Instructions Hydrasec granules for oral suspension 30 mg sachet No. 16
Composition
active ingredient: racecadotril;
1 sachet contains 30 mg of racecadotril;
excipients: sucrose, colloidal anhydrous silicon dioxide, polyacrylate dispersion, apricot flavoring.
Dosage form
Granules for oral suspension.
Main physicochemical properties: white powder with a characteristic apricot odor.
Pharmacotherapeutic group
Drugs affecting the digestive system and metabolism. Other antidiarrheal drugs. Racecadotril. ATC code A07X A04.
Pharmacological properties
Pharmacodynamics
Racecadotril is a prodrug that requires hydrolysis to form the active metabolite thiorphan, which is an inhibitor of enkephalinase, a cell membrane peptidase found in various tissues, especially in the small intestinal epithelium. This enzyme promotes both the hydrolysis of exogenous and the cleavage of endogenous peptides such as enkephalins. Thus, racecadotril protects endogenous enkephalins, which are physiologically active in the digestive tract, prolonging their antisecretory effect.
Racecadotril is an antisecretory agent that acts exclusively in the intestinal mucosa. It reduces intestinal hypersecretion of water and electrolytes caused by cholera toxins or inflammation, without affecting basal secretory activity. Racecadotril has a rapid antidiarrheal effect without altering intestinal transit time.
Racecadotril does not cause bloating. In clinical trials, the incidence of secondary constipation with racecadotril was similar to that observed in the placebo group.
When administered orally, the drug exhibits exclusively peripheral activity, without affecting the central nervous system.
In two clinical trials in children, racecadotril reduced stool weight by 40% and 46%, respectively, in the first 48 hours. 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 patient data (1384 boys and girls) with acute diarrhea of varying severity and treated inpatiently or outpatiently were collected. The median age was 12 months (interquartile range: 6 to 39 months). Of the total, 714 patients were <1 year of age and 670 patients were >1 year of age. The mean body weight ranged from 7.4 kg to 12.2 kg during the studies. The overall mean duration of diarrhea after inclusion in the study 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; p<0.001; Cox Proportional Hazards Regression]. The results were very similar for infants (<1 year) (HR: 2.01; 95% CI: 1.71 to 2.36; p<0.001) and preschool children (>1 year) (HR: 2.16; 95% CI: 1.83 to 2.57; p<0.001). For inpatients (n=637), the ratio of mean stool weight in the racecadotril group to the mean stool weight in the placebo group was 0.59 (95% CI: 0.51 to 0.74; p<0.001). For outpatients (n=695), the ratio of the mean number of bowel movements per diarrhea in the racecadotril group to the mean number of bowel movements per diarrhea in the placebo group was 0.63 (95% CI: 0.47 to 0.85; p<0.001).
Pharmacokinetics
Absorption.
Racecadotril is rapidly absorbed after oral administration. The time to onset of plasma enkephalinase inhibition is 30 minutes.
The bioavailability of racecadotril is not altered by food intake, but the time to peak activity is delayed by approximately one and a half hours.
Distribution.
After an oral dose of 14C-labeled racecadotril, the measured concentration of the radiocarbon isotope in plasma was many orders of magnitude higher than that in blood cells and three times higher than that in whole blood. Thus, the drug does not bind to blood cells to a significant extent. Distribution of the radiocarbon isotope to other body tissues is modest, as indicated by a mean apparent volume of distribution in plasma of 66.4 kg. Ninety percent of the active metabolite of racecadotril, thiorphan ((RS)-N-(1-oxo-2-(mercaptomethyl)-3-phenylpropyl) glycine), is bound to plasma proteins, primarily albumin.
The pharmacokinetic properties of racecadotril do not change upon repeated administration or when used in elderly patients.
The duration and extent of action of racecadotril are dose-dependent.
