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

Symptomatic treatment of acute diarrhea in adults. If etiotropic treatment is possible, Hydrasec can be used as an adjuvant therapy.

Pharmacological effect

Pharmacological group:
Antidiarrheal drugs. Other antidiarrheal drugs. Racecadotril.

Pharmacodynamics:
Racecadotril is an inactive substance; as a result of hydrolysis it is converted into thiorphan, 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 breakdown of endogenous peptides such as enkephalins. Consequently, racecadotril protects endogenous enkephalins, which are physiologically active at the level of the digestive tract, prolonging their antisecretory effect.

Racecadotril is a substance with an antisecretory effect, its activity is limited to the small intestinal mucosa. It reduces hypersecretion of water and electrolytes in the small intestine caused by cholera toxin or inflammation, without affecting basal secretory activity. Racecadotril exhibits a rapid antidiarrheal effect, without affecting the duration of intestinal transit.

Racecadotril does not cause bloating. In clinical studies, the incidence of secondary constipation with racecadotril was comparable to the placebo group.

When taken orally, its activity manifests itself exclusively at the peripheral level, without affecting the central nervous system.

Pharmacokinetics:
Absorption. When taken orally, racecadotril is rapidly absorbed. Its pharmacological action by inhibiting plasma enkephalinase begins after 30 minutes. The bioavailability of racecadotril is not affected by food intake, but peak activity occurs approximately one and a half hours later.

Distribution. Following an oral dose of 14C-racecadotril, measured radiocarbon exposure in plasma was many times higher than in hemocytes and red blood cells and 3 times higher than in whole blood. Thus, the drug does not bind to blood cells to a significant extent. The distribution of radiocarbon in other body tissues was moderate, with a mean apparent volume of distribution in 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 with repeated doses in adults.

The duration and severity of the action of racecadotril are dose-dependent.

In children, maximum suppression (90%) of plasma enkephalinase activity is achieved after 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, measured by the duration of plasma enkephalinase inhibition, is approximately 3 hours.

Racecadotril is rapidly hydrolyzed to thiorphan, an active metabolite, which in turn is converted to inactive metabolites. Repeated administration of racecadotril does not cause accumulation in the body. In-vitro studies indicate that racecadotril/thiorphan 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 extent.

Racecadotril does not affect the degree of plasma protein binding of active substances that are highly bound to plasma proteins, such as tolbutamide, warfarin, niflumic acid, digoxin and phenytoin.

Excretion. Racecadotril is excreted primarily as inactive metabolites in the urine and also in small amounts in the feces. Excretion through the lungs is negligible.

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

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

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

Special instructions

The use of the drug Hydrasec does not exempt you from performing oral rehydration in cases where it is necessary.

The presence of bloody or purulent discharge in the stool and a high temperature may be symptoms of an invasive bacterial infection causing diarrhea or other serious illness, which is the basis for etiotropic therapy (for example, with the use of antibiotics) or further investigation. Monotherapy with racecadotril is contraindicated in these conditions. Racecadotril can be used in conjunction with antibiotics as adjunctive therapy for acute bacterial diarrhea.

Due to insufficient data, the use of racecadotril is not recommended for antibiotic-associated diarrhea and chronic diarrhea.

Due to insufficient data, racecadotril should be used with caution in patients with renal and hepatic impairment.

The bioavailability of racecadotril may be reduced by repeated vomiting.

Impact on the ability to drive vehicles and machinery
The use of the drug Hydrasec does not affect or has an insignificant effect on the ability to drive a car and operate machinery.

Active ingredient

Racecadotril

Composition

Active substance:

1 capsule contains: racecadotril 100 mg,.

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

Pregnancy

Pregnancy

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

Breastfeeding period
Due to the lack of information on the excretion of racecadotril into breast milk, Hydrasec should not be used during breastfeeding.

Contraindications

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

Congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption;

Children and adolescents up to 18 years of age;

Pregnancy and lactation period.

Side Effects

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

Nervous system disorders: common (> 1/100, < 1/10): headache.Skin and subcutaneous tissue disorders: uncommon (> 1/1000, < 1/100): skin rash, erythema.Frequency unknown (there is insufficient data to estimate the frequency of cases): erythema multiforme, swelling of the tongue, swelling of the face, swelling of the lips, swelling of the eyelids, angioedema, urticaria, erythema nodosum, papular rash, prurigo, pruritus, toxic dermatitis.

Interaction

Currently, there are no data on interactions with other drugs. Loperamide or nifuroxazide does not affect the kinetics of racecadotril when these drugs are used together.

Overdose

There are no reports of overdose of Hydrasec. In adults, a single dose of 2 g, equivalent to 20 therapeutic doses, did not cause a negative effect.

Symptoms: possible increased side effects.

Treatment: symptomatic.

Prescribing

Acute diarrhea

Storage conditions

At a temperature not exceeding 25 °C, out of the reach of children.

Shelf life

3 years

Manufacturer

Sofartex, France