Indications:
Complementary symptomatic treatment of acute diarrhea in infants (older than 3 months) and in children together with oral rehydration.
In case causal treatment of diarrhea is possible, racecadotril can be administered as a complementary treatment.
Administration, dosage:
Administration: The granules can be added to food or dispersed in a small amount of water (about 1 teaspoon). Mix well and give immediately to child.
Dosage:
Racedagim 10 sachet is administered via the oral route, together with oral rehydration and electrolytes (see Warnings and precautions for use).
The dose is determined according to body weight:
1.5 mg/kg per dose (corresponding to 1 to 2 sachets), 3 times daily at regular intervals.
Children under 9 kg: One 10 mg sachet, 3 times daily.
Children from 9 kg to under 13 kg: Two 10 mg sachets, 3 times daily.
Treatment should be continued until the stools return to normal.
Treatment duration should not exceed 7 days.
Long-term treatment with racecadotril is not recommended.
There are no clinical studies in infants under 3 months of age.
Special populations:
There are no studies in children with hepatic impairment or renal impairment (see Warnings and precautions for use).
Some special attention on the handling of the medicine before and after use:
There are no special requirements for handling the drug after use.
Contraindications:
Racedagim should not be administered for children who are allergic to the active substance or any composition of the excipients.
Patients who have reported angioedema with angiotensin-converting enzyme inhibitors (such as captopril, enalapril, lisinopril, perindopril, ramipril) should not use racecadotril.
Due to the presence of sucrose: This medicine should not be taken in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption syndrome or saccharase-isomaltase deficiency.
This medicine contains aspartame which is a source of phenylalanine. It may be harmful for people with phenylketonuria.
Warnings and precautions for use:
The administration of Racedagim does not modify the usual rehydration regimens.
Rehydration is very important in the management of acute diarrhea in newborns and infants. The requirement for rehydration should be adapted to the age, weight of the children and the stage, severity of the condition, specifically in case of serious or prolonged diarrhea with significant vomiting or a lack of appetite. In addition, continuous feeding is frequently (including breastfeeding) and monitoring adequate water intake is very important.
The presence of bloody or purulent stools and fever may indicate the presence of invasive bacteria or the presence of other serious disease, warranting causal (e.g., antibiotic) treatment or further investigation. Therefore, racecadotril should not be administered under these conditions. Racecadotril may be taken concomitantly with antibiotics in cases of bacterial-diarrhea as a complementary treatment.
Use of racecadotril in antibiotic-associated diarrhea and chronic diarrhea is not recommended due to insufficient data.
In chlidren with diabetes, it should be taken into account that each Racedagim 10 sachet contains 0.9265 g of sucrose.
If the quantity of sucrose (source of glucose and fructose) present in the daily dose of Racedagim 10 exceeds 5 g a day, the latter should be taken into account in the daily sugar ration.
The product must not be administered to infants less than 3 months old, as there are no clinical trials in this population.
The product must not be administered to children with renal or liver impairment, whatever the degree of severity, due to a lack of information on these patient populations.
Racedagim may cause bioavailability reduction in patients with prolonged or uncontrolled vomiting.
Skin reactions have been reported with the use of this product. These are in most cases mild and do not require treatment but in some cases they can be severe, even life-threatening. Association with racecadotril cannot be fully excluded. When experiencing severe skin reactions, the treatment has to be stopped immediately.
Pregnancy and lactation:
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 or embryo-foetal development, fertility or postnatal development.
However, since no specific clinical studies are available, racecadotril should not be administered to pregnant women.
Lactation:
Due to the lack of information regarding racecadotril excretion in human milk, racecadotril should not be administered to breastfeeding women.
Effects on ability to drive, use machines:
Racecadotril has no or negligible influence on the ability to drive and use machines.
Interactions, incompatibilities of medicine:
Interaction of the drug with other drugs and other types of interactions:
Angiotensin-converting enzyme inhibitors (such as captopril, enalapril, lisinopril, fosinopril, perindopril, ramipril) cause angioedema. This risk may be increased in presence of racecadotril.
Loperamide and nifuroxazide does not modify the kinetics of racecadotril in the body when these drugs are used concurrently.
Inform the doctor or pharmacist about all the medicines your child is taking or has recently used any other medicines including nonprescription drugs.
Incompatibilities:
Because there are no studies of drug incompatibility, do not mix this drug with other drugs.
Undesirable effects:
Like other medicines, racecadotril can cause side effects, although not everyone experiences them. If you experience any side effects not mentioned in this leaflet, or any of them worsen, inform your doctor or pharmacist.