In children, the time to peak inhibition of plasma enkephalinase is approximately 2 hours and corresponds to 90% inhibition at a dose of 1.5 mg/kg. 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 duration of inhibition of plasma enkephalinase is about 8 hours.
Metabolism.
The biological half-life of racecadotril, based on the degree of inhibition of plasma enkephalinase, is approximately 3 hours.
Repeated use of racecadotril does not lead to accumulation of the compound in the body.
In vitro data indicate that racecadotril/thiorphane and the 4 major inactive metabolites do not inhibit the major CYP enzyme isoforms 3A4, 2D6, 2C9, 1A2 and 2C19 to a clinically relevant extent.
In vitro data indicate that racecadotril/thiorphan and the 4 major inactive metabolites do not induce CYP enzyme isoforms (class 3A, 2A6, 2B6, 2C9/2C19, class 1A, 2E1) and UDP-GT (uridine-5-diphosphate glucuronyltransferase) conjugating enzymes to a clinically relevant extent.
Racecadotril does not affect the protein binding of active substances for which this binding is significant, such as tolbutamide, warfarin, niflumic acid, digoxin or phenytoin.
In patients with hepatic impairment [cirrhosis, Child-Pugh B], the kinetic profile of the active metabolite of racecadotril was characterized by Tmax and T½ values similar to those 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 characterized by a lower Cmax (-49%) and a longer AUC (+16%) and T½ than in healthy volunteers (creatinine clearance >70 mL/min).
In children, pharmacokinetic parameters are similar to those in adults, Cmax is reached 2 hours 30 minutes after administration. No accumulation is observed after multiple doses every 8 hours for 7 days.
Breeding.
Racecadotril is excreted in the form of both active and inactive metabolites. The drug is excreted mainly by the kidneys, to a much lesser extent in the feces. Pulmonary excretion is insignificant.
Indication
Adjunctive symptomatic treatment of acute diarrhea in infants (aged 3 months and older) and children in combination with oral rehydration and usual supportive measures, when these measures alone are insufficient to control the clinical condition and when etiotropic treatment is not possible.
If etiotropic treatment is possible, racecadotril can be used as an adjunctive therapy.
Contraindication
Hypersensitivity to the active substance or to any of the excipients.
Patients who have developed angioedema while taking angiotensin-converting enzyme inhibitors (such as captopril, enalapril, lisinopril, perindopril, ramipril) should not use racecadotril.
Due to the presence of sucrose, Hydrasec is contraindicated in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
Interaction with other medicinal products and other types of interactions
Increased sensitivity to the active substance or any of the auxiliary substances.
Racecadotril should not be used in patients who developed angioneurotic edema when using angiotensin-converting enzyme inhibitors (such as captopril, enalapril, lisinopril, perindopril, ramipril).
Due to the presence of sucrose, Hydrasek is contraindicated in patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency.
Application features
The use of the drug Hydrasec does not change the usual regimen for restoring water balance.
Rehydration is essential in the treatment of acute diarrhea in children. When rehydration and the method of achieving it is important to consider the patient's age and weight, as well as the stage and severity of the condition, especially in cases of severe or prolonged diarrhea accompanied by significant vomiting or loss of appetite. It is also important to maintain regular feeding (including breastfeeding) and to ensure adequate fluid intake.
Bloody or purulent stools and fever may indicate either the presence of invasive bacteria as the cause of the diarrhea or another serious illness requiring etiotropic treatment (e.g. antibiotics) or further investigation. Therefore, racecadotril should not be used in such cases. Racecadotril may be used with antibiotics in acute bacterial diarrhea as adjunctive therapy.
The use of racecadotril in antibiotic-associated diarrhea and chronic diarrhea is not recommended due to insufficient data.
Diabetics should note that each sachet contains:
Hydrasec, 10 mg granules – 0.966 g sucrose;
Hydrasec, 30 mg granules – 2.899 g of sucrose.
If the amount of sucrose (source of glucose and fructose) in the daily dose of Hydrasec exceeds 5 g per day, this should be taken into account in the daily sugar intake.
The drug should not be used in infants under 3 months of age, as clinical studies have not been conducted in this population.
The drug should not be used in children with renal or hepatic insufficiency of any severity due to limited information on this patient population.
Skin reactions have been reported with the use of the drug. In most cases, these reactions are mild and do not require treatment. However, in some cases they can be severe, even life-threatening. Their relationship to racecadotril cannot be completely ruled out. If severe skin reactions occur, treatment should be discontinued immediately.
Hypersensitivity/angioedema has been reported in patients taking racecadotril. These events may occur at any time during treatment. Patients with a history of angioedema unrelated to racecadotril may be at increased risk of developing angioedema.
Ability to influence reaction speed when driving vehicles or other mechanisms
Racecadotril has no or negligible influence on the ability to drive and use machines.
Use during pregnancy or breastfeeding
Pregnancy.
There are no adequate data from the use of racecadotril in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development. However, in the absence of specific clinical studies, racecadotril should not be used during pregnancy.
Breast-feeding.
Due to insufficient information on the excretion of Hydrasec into breast milk, it should not be used during breastfeeding.
Method of administration and doses
Hydrasec is administered orally together with oral agents to restore water balance (see section "Special instructions for use").
Hydrasec, 10 mg granules, is used in children weighing up to 13 kg.
Hydrasec, 30 mg granules, is used in children weighing 13 kg or more.
The recommended dose is calculated by body weight: 1.5 mg/kg body weight per dose. This is 1–2 sachets of the appropriate dosage, taken 3 times a day at equal intervals.
Children weighing up to 9 kg - 1 sachet (10 mg) 3 times a day.
Children weighing 9 kg to 13 kg – 2 sachets (10 mg) 3 times a day.
Children weighing 13 kg to 27 kg – 1 sachet (30 mg) 3 times a day.
Children weighing 27 kg or more – 2 sachets (30 mg) 3 times a day.
In clinical studies involving children, the duration of treatment was 5 days.
Treatment should be continued until 2 cases of normal bowel movements are recorded.
The duration of treatment should not exceed 7 days.
Long-term treatment with racecadotril is not recommended.
Clinical studies have not been conducted in children under 3 months of age.
Special patient groups
Studies in infants or children with renal or hepatic insufficiency have not been conducted (see section "Special warnings and precautions for use").
The drug should not be used in children with renal or hepatic insufficiency.
Hydrasec granules can be added to food, dissolved in a glass of water or in a feeding bottle, mixed well. The product should then be administered immediately.
Children
Hydrasec, 30 mg granules, is used for children from 2 years of age.
Overdose
Isolated cases of overdose without adverse reactions have been reported in infants and children. The doses taken were 7 times the required dose.
In adults, single doses of more than 2 g, i.e. 20 times the therapeutic dose, did not cause harmful effects.
Adverse reactions
The following are adverse drug reactions that were observed more frequently in the racecadotril group than in the placebo group or that were reported in the post-marketing period. The adverse reactions were classified by frequency as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (cannot be estimated from the available data).
Infections and infestations
Uncommon: tonsillitis.
Skin and subcutaneous tissue disorders
Uncommon: rash, erythema.
Frequency unknown: erythema multiforme, tongue edema, face edema, lip edema, eyelid edema, angioedema, urticaria, erythema nodosum, papular rash, pruritus, itching.
Severe skin reactions (including angioedema) have been reported in patients treated with racecadotril. The frequency of these reactions is unknown, but if they occur, racecadotril should be discontinued and appropriate alternative therapy instituted. In such cases, patients should be advised to avoid repeated administration of racecadotril.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
16 sachets in a cardboard box.
Vacation category
Without a prescription.
Producer
Sofartex.
Location of the manufacturer and its business address
28500, Vernouillet, rue du Pressoir, 21, France.
