Gidrasek granules for oral suspension 10 mg, 16 sachets — Made in France — Free Delivery

Pharmacological properties

Pharmacodynamics. Racecadotril is a prodrug that requires hydrolysis to form the active metabolite of thiorphan, which is an inhibitor of enkephalinase, a cell membrane peptidase found in various tissues, especially in the epithelium of the small intestine. this enzyme promotes both the hydrolysis of exogenous and the degradation of endogenous peptides such as enkephalins. Thus, racecadotril protects endogenous enkephalins, which are physiologically active at the level of the digestive tract, prolonging their antisecretory function.

Racecadotril is an antisecretory substance that acts exclusively in the intestinal mucosa. It reduces intestinal water and electrolyte hypersecretion caused by cholera toxins or inflammation and does not affect basal secretory activity. Racecadotril exhibits a rapid antidiarrheal effect without altering the duration of intestinal transit.

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

When administered orally, the preparation exhibits exclusively peripheral activity without affecting the central nervous system.

In two clinical studies in children, racecadotril reduced stool weight during the first 48 hours by 40 and 46%, respectively. There was also a significant reduction in the duration of diarrhea and the need for rehydration.

In a meta-analysis of individual patient data (9 randomized clinical trials of racecadotril versus placebo, in addition to oral rehydration solution), individual data were collected from patients (1384 boys and girls) with acute diarrhea of ​​varying severity who were on inpatient or outpatient treatment. The mean age was 12 months (interquartile range - 6 to 39 months). Of these, 714 patients were under 1 year of age, 670 patients were over 1 year of age. The average body weight varied during the studies from 7.4 to 12.2 kg. The overall mean duration of diarrhea after enrollment was 2.81 days in the placebo group and 1.75 days in the racecadotril group. The percentage of patients who recovered was higher in the racecadotril groups compared to placebo [Hazard Ratio (HR): 2.04; 95% CI: 1.85 to 2.32; p0.001; Cox Proportional Hazards Regression]. The results were very similar for infants (1 year) (HR: 2.01; 95% CI: 1.71 to 2.36; p0.001) and preschool children (1 year) (HR: 2.16; 95 % CI: from 1.83 to 2.57; p0.001). For inpatients (n = 637), the ratio of mean stool weight in the racecadotril group to that in the placebo group was 0.59 (95% CI: 0.51 to 0.74); p0.001). For outpatients (n = 695), the ratio of mean bowel movements for diarrhea in the racecadotril group to that for diarrhea in the placebo group was 0.63 (95% CI: 0.47 to 0.85); p0.001).

Pharmacokinetics

Suction. Racecadotril is rapidly absorbed after oral administration. The initial time to inhibition of plasma enkephalinase is 30 minutes. The bioavailability of racecadotril does not change as a result of food intake, but the achievement of maximum activity is delayed by about 1.5 hours.

Distribution. After an oral dose of 14C-labeled racecadotril, the measured concentration of the radioactive carbon isotope in blood plasma was many orders of magnitude higher than in blood cells and 3 times higher than in the entire blood volume. Thus, the preparation is largely non-binding to blood cells. The distribution of the radioactive isotope of carbon in other tissues of the body is moderate, which proves the indicator of the average apparent volume of distribution in blood plasma - 66.4 kg.

90% of the active metabolite of racecadotril, thiorphan (= (RS) -N- (1-oxo-2- (mercaptomethyl) -3-phenylpropyl) glycine) binds to blood plasma proteins, mainly albumin. The pharmacokinetic properties of racecadotril do not change with repeated administration or when used in elderly patients.

The duration and extent of the action of racecadotril depend on the dose.

In children, the time to peak suppression of plasma enkephalinase is approximately 2 hours and corresponds to a suppression of 90% at a dose of 1.5 mg / kg body weight. In adults, the time to peak suppression of plasma enkephalinase is approximately 2 hours and corresponds to a suppression of 75% at a dose of 100 mg.

The duration of inhibition of plasma enkephalinase is about 8 hours.

Metabolism. The biological T½ of racecadotril, based on the degree of inhibition of plasma enkephalinase, is approximately 3 hours.

Racecadotril is rapidly hydrolyzed to thiorphan, an active metabolite, which in turn is converted to inactive metabolites.

Repeated use of racecadotril does not lead to accumulation of the compound in the body.

In vitro data indicate that racecadotril / thiorphan and 4 major inactive metabolites do not inhibit the major CYP enzyme isoforms 3A4, 2D6, 2C9, 1A2 and 2C19 to a clinically significant extent.

In vitro data indicate that racecadotril / thiorphan and 4 major inactive metabolites do not stimulate CYP enzyme isoforms (class 3A, 2A6, 2B6, 2C9 / 2C19, class 1A, 2E1) and UGT conjugating enzymes to a clinically significant extent.

Racecadotril does not affect the protein binding of active substances that are significantly associated with proteins, such as tolbutamide, warfarin, niflumic acid, digoxin or phenytoin.

In patients with impaired liver function [child-Pugh grade B cirrhosis], the kinetic profile of the active metabolite racecadotril was Tmax and T½, similar to those observed in healthy volunteers, but lower Cmax (–65%) and AUC (–29%).

In patients with severe renal impairment (creatinine clearance 11–39 ml / min), the kinetic profile of the active metabolite of racecadotril was noted with lower Cmax (-49%) and higher AUC (+ 16%) and T½ values ​​than in healthy volunteers (creatinine clearance 70 ml / min).

In children, pharmacokinetic parameters are similar to those in adults, reaching Cmax 2.5 hours after administration. No accumulation is observed after multiple doses every 8 hours for 7 days.

Excretion. Racecadotril is excreted in the form of both active and inactive metabolites. The preparation is excreted mainly by the kidneys, to a much lesser extent with feces. Pulmonary excretion is negligible.

Indications

Adjunctive symptomatic treatment of acute diarrhea in infants (from 3 months of age) and children in combination with oral rehydration and conventional supportive measures, when these measures alone are not enough to control the clinical condition, and when etiotropic treatment is not possible.

If it is possible to carry out etiotropic treatment, racecadotril can be used as an auxiliary therapy.

Application

Hydrasek is administered orally together with oral rehydration (see special instructions).

Hydrasek 10 mg is used in children weighing up to 13 kg.

The recommended dose is calculated by body weight: 1.5 mg / kg per dose. This is 1-2 sachets of the appropriate dosage, which are taken 3 times a day at regular intervals.

Children weighing up to 9 kg: 1 sachet (10 mg) 3 times a day.

Children weighing from 9 to 13 kg: 2 sachets (10 mg) 3 times a day.

Children weighing from 13 to 27 kg: 1 sachet (30 mg) 3 times a day.

Children weighing over 27 kg: 2 sachets (30 mg) 3 times a day.

In clinical trials involving children, the duration of treatment was 5 days.

Treatment should be continued until 2 cases of normal stool are recorded.

The duration of treatment should not exceed 7 days.

Long-term treatment with racecadotril is not recommended.

There have been no clinical studies involving children under 3 months of age.

Special patient groups. No study has been conducted in infants or children with renal or hepatic impairment.

The preparation should be used with caution in patients with renal or hepatic insufficiency.

Hydrasek granules can be added to food, dissolved in a glass of water or in a feeding bottle, and mixed well. Thereafter, the preparation should be used immediately.

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Due to the presence of sucrose, Hydrasek is contraindicated in patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome or sucrose-isomaltase deficiency.

Patients who develop angioedema when using ACE inhibitors should not use racecadotril.

Side effects

The following are adverse reactions to the preparation, which were observed in the racecadotril group more often than in the placebo group, or registered in the post-registration period. in terms of frequency, adverse reactions were divided into: very often (≥1 / 10), often (≥1 / 100 to 1/10), infrequently (≥1 / 1000 to 1/100), rarely (≥1 / 10,000 to 1 / 1000), very rare (1/10 000), unknown frequency (impossible to determine from the available data).

Infections and invasions: infrequently - tonsillitis.

Skin and subcutaneous tissue disorders: infrequently - rash, erythema; of unknown frequency - 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, pruritus.

Special instructions

The use of Gidrasek does not change the usual regimen for restoring water balance.

Restoring water balance is extremely important in the management of acute diarrhea in children. To restore water balance and how to achieve it, it is necessary to take into account the age and body weight of the patient, as well as the condition and severity of it, especially in the case of severe or prolonged diarrhea, accompanied by significant vomiting or loss of appetite. It is also important not to interrupt your regular meals (including breastfeeding) and to control your fluid intake.

Bloody or purulent stools and fever may indicate either the presence of invasive bacteria as the cause of diarrhea or another serious illness that requires etiotropic treatment (such as antibiotics) or further investigation. Therefore, racecadotril should not be used in such cases. Racecadotril can be used together with antibiotics in case of acute diarrhea of ​​bacterial etiology as an adjunctive therapy.

The use of racecadotril for antibiotic-induced diarrhea and chronic diarrhea is not recommended due to insufficient data.

Patients with diabetes should take into account that each sachet contains:

Hydrasek 10 mg: 0.966 g of sucrose;

Hydrasek 30 mg: 2.899 g of sucrose.

If the amount of sucrose (a source of glucose and fructose) in the daily dose of Hydrasek exceeds 5 g / day, this should be taken into account in the daily sugar diet.

The preparation should not be used in newborns under the age of 3 months, since no clinical studies have been conducted in this population.

The preparation should not be used in children with impaired renal or hepatic function of any severity due to limited information on this population.

Due to a possible decrease in bioavailability, the preparation should not be used in case of prolonged or uncontrolled vomiting.

Use during pregnancy and lactation

Pregnancy. There is no adequate data on the use of racecadotril in pregnant women. Animal studies have not shown any direct or indirect harmful effects on pregnancy, embryo-fetal development, labor, or postnatal development. However, since no specific clinical studies have been conducted, racecadotril should not be used during pregnancy.

Lactation. Due to insufficient information on the excretion of Hydrasek in breast milk, it should not be used during breastfeeding.

Children. Hydrasek, granules of 10 mg, is used in infants and children aged 3 months to 2 years.

The ability to influence the reaction rate when driving or working with other mechanisms. Racecadotril does not affect or has little effect on the ability to drive and operate machinery.

Interactions

Interactions with other preparations in humans have not been recorded to date. the simultaneous use of racecadotril with loperamide or nifuroxazide in humans does not alter the kinetics of racecadotril.

Overdose

Overdose cases have not been registered. in adults, single doses of more than 2 g, that is, 20 times higher than the therapeutic dose, did not cause negative effects.

Storage conditions

At a temperature not exceeding 25 ° c. Keep out of the reach of children.