, the drug does not bind to blood cells to any significant extent. The distribution of radiocarbon in other body tissues was moderate, the average apparent volume of distribution in plasma was 66.4 kg. 90% of the active metabolite of racecadotril, thiorphan (= (RS)-N-(1-oxo-2-(mercaptomethyl)-3-phenylpropyl) glycine), binds to plasma proteins, predominantly to albumin.

The pharmacokinetic properties of racecadotril are not altered by repeated doses in adults.

The duration and severity of action of ratsecadotril are dose dependent.

In children, maximum inhibition (90%) of plasma enkephalinase activity is achieved in approximately 2 hours at a dose of 1.5 mg/kg. In adults maximum inhibition of plasma enkephalinase activity also occurs after 2 hours and corresponds to 75% inhibition at a dose of 100 mg. The duration of plasma enkephalinase inhibition is approximately 8 hours.

Metabolism. The biological half-life as measured by the duration of plasma enkephalinase inhibition is approximately 3 hours.

Racecadotril is rapidly hydrolyzed to thiorphan, the active metabolite, which in turn is converted to inactive metabolites. Repeated administration of ratsecadotril does not cause cumulation in the body. In-vitro studies indicate that ratsecadotril/tiorphan and the four major inactive metabolites do not inhibit major CYP isoenzymes (3A4, 2D6, 2C9, 1A2 and 2C19) or stimulate CYP isoenzymes (3A family, 2A6, 2B6, 2C9/2C19, 1A family, 2E1) and glucoronyltransferase-conjugated enzymes to a clinically significant degree.

Racecadotril does not affect the degree of binding to plasma proteins of active agents that bind heavily to plasma proteins, such as tolbutamide, warfarin, niflumic acid, digoxin and phenytoin.

Excretion. Racecadotril is excreted mainly in the form of inactive metabolites in the urine and in small amounts in the feces. Excretion through the lungs is insignificant.

In patients with hepatic impairment (liver cirrhosis, class B according to Child-Pugh) the following features of the pharmacokinetic profile of the active metabolite of racecadotril compared to healthy individuals were revealed: Similar values of time to reach maximum concentration (Tmax) and half-life (T1/2), and lower values of maximum concentration (Cmax) and area under the curve (AUC) (-65% and -29%, respectively).

In patients with severe renal impairment (creatinine clearance (CK) 11-39 ml/min), the kinetic profile of the active metabolite of racecadotril showed lower maximum concentrations (Cmax) (-49%) and higher area under curve (AUC) values (+16%) and half-life (T1/2), compared to healthy individuals with CK greater than 70 ml/min.

In children the pharmacokinetic parameters are similar to those in adults, the time to reach Cmax was 2 h 30 min after taking the drug. It does not accumulate after repeated doses every 8 hours for 7 days.

Indications

DiarrheaSymptomatic treatment of acute diarrhea in adults. If etiotropic treatment is possible, Hydrasek may be used as adjuvant therapy.

Active ingredient

Racecadotril

Composition

The active ingredient:

1 capsule contains: racecadotril 100 mg,.

Excipients: Lactose, corn starch pregelatinized, magnesium stearate, colloidal anhydrous silica composition of the capsule shell: iron (III) oxide yellow (E172), titanium dioxide (E171), gelatin.

How to take, the dosage

For adults from 18 years old.

The first capsule is taken regardless of the time of day. Further one capsule three times a day before meals.

The treatment should be continued until the normalization of stools (the appearance of normal stools up to two times), but no more than 7 days.

It is not recommended to use rascadotril for a long time. If after 3 days of treatment there is no improvement, you should consult a doctor.

Interaction

There are currently no data on interactions with other drugs. Loperamide or nifuroxazide have no effect on the kinetics of ratsecadotril when these drugs are used together.

Special Instructions

Use of the drug Hydrasek does not exempt from oral rehydration when it is necessary.

The presence of bloody or purulent discharge in stool and fever may be symptoms of invasive bacterial infection that caused the diarrhea or other serious disease, which is the reason for etiotropic therapy (e.g., with antibiotics) or further investigation. Monotherapy with rascadotril is contraindicated for these conditions. As an additional therapy of acute bacterial diarrhea racecadotril can be used in conjunction with antibiotics.

In connection with insufficient data it is not recommended to use racecadotril in antibiotic-associated diarrhea and chronic diarrhea.

In connection with insufficient data racecadotril should be used with caution in patients with renal and hepatic impairment.

Bioavailability of ratsecadotril may be reduced with repeated vomiting.

Effect on the ability to drive vehicles and mechanisms
Use of the drug Hydrasek has no effect or a slight effect on the ability to drive vehicles and mechanisms.

Synopsis

The pathogens that cause acute diarrhea (viruses, bacteria, toxins) damage intestinal cells, which leads to disruption of water absorption by the body. As a result, excess fluid from our body is excreted into the intestines, thinning the stool.

Racecadotril, the active ingredient in Hydrasek, protects special peptides in the intestine which regulate the release of fluid into the intestinal lumen, prolonging their action and thereby preventing the stool from becoming liquefied. Racecadotril begins to have anti-diarrheal effect within 30 minutes after intake, without slowing down intestinal motility.

Hydrasek is indicated for symptomatic therapy of acute diarrhea of any etiology (viruses, bacteria, toxins) and does not require long-term course of treatment.

Hydrasek is compatible with other medicinal agents. Racecadotril may be used together with antibiotics as additional therapy of acute bacterial diarrhea.²

Hydrasek effectively relieves symptoms of acute diarrhea in older adults; no dose adjustment is necessary for older patients.

Contraindications

Hypersensitivity to the active or any of the excipients of the drug;

congenital galactose intolerance, lactase Lapp deficiency or glucose-galactose absorption disorders;

Child and adolescent age under 18 years;

Pregnancy and lactation.

Side effects

The following adverse reactions have been reported when taking racecadotril more frequently than when taking placebo or have been reported during post-marketing use:

Nervous system disorders: frequently (> 1/100, < 1/10): headache.

Skin and subcutaneous tissue disorders: infrequent (> 1/1000, < 1/100): skin rash, erythema.

Frequency is unknown (available data are insufficient to estimate the frequency of cases): erythema multiforme, tongue edema, facial edema, lip edema, eyelid edema, angioedema, urticaria, erythema nodosa, papular rash, prurigo, skin itching, toxic dermatitis.

Overdose

There are no reports of overdose of Hydrasek. In adults, a single dose of 2 g, which is equivalent to 20 therapeutic doses, did not cause adverse effects.

Symptoms: possible increase in side effects.

Treatment: symptomatic.

Pregnancy use

Pregnancy

There are no sufficient data on the use of rascadotril in pregnant women. Animal studies have shown no direct or indirect adverse effects on pregnancy, fetal development, childbirth or postnatal development. However, due to the lack of clinical data, Hydrasek should not be used during pregnancy.

Breast-feeding
Due to the lack of information on excretion of racecadotril into breast milk Hydrasek should not be used during breast-feeding.