The frequency of adverse reactions is defined using the following convention: Very common (ADR ≥ 1/10), common (1/100 ≤ ADR < 1/10), uncommon (1/1,000 ≤ ADR < 1/100), rare (1/10,000 ≤ ADR < 1/1,000), very rare (ADR < 1/10,000); not known (cannot be estimated from the available data).
Infections and infestations:
Uncommon: Tonsillitis.
Skin and subcutaneous tissue disorders:
Uncommon: Rash, erythema.
Not known: Erythema multiforme, tongue oedema, face oedema, lip oedema, eyelid oedema, angioedema, urticaria, erythema nodosum, rash papular, prurigo, pruritus.
Serious skin reactions (including angioedema) have been reported in patients on racecadotril therapy.
The incidence of these reactions is unknown but if they occur, racecadotril therapy must be discontinued and appropriate alternative therapy instituted. Patients should be aware not to take racecadotril again in these cases.
Inform your doctor about undesirable effects encountered when taking this medicine.
Overdose and management:
Overdose:
So far sporadic cases of overdose without adverse events have been reported in infants and children; ingested doses were up to 7 times the correct dose.
Management:
When an overdose occurs, supportive and symptomatic treatment is recommended.
Pharmacodynamics:
Pharmacological group: Other antidiarrheals.
ATC code: A07XA04
Racecadotril is a prodrug that needs to be hydrolyzed to its active metabolite thiorphan. Thiorphan is an inhibitor of enkephalinase, a cell membrane peptidase located in various tissues, notably the epithelium of the small intestine. This enzyme contributes both to the hydrolysis of exogenous peptides and to the breakdown of endogenous peptides such as enkephalins. Consequently, racecadotril protects endogenous enkephalins that are physiologically active at digestive tract level, prolonging their antisecretory effect.
Racecadotril is a pure intestinal antisecretory active substance. It decreases the intestinal hypersecretion of water and electrolytes induced by cholera toxins or inflammation, and does not have effects on basal secretory activity. Racecadotril exerts rapid antidiarrheal action, without modifying the duration of intestinal transit.
In two clinical studies in children, racecadotril reduced by 40% and 46%, respectively, the stool weights in the first 48 hours. A significant reduction in the duration of the diarrhea and the need for rehydration was also observed.
Racecadotril does not produce abdominal distension. During its clinical study, racecadotril produced secondary constipation at a rate comparable to placebo.
When administered via the oral route, its activity is exclusively peripheral, with no effects on the central nervous system.
Pharmacokinetics:
Absorption:
Following oral administration, racecadotril is rapidly absorbed. The initial time to plasma enkephalinase inhibition is 30 minutes.
The bioavailability of racecadotril is not modified by food, but peak activity is delayed by about one hour and a half.
Distribution:
In plasma, after an oral dose of 14C-labeled racecadotril, measured exposure of radiocarbon was many orders of magnitude higher than in blood cells and 3-fold higher than in whole blood. Thus, the drug did not bind to blood cells to any significant extent. Radiocarbon distribution in other body tissues was moderate, as indicated by the 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, mainly to albumin. The pharmacokinetic properties of racecadotril are not modified as a result of repeat dosing or administration to elderly persons.
The duration and extent of the effect of racecadotril are dose-dependent.
In children, time to peak plasma enkephalinase inhibition is approximately 2 hours and corresponds to an inhibition of 90% with the dose of 1.5 mg/kg.
In adults, time to peak plasma enkephalinase inhibition is approximately 2 hours and corresponds to 75% inhibition with the dose of 100 mg.
The duration of plasma enkephalinase inhibition is about 8 hours.
Metabolism:
The biological half-life of racecadotril, measured as plasma enkephalinase inhibition, is 3 hours approximately.
Racecadotril is rapidly hydrolysed to thiorphan, the active metabolite, which is in turn transformed into inactive metabolites. Repeated administration of racecadotril does not cause any accumulation in the body.
In the pediatric population, pharmacokinetic results are similar to those of the adult population, reaching Cmax at 2 hours 30 min after administration. There is no accumulation after multiple doses administrated every 8 hours, for 7 days.
Elimination:
Racecadotril is eliminated as active and inactive metabolites. Elimination is mainly via the urinary route, and to a much lesser extent via the fecal route. The pulmonary route is not significant.
Storage conditions, shelf life, quality specification of the medicine:
Storage conditions: Protect from humidity and light, below 300C.
Shelf life: 24 months from the manufacture date.
Quality specification: In house.
A1207002101